bluuebunny/crossref_metadata_2025 huggingface dataset:
Nebulised Dexmedetomidine versus Nebulised Lignocaine in Blunting the Haemodynamic Response to Laryngoscopy and Endotracheal Intubation: A Randomised Control Study
Authors: Rani Anju , Ahlawa Geeta , Kumar Amit , Kshetrapal Kirti , Ahlawat Mangal , Bala Renu
Published: June 2024

Introduction: Direct laryngoscopy followed by intubation induces a stress response leading to haemodynamic changes that are often transient, unpredictable, and variable. Both dexmedetomidine and lignocaine have been used in nebulised form successfully to blunt haemodynamic stress response, but they have never been compared previously. Aim: To compare nebulised dexmedetomidine and nebulised lignocaine in blunting the haemodynamic response to laryngoscopy and endotracheal intubation. Materials and Methods: This randomised, double-blinded study was conducted on 135 patients with American Society of Anesthesiologists (ASA) physical Status I and II, aged 18 to 60 years, planned for surgery under general anaesthesia with endotracheal intubation. Patients were divided into three groups of 45 each using a computer-generated random number table. Patients in group D were nebulised with dexmedetomidine 1 μg/ kg, with lignocaine 1.5 mg/kg in group L, and with normal saline in group C. The primary objective was to compare nebulised dexmedetomidine and nebulised lignocaine in blunting the haemodynamic response to laryngoscopy and endotracheal intubation with respect to Heart Rate (HR), Systolic Blood Pressure (SBP), Diastolic Blood Pressure, and Mean Arterial Pressure (MAP). The secondary objective was to study sideeffects associated with the use of nebulised dexmedetomidine and lignocaine. Results: The demographic profile was found to be comparable in all three groups. The mean age was 40.44±11.77 years, 40.04±12.33 years, and 42.89±11.57 years in group D, group L, and group C, respectively, with a p-value of 0.4. The rise in HR during intubation and at all later time points was found to be less in group D and group L compared to group C. Additionally, the rise in HR was found to be higher in group L compared to group D. Similarly, the attenuation effect on SBP and Diastolic Blood Pressure (DBP) was greater in group D patients. Conclusion: Both nebulised dexmedetomidine and lignocaine were effective in attenuating the pressor response during laryngoscopy and intubation, with dexmedetomidine being more effective than lignocaine without any adverse haemodynamic effects.
Occupational Exposure to Blood and Body Fluids among Healthcare Workers at a Tertiary Care Teaching Hospital: A Retrospective Observational Study
Authors: Modi Chirag , Patel Naimika , Desai Roshani , Shah Purvi , Vyaskar Neela , Thakor Ankit
Published: June 2024

Introduction: Occupational exposure to Blood and Body Fluids (BBFs) through Needlestick Injuries (NSIs) or mucosal exposure can lead to the transmission of Blood-borne Viruses (BBVs). Such exposures require a robust reporting system followed by a detailed analysis of their root causes. Aim: To assess occupational exposure incidences and their epidemiological characteristics among Healthcare Workers (HCWs). Materials and Methods: A retrospective observational study was conducted in the Department of Microbiology, Pramukhswami Medical College and Shree Krishna Hospital, Karamsad, Anand, Gujarat, India. Data regarding the distribution of exposures, the cadre of HCWs involved, the location in the hospital, and Hepatitis B vaccination status were collected by the Hospital Infection Control Committee (HICC) from January 2012 to December 2022. The data analysis was performed in 2023 using Microsoft Excel 2013. The incidence of exposures was calculated as exposures per 1000 inpatient-days, which is the number of accidental exposures per year divided by inpatient days (the sum of the number of inpatients present on each day of that year) multiplied by 1000. Results: A total of 750 exposures occurred with an incidence density of 0.52 per 1000 patient-days. Nurses, 305 (40.7%) were the most common HCWs affected. The critical care unit, 189 (25.2%) had the highest incidence of exposures. Phlebotomy, 165 (22%) followed by recapping, 140 (18.7%) were the most common modes of exposure. The source was positive for BBVs in 119 (15.8%) cases, whereas it was unknown in 35 (4.6%) cases. Among them, 60 (8%) exposed HCWs had never been vaccinated with the Hepatitis B vaccination. Conclusion: Accidental exposures continue to be an important occupational health hazard among HCWs, especially nurses. Periodic awareness programs and training to prevent exposures, their reporting, and ongoing data analysis shall help in reducing the incidence of these exposures.
ИССЛЕДОВАНИЕ ПЛАНЕТ-ГИГАНТОВ МЕЖПЛАНЕТНЫМИ КОСМИЧЕСКИМИ АППАРАТАМИ
Authors: Петрухин А.А. , Емельянов Н.В.
Published: June 2024

Наша Солнечная система включает восемь планет, множество комет, астероидов, метеороидов и межпланетную среду. За четырьмя планетами земной группы в порядке удаления от Солнца следуют четыре планеты-гиганта: Юпитер, Сатурн, Уран и Нептун. В этой статье будет рассказано об исследовании планет-гигантов, их колец и спутников с помощью межпланетных космических аппаратов. Эти грандиозные исследования начались в 70-х годах прошлого века и продолжаются до сих пор. Планируются новые космические миссии, ставятся новые задачи по исследованию внешней Солнечной системы.
Assessment of Biodegradation and Phytotoxicity of Azo Dyes Methyl Orange and Crystal Violet by Escherichia coli and Bacillus subtilis
Authors: EI Okoh , OM Immanuel
Published: June 2024

Azo dyes are widely used colourants, possess array of colours and are generally recalcitrant to microbial degradation. This study aimed to isolate azo dyes degrading bacteria from soil; treat methyl red and crystal violet dyes using the isolates, and assess the phytotoxicity of the treated and untreated dyes on sorghum. Ten bacteria were isolated from the soil, of which two were identified as efficient azo dyes degrading bacteria by efficiency in dye decolouration. The isolates were identified as Escherichia coli and Bacillus subtilis based on their biochemical characteristics. The isolates were able to degrade methyl orange dye by 16-75 % and crystal violet by 16-78%, depending on the concentration of the dye. The isolates were more efficient at degrading the dyes at a low concentration of 0.00025 mg/ml, as indicated by a higher percentage of decolourization (53-79%). The percentage phytotoxicity of the untreated methyl red ranged from 33-59%, while the toxicity of the untreated crystal violet ranged from 62-91%. The toxicity of the treated methyl red ranged from 9-34%, while the toxicity of the treated crystal violet ranged from 12-32%. The results revealed that the isolates were capable of degrading methyl red and crystal violet dyes, and could be useful in the bioremediation of azo dyes polluted soil.
The last word in strong correlations
Authors: Shankar R.
Published: September 2011

In the Fractional Quantum Hall Effect (FQHE), in the noninteracting limit, only a fraction ν of the Lowest Landau Level (LLL) is occupied, producing a huge degeneracy. Interactions lift this degeneracy and mix in higher LL's. In the limit in which we ignore all but the LLL (i.e., let the inverse electron mass 1/m → ∞), the kinetic energy is an irrelevant constant and the ratio of potential to kinetic energy is essentially infinite, making this the most strongly correlated problem imaginable. I give a telegraphic review of the Hamiltonian Theory of the FQHE developed with Ganpathy Murthy that deals with this problem with some success. A nodding acquaintance with FQHE physics is presumed.
Strong electron correlations in FeSb2
Authors: Sun P. , Søndergaard M. , Iversen B.B. , Steglich F.
Published: September 2011

FeSb2 has been recently identified as a new model system for studying many‐body renormalizations in a d‐electron based narrow gap semiconducting system, strongly resembling FeSi. The electron‐electron correlations in FeSb2 manifest themselves in a wide variety of physical properties including electrical and thermal transport, optical conductivity, magnetic susceptibility, specific heat and so on. We review some of the properties that form a set of experimental evidences revealing a significant role of correlation effects in FeSb2. The metallic state derived from slight Te doping in FeSb2, which exhibits a large quasiparticle mass, will also be introduced.
Superperturbation theory on the real axis
Authors: Jung C. , Wilhelm A. , Hafermann H. , Brener S. , Lichtenstein A.
Published: September 2011

In this article we formulate the superperturbation theory for the Anderson impurity model on the real axis. The resulting impurity solver allows to evaluate dynamical quantities without numerical analytical continuation by the maximum entropy method or Padé approximants. This makes the solver well suited to study multiplet effects in solids within the dynamical mean field theory. First examples including multi‐orbital problems are discussed.
Anatomy practical examinations: How does student performance on computerized evaluation compare with the traditional format?
Authors: Inuwa Ibrahim Muhammad , Taranikanti Varna , Al‐Rawahy Maimouna , Habbal Omar
Published: September 2011

Practical examinations in anatomy are usually conducted on specimens in the anatomy laboratory (referred to here as the “traditional” method). Recently, we have started to administer similar examinations online using the quiz facility in Moodle™. In this study, we compare student scores between two assessment environments viz. online and traditional environments. We hypothesized that regardless of the examination medium (traditional or online) overall student performance would not be significantly different. For the online medium, radiological images, prosected specimens, and short video clips demonstrating muscle action were first acquired from resources used for teaching during anatomy practical classes. These were optimized for online viewing and then uploaded onto Moodle learning management software. With regards to the traditional format, actual specimens were usually laid out in a circular stream. Identification tags were then attached to specific spots on the specimens and questions asked regarding those identified spots. A cohort of students taking practical examinations in six courses was studied. The courses were divided into three pairs with each pair credit‐weight matched. Each pair consisted of a course where the practical examination was conducted online and the other in the traditional format. There was no significant difference in the mean scores within each course pair. In addition, a significant positive correlation between score in traditional and online formats was found. We conclude that mean grades in anatomy practical examination conducted either online or in the traditional format were comparable. These findings should reassure teachers intending to use either format for their practical examinations. Anat Sci Educ. © 2011 American Association of Anatomists.
Collection of peripheral blood progenitor cells for autologous use: Performance enhancements of COBE spectra, auto‐PBSC
Authors: Sorensen Betina Samuelsen , Thomsen Anna‐Maria , Moller Bjarne Kuno
Published: September 2011

Collection of peripheral blood stem cells (PBSC) must be performed in a safe and effective manner. Issues like automation, collection efficiency (CE), and adverse events must be considered. Auto‐PBSC (COBE Spectra) is a fully automated program for PBSC collection. Changes in the protocol were made to achieve high CE, low product volume, and resulted in three groups of patients. Standard operating procedures (SOPs) were developed to reduce citrate toxicity and patients with central venous catheter. Twenty patients and 27 collections (Group 1), 88 patients and 112 collections (Group 2), and 158 patients and 194 collections (Group 3) were recorded. The protocol changes increased CE significantly from 31% (Group 1) to 57 and 59% (Group 2 and 3). Adjusting endpoint according to the preapheresis number of CD34+ cells reduced the collection time and the volume of the product significantly (median 227 min and 56 mL) without affecting CE. Mean level of ionized calcium before collection was 1.22 mmol/L, measured in 31 patients. This declined to a mean of 1.07 mmol/L after 1 h of collection and remained unchanged despite continuous calcium infusion. The number of patients with mild symptoms of citrate toxicity was reduced from 20 to 6%. A central venous catheter was used in 15%. Compared to peripheral access no differences in blood flow rate or time to perform the collection were found. Changes in the Auto‐PBSC protocol resulted in an improved CE and a small product. SOPs reduced the number of patients with citrate toxicity and with central venous catheter. J. Clin. Apheresis, 2011. © 2011 Wiley Periodicals, Inc.
Systematic screening of BK virus by real‐time PCR prevents BK virus associated nephropathy in renal transplant recipients
Authors: Hammarin Anna‐Lena , Öqvist Björn , Wahlgren John , Falk Kerstin I.
Published: September 2011

BK virus associated nephropathy occurs in approximately 5% of renal transplant recipients. Quantitation of BKV DNA in serum/plasma early in the course of disease has been suggested to be an important diagnostic tool for polymavirus‐associated nephropathy (PVAN). The aim of this study was to develop a BKV real‐time PCR (qPCR), which could be included in a diagnostic qPCR platform. Additionally, the significance of the assay as a surrogate marker for PVAN was investigated. Quantitation of BKV DNA by qPCR was carried out on 234 serum samples from a retrospective study including 31 renal transplant recipients monitored for at least 6 months post‐transplantation. BKV viremia was detected in 9 out of 31 patients. Four patients had a viral load of >10,000 copies/ml at least on one occasion. In two of these patients, PVAN was diagnosed clinically during the study period. In retrospect, these patients were shown to be BKV positive before the clinical diagnosis of PVAN was made. Another two patients had a permanent graft dysfunction, but were never clinically diagnosed with PVAN. None of the remaining five patients with BKV DNA (<10,000 copies/ml) had renal impairment. Based on these results, an algorithm was introduced at the study center in 2006 and to date, August 2011, no cases of PVAN with loss of graft have been observed. The concept of including different PCR protocols in a common qPCR platform allows laboratories with small sample numbers to perform regularly a variety of assays at a reasonable cost. J. Med. Virol. 83:1959–1965, 2011. © 2011 Wiley‐Liss, Inc.
Study on 1D forward modeling of marine CSEM survey
Authors: Ju Hanji , Fang Guangyou , Zhang Feng , Lin Zhiwei , Ji Yicai , Huang Ling
Published: September 2011

The two‐level discrete complex image method (DCIM) is successfully introduced into the marine controlled‐source electromagnetic (MCSEM) survey. The original integral path does not hold valid in extremely low‐frequency situation, and the reason can be ascribed to the change of wave number at different frequencies. The new integral path suitable for the extremely low‐frequency situation is proposed. This paper focuses on the selection of parameters, including the sampling space, the sampling number, and the number of exponential terms. The study shows that the effects of these parameters are different on different paths. The appropriate ranges of these parameters are proposed. In order to validate the DCIM, we calculated the electric field of a five‐layer model under different frequency situations. The electric field attenuates faster with frequency increase. The effect of oil‐layer conductivity is studied, and the results show that the electric field is stronger with lower oil conductivity. All the results accord to the physical meanings of MCSEM. The model with multiple objects is studied to find the effect of shallow resistor on the detection ability of MCSEM. Copyright © 2011 John Wiley & Sons, Ltd.
A randomized, double‐blind, placebo‐controlled trial of safinamide as add‐on therapy in early Parkinson's disease patients
Authors: Stocchi Fabrizio , Borgohain Rupam , Onofrj Marco , Schapira Anthony H.V. , Bhatt Mohit , Lucini Valentina , Giuliani Rodolfo , Anand Ravi ,   for the Study 015 Investigators
Published: September 2011

Safinamide is an α‐aminoamide with both dopaminergic and nondopaminergic mechanisms of action evaluated as an add‐on to dopamine agonist (DA) therapy in early‐stage PD. In this 24‐week, double‐blind study, patients with early PD receiving a stable dose of a single DA were randomized to once‐daily safinamide 100 mg, safinamide 200 mg, or placebo. The primary efficacy variable was UPDRS part III (motor examination) total score. Analysis was hierarchical: 200 mg of safinamide versus placebo was tested first; the success of safinamide 100 mg versus placebo was contingent on this. Two hundred sixty‐nine patients received safinamide 100 mg (n = 90), safinamide 200 mg (n = 89), or placebo (n = 90); 70, 81, and 81 patients, respectively, completed the study. Mean improvements from baseline to week 24 in UPDRS III total scores were −3.90 for safinamide 200 mg, −6.0 for safinamide 100 mg and −3.60 for placebo. The difference between safinamide 200 mg and placebo was not significant [point estimate: −0.4; 95% confidence interval (CI): −2.3–1.4; P = 0.6504]. Although the difference between 100 mg/day and placebo was significant (point estimate: −1.9; 95% CI: −3.7 to −0.1; P = 0.0419), these results are considered exploratory. No clinically meaningful differences from placebo were observed for any safety variables. This study did not demonstrate a significant improvement of the primary endpoint for safinamide 200 mg/day. Exploratory analysis of the primary endpoint for 100 mg/day demonstrated that the addition of safinamide to a stable dose of DA improves motor symptoms in early PD and warrants further investigation. © 2011 Movement Disorder Society
Micromechanical discrete element modeling of fiber reinforced polymer composites
Authors: Khattab Ahmed , Khattak Mohammad J. , Fadhil Imran M.
Published: September 2011

An analytical model of mechanical behavior of carbon fiber reinforced polymer composites using an advanced discrete element model (DEM) coupled with imaging techniques is presented in this article. The analysis focuses on composite materials molded by vacuum assisted resin transfer molding. The molded composite structure consists of eight‐harness carbon fiber fabrics and a high‐temperature polymer. The actual structure of the molded material was captured in digital images using optical microscopy. DEM was developed using the image‐based‐shape structural model to predict the composite elastic modulus, stress–strain response, and compressive strength. An experimental case study is presented to evaluate the accuracy of the developed analytical model. The results indicate that the image‐based DEM micromechanical model showed fairly accurate predictions for the elastic modulus and compressive strength. POLYM. COMPOS., 2011. © 2011 Society of Plastics Engineers
Effect of stress transfer between fiber and matrix on toughness of polymer composite
Authors: Ichinose Noriyo , Ishikawa Masaru , Morimoto Kiyoshi
Published: September 2011

Thanks to their lightweight properties, formability and low cost, polymers have become an essential material for manufactured products. To improve the mechanical properties, almost all polymers are blended with some kind of fiber made from glass, carbon, organic or natural material. The importance of interfacial strength between matrix and fiber is a well known requirement for effective mechanical properties and some experimental results indicate that low interfacial strength helps increase the toughness of composites. In this paper, models of composite reinforced by fiber aligned with maximum principal stress under uni‐tensile loading are simulated. Based on the simulation result, we discuss the effect of interfacial strength, aspect ratio of fiber and friction force between matrix and fiber on stable deformation and provide the guidelines for establishing composites with high modulus and toughness. POLYM. COMPOS. 2011. © 2011 Society of Plastics Engineers
Framework for Activity of Ethics Committees in Ukraine
Authors: Kornatsky Vasil , Talaieva Tatyana , Silantieva Olga
Published: September 2011

Ethics committee supervision is an essential part of conducting clinical trials and is required to ensure compliance with the international recommendations including the Declaration of Helsinki, International Conference on Harmonisation Good Clinical Practice (ICH GCP), Directive 2001/20/EC of the European Parliament and Council and WHO recommendations etc. No clinical trial can be initiated without prior review and approval from an ethics committee. In addition to expert evaluation of planned clinical trials, ethics committees are responsible for providing regular monitoring of clinical trial compliance with the international and national ethic, moral and legal aspects throughout the whole process of the trial conduct. Copyright © 2011 John Wiley & Sons, Ltd.
Synthesis, Characterizations, and Crystal Structure of a new Cadmium(II) Coordination Polymer Containing Pyrazine Moiety[{Cd(pyz)2(OAc)}n]·n(ClO4)
Authors: Heshmatpour Felora , Morsali Ali , Asadi Jouzani Adel , Neumüller Bernhard
Published: September 2011

Abstract. A new coordination polymer derived from CdII with pyrazine has been synthesized and characterized by elemental analysis, IR,1H, and 13C{1H} NMR spectroscopy and studied by thermal analyses. The structure of [{Cd(pyz)2(OAc)}n]·n(ClO4) (1) was determined byX‐ray diffraction analysis. It crystallizes in the tetragonal system, space group P4/n, with lattice parameters a = 1044.8(1), b = 1044.8(1),c = 652.2(1) pm, Z = 2. The crystal structure consists of monomeric molecules of 1 with distorted octahedral arrangement for theCd(OAc)2N4 chromophore.
Interest Reductions in the Politico-Financial Nexus of Eighteenth-Century England
Authors: Chamley Christophe
Published: September 2011

In the 1730s and 1750s the English government proposed to refinance the redeemable debt by “lowering the interest rate.” In the ensuing coordination game among creditors, large investors like the Bank of England could block the policy change by demanding cash. Using 4 percent and 3 percent annuities prices to analyze market expectations, this article studies two refinancing episodes with very different fates. Lord Barnard failed in 1737 because his terms were too strict and financial agents induced a temporary market crash. Lord Pelham succeeded in 1750 because his better terms fit market prices, and interest rates had fallen much faster than expected.
Feeding ecology of striped dolphins, Stenella coeruleoalba, in the north-western Mediterranean Sea based on stable isotope analyses
Authors: Meissner A.M. , MacLeod C.D. , Richard P. , Ridoux V. , Pierce G.
Published: September 2011

The feeding ecology of striped dolphin, Stenella coeruleoalba, in the north-western Mediterranean Sea was studied using stable isotope analyses. Carbon and nitrogen stable isotope ratios were measured in skin and muscle tissues of stranded and by-caught dolphins from six geographical areas in the Mediterranean Sea and Atlantic Ocean. Variation in δ15N in relation to dolphin size is attributed to changes in diet. Nursing calves have a higher trophic level than weaned animals and their δ15N values decrease progressively until weaning, estimated to be at a body length of around 155 cm. δ15N values then increased for larger individuals which suggests changes in diet for mature dolphins. Geographical differences in diet were apparent between the Atlantic and the Mediterranean, although no clear differences were apparent between the five Mediterranean areas. Comparisons of the nitrogen isotope ratios of skin and muscle highlighted a higher fractionation in skin compared to the muscle tissue. Values of δ13C also increased with body length although it appears that this is not only driven by trophic level enrichment. δ13C increases before weaning and the difference in trophic level between newly-weaned and mature dolphins was twice as high for carbon as for nitrogen. Ontogenetic changes in carbon isotope composition may therefore be driven by feeding on deep water prey and dolphin movements outside the coastal feeding grounds. Indeed, seasonal variations in δ13C are suspected to be driven by migration within the Mediterranean basin.
A Piezoelectric Goniometer Inside a Transmission Electron Microscope Goniometer
Authors: Guan Wei , Lockwood Aiden , Inkson Beverley J. , Möbus Günter
Published: September 2011

Piezoelectric nanoactuators, which can provide extremely stable and reproducible positioning, are rapidly becoming the dominant means for position control in transmission electron microscopy. Here we present a second-generation miniature goniometric nanomanipulation system, which is fully piezo-actuated with ultrafine step size for translation and rotation, programmable, and can be fitted inside a hollowed standard specimen holder for a transmission electron microscope (TEM). The movement range of this miniaturized drive is composed of seven degrees of freedom: three fine translational movements (X,Y, andZaxes), three coarse translational movements along all three axes, and one rotational movement around theX-axis with an integrated angular sensor providing absolute rotation feedback. The new piezoelectric system independently operates as a goniometer inside the TEM goniometer.In situexperiments, such as tomographic tilt without missing wedge and differential tilt between two specimens, are demonstrated.
Half-metallicity and spin-contamination of the electronic ground state of graphene nanoribbons and related systems: An impossible compromise?
Authors: Huzak M. , Deleuze M. S. , Hajgató B.
Published: September 2011

An analysis using the formalism of crystalline orbitals for extended systems with periodicity in one dimension demonstrates that any antiferromagnetic and half-metallic spin-polarization of the edge states in n-acenes, and more generally in zigzag graphene nanoislands and nanoribbons of finite width, would imply a spin contamination ⟨S2⟩ that increases proportionally to system size, in sharp and clear contradiction with the implications of Lieb's theorem for compensated bipartite lattices and the expected value for a singlet (S = 0) electronic ground state. Verifications on naphthalene, larger n-acenes (n = 3–10) and rectangular nanographene islands of increasing size, as well as a comparison using unrestricted Hartree-Fock theory along with basis sets of improving quality against various many-body treatments demonstrate altogether that antiferromagnetism and half-metallicity in extended graphene nanoribbons will be quenched by an exact treatment of electron correlation, at the confines of non-relativistic many-body quantum mechanics. Indeed, for singlet states, symmetry-breakings in spin-densities are necessarily the outcome of a too approximate treatment of static and dynamic electron correlation in single-determinantal approaches, such as unrestricted Hartree-Fock or Density Functional Theory. In this context, such as the size-extensive spin-contamination to which it relates, half-metallicity is thus nothing else than a methodological artefact.
A tunable microcavity
Authors: Barbour Russell J. , Dalgarno Paul A. , Curran Arran , Nowak Kris M. , Baker Howard J. , Hall Denis R. , Stoltz Nick G. , Petroff Pierre M. , Warburton Richard J.
Published: September 2011

We present a generic microcavity platform for cavity experiments on optically active nanostructures, such as quantum dots, nanocrystals, color centers, and carbon nanotubes. The cavity is of the Fabry-Pérot type with a planar back mirror and a miniature concave top mirror with radius of curvature ∼ 100 μm. Optical access is achieved by free beam coupling, allowing good mode-matching to the cavity mode. The cavity has a high Q-factor, reasonably small mode volume, open access, spatial and spectral tunability, and operates at cryogenic temperatures. Spectral and spatial tuning of the Purcell effect (weak coupling regime) on a single InGaAs quantum dot is demonstrated.
Stress-gradient plasticity
Authors: Chakravarthy Srinath S. , Curtin W. A.
Published: September 2011

A new model, stress-gradient plasticity, is presented that provides unique mechanistic insight into size-dependent phenomena in plasticity. This dislocation-based model predicts strengthening of materials when a gradient in stress acts over dislocation source–obstacle configurations. The model has a physical length scale, the spacing of dislocation obstacles, and is validated by several levels of discrete-dislocation simulations. When incorporated into a continuum viscoplastic model, predictions for bending and torsion in polycrystalline metals show excellent agreement with experiments in the initial strengthening and subsequent hardening as a function of both sample-size dependence and grain size, when the operative obstacle spacing is proportional to the grain size.
Megakaryocytes possess a functional intrinsic apoptosis pathway that must be restrained to survive and produce platelets
Authors: Josefsson Emma C. , James Chloé , Henley Katya J. , Debrincat Marlyse A. , Rogers Kelly L. , Dowling Mark R. , White Michael J. , Kruse Elizabeth A. , Lane Rachael M. , Ellis Sarah , Nurden Paquita , Mason Kylie D. , O’Reilly Lorraine A. , Roberts Andrew W. , Metcalf Donald , Huang David C.S. , Kile Benjamin T.
Published: September 2011

It is believed that megakaryocytes undergo a specialized form of apoptosis to shed platelets. Conversely, a range of pathophysiological insults, including chemotherapy, are thought to cause thrombocytopenia by inducing the apoptotic death of megakaryocytes and their progenitors. To resolve this paradox, we generated mice with hematopoietic- or megakaryocyte-specific deletions of the essential mediators of apoptosis, Bak and Bax. We found that platelet production was unperturbed. In stark contrast, deletion of the prosurvival protein Bcl-xL resulted in megakaryocyte apoptosis and a failure of platelet shedding. This could be rescued by deletion of Bak and Bax. We examined the effect on megakaryocytes of three agents that activate the intrinsic apoptosis pathway in other cell types: etoposide, staurosporine, and the BH3 mimetic ABT-737. All three triggered mitochondrial damage, caspase activation, and cell death. Deletion of Bak and Bax rendered megakaryocytes resistant to etoposide and ABT-737. In vivo, mice with a Bak−/− Bax−/− hematopoietic system were protected against thrombocytopenia induced by the chemotherapeutic agent carboplatin. Thus, megakaryocytes do not activate the intrinsic pathway to generate platelets; rather, the opposite is true: they must restrain it to survive and progress safely through proplatelet formation and platelet shedding.
To be, or not to be two sites: that is the question about LeuT substrate binding
Authors: Reyes Nicolas , Tavoulari Sotiria
Published: September 2011

Transport proteins of the neurotransmitter sodium symporter (NSS) family regulate the extracellular concentration of several neurotransmitters in the central nervous system. The only member of this family for which atomic-resolution structural data are available is the prokaryotic homologue LeuT. This protein has been used as a model system to study the molecular mechanism of transport of the NSS family. In this Journal Club, we discuss two strikingly different LeuT transport mechanisms: one involving a single high-affinity substrate binding site and one recently proposed alternative involving two high-affinity substrate binding sites that are allosterically coupled.
Metavir: a web server dedicated to virome analysis
Authors: Roux Simon , Faubladier Michaël , Mahul Antoine , Paulhe Nils , Bernard Aurélien , Debroas Didier , Enault François
Published: September 2011

Summary: Metavir is a web server dedicated to the analysis of viral metagenomes (viromes). In addition to classical approaches for analyzing metagenomes (general sequence characteristics, taxonomic composition), new tools developed specifically for viral sequence analysis make it possible to: (i) explore viral diversity through automatically constructed phylogenies for selected marker genes, (ii) estimate gene richness through rarefaction curves and (iii) perform cross-comparison against other viromes using sequence similarities. Metavir is thus unique as a platform that allows a comprehensive virome analysis.

Availability: Metavir is freely available online at: http://metavir-meb.univ-bpclermont.fr

Contact:  simon.roux@univ-bpclermont.fr

Supplementary Information:  Supplementary data are available at Bioinformatics online.
The growth hormone receptor gene deleted for exon three (GHRd3) polymorphism is associated with birth and placental weight
Authors: Padidela Raja , Bryan Sinead M. , Abu‐Amero Sayeda , Hudson‐Davies Rebecca E. , Achermann John C. , Moore Gudrun E. , Hindmarsh Peter C.
Published: September 2011

Context  Human growth hormone receptor (GHR) transcripts have two isoforms, full‐length (GHRfl) or exon 3 deleted (GHRd3). An association of these isoforms has been found with small for gestational age (SGA) infants but does not influence adult height. The role of this polymorphism in the birth size spectrum in the general population is unclear.

Objective  To determine the association of maternal and infants GHR exon 3 polymorphism with antenatal growth, birth size and early postnatal growth in two large, normal white European birth cohorts.

Study design  Pregnant women from white European families were recruited by the University College London Foetal Growth Study (n = 774) and the Moore normal pregnancy cohort (n = 274). GHR variants, wild‐type (fl) and deleted for exon 3 (d3) were analysed using multiplex PCR.

Results  There was a significant underrepresentation of infants wild‐type fl/fl (36%) and overrepresentation of d3/d3 (14%) genotypes in the SGA infants within the cohorts (χ2 = 11·2, P = 0·003, df = 2). Fl/fl was overrepresented in large for gestational age (LGA) infants (χ2 = 6·1, P = 0·047, df = 2). There was a significant association of infants GHR isoforms with placental weight (P < 0·001) and birth weight standard deviation scores (P = 0·04) with the fl/fl genotype associated with a larger placental and birth weight. In multiple regression analysis, the GHR isoform type, maternal booking weight and parity influenced placental weight (R2 = 0·35; P < 0·001, df = 7). The GHR isoform type was not related to antenatal anthropometric measurements or growth in infancy.

Conclusion  These data suggest that the GHR isoforms are associated with placental and birth weight.
Challenges of rare disease research: limited patients and competing priorities
Authors: RAGNI M. V. , MOORE C. G. , BIAS V. , KEY N. S. , KOUIDES P. A. , FRANCIS C. W. ,   for the Hemostasis Thrombosis Research Society (HTRS)
Published: September 2011

Summary.  Rare disease research is increasingly challenging. For those with haemophilia, this is an exciting time, with the promise of new therapies at the bench and in early phase clinical trials. Yet, it is also a time for critical assessment and planning to assure the success of the clinical research effort. As successes at the bench have enabled transition of novel peptides, longer‐acting factor products and gene therapy to clinical trials, clinicians face the challenges of limited number of patients, competing priorities and strained resources. To solve these problems and assure the success of the clinical research effort, it is essential that the research process be enabling and the dialogue be global, involving academia with industry, and physicians with patients. This is a critical juncture in the process, especially with new national initiatives in clinical research at hand. Needs must be assessed and priorities must be set to assure that despite the challenges, exciting new therapies will ultimately translate into safe, effective therapies for patients. Finally, these challenges are by no means restricted only to rare disease research. With the evolution of genetic medicine, it is likely that the general medical disease research of the future will include small clinical trials of new agents for small subsets of patients with certain disease mutations. Thus, the milestones we achieve in this ongoing process will hopefully not only enable clinical trials research in a rare disease, but also in many medical genetic disease of the future.
Deaths associated with acquired haemophilia in France from 2000 to 2009: multiple cause analysis for best care strategies
Authors: AOUBA A. , REY G. , PAVILLON G. , JOUGLA E. , ROTHSCHILD C. , TORCHET M‐F. , GUILLEVIN L. , HERMINE O. , AOUBA A.
Published: September 2011

Summary.  Deaths occurring in the context of acquired haemophilia (AH) may be related to inter‐connected causes and mechanisms including bleeding, specific or older patient co‐morbidities or iatrogenic complications. However, their magnitude remains unknown. This study aimed to determine the respective weight and frequency of the various causes of death in AH. Multiple‐cause analysis based on death certificates data is used in this purpose. Over a 10‐year period (2000–2009), 121 deaths with AH as a cause were registered in France. All the deaths were of adults (extremes: 47 and 99 years; mean age: 80.7 years). The average number of causes per death certificate was 4.7. AH was the underlying cause of death (UCD) in 69.4% of the cases, and was more frequent in the older subjects. In contrast, before age of 75 years, AH was more often a contributing cause of death. No postpartum or obvious thromboembolism‐related deaths were registered. Haemorrhagic shock was the most frequent direct cause of death (DCD), followed by infectious events, cardiac dysfunction, metabolic and nutritional disorders with muscle wasting and decubitus complications, and cancers (52.9%, 26.4%, 7.5%, 5.8% and 4.1%, respectively). However, when AH was not reported as an UCD, infections become the first DCD (32.4%) followed by bleeding events (16.2%). Best prophylactic and curative strategies for infections are particularly required to improve the prognosis in AH. Moreover, as several of its DCD correspond also to steroids side effects, best tolerated immunosuppressant regimen with steroid‐sparing agents adjoining are particularly awaited in AH population.
Antimalarial efficacy of piperaquine‐based antimalarial combination therapies: facts and uncertainties
Authors: Gargano Nicola , Cenci Fabio , Bassat Quique
Published: September 2011

Piperaquine is a bisquinoline antimalarial drug extensively used as monotherapy in China in the 1980s and subsequently included as one of the components of the artemisinin‐based combination therapies (ACTs) in the 1990s. Among them, dihydroartemisinin–piperaquine (DHA‐PQP) represents a new and extremely promising fixed combination. Several clinical trials have repeatedly shown that DHA‐PQP is a safe and highly efficacious therapy against uncomplicated Plasmodium falciparum and the asexual stages of Plasmodium vivax malaria. Studies conducted with this drug have reported cure rates consistently above 95%, with the only exception being a study carried out in Papua New Guinea which reported a high rate of treatment failures. Although it has been hypothesized that such treatment failures could be related to cross‐resistance mechanisms between piperaquine and other quinolines or to a reduced susceptibility of parasites to artemisinin derivatives, a critical review of the studies published so far seems to exclude both of these possibilities. Overall, there is now sufficient evidence on the safety and efficacy of the DHA‐PQP therapy. Accordingly, the use of this ACT for the treatment of P. falciparum malaria has been recently approved in the EU via a centralized procedure by the European Medicines Agency. Moreover, it is now recommended globally by the World Health Organization as an option for the first‐line treatment of uncomplicated malaria.
The role of recovery of mitochondrial structure and function in desiccation tolerance of pea seeds
Authors: Wang Wei‐Qing , Cheng Hong‐Yan , Møller Ian M. , Song Song‐Quan
Published: September 2011

Mitochondrial repair is of fundamental importance for seed germination. When mature orthodox seeds are imbibed and germinated, they lose their desiccation tolerance in parallel. To gain a better understanding of this process, we studied the recovery of mitochondrial structure and function in pea (Pisum sativum cv. Jizhuang) seeds with different tolerance to desiccation. Mitochondria were isolated and purified from the embryo axes of control and imbibed–dehydrated pea seeds after (re‐)imbibition for various times. Recovery of mitochondrial structure and function occurred both in control and imbibed–dehydrated seed embryo axes, but at different rates and to different maximum levels. The integrity of the outer mitochondrial membrane reached 96% in all treatments. However, only the seeds imbibed for 12 h and then dehydrated recovered the integrity of the inner mitochondrial membrane (IMM) and State 3 (respiratory state in which substrate and ADP are present) respiration (with NADH and succinate as substrate) to the control level after re‐imbibition. With increasing imbibition time, the degree to which each parameter recovered decreased in parallel with the decrease in desiccation tolerance. The tolerance of imbibed seeds to desiccation increased and decreased when imbibed in CaCl2 and methylviologen solution, respectively, and the recovery of the IMM integrity similarly improved and weakened in these two treatments, respectively. Survival of seeds after imbibition–dehydration linearly increased with the increase in ability to recover the integrity of IMM and State 3 respiration, which indicates that recovery of mitochondrial structure and function during germination has an important role in seed desiccation tolerance.
Aloe vera extract reduces both growth and germ tube formation by Candida albicans
Authors: Bernardes Ivy , Felipe Rodrigues Monalisa Poliana , Bacelli Gabrielle Klug , Munin Egberto , Alves Leandro Procópio , Costa Maricilia Silva
Published: September 2011

Due to the increased number of immunocompromised patients, the infections associated with the pathogen of the genus Candida have significantly increased in recent years. To grow, Candida albicans may form a germ tube extension from the cells, which is essential for virulence. In this work, we studied the effect of crude glycolic extract of Aloe vera fresh leaves (20% w/v) on growth and germ tube formation by C. albicans. The C. albicans growth was determined in the presence of different concentrations of A. vera extracts in Sabouraud dextrose broth medium. In the presence of A. vera extract (10% v/v), the pronounced inhibition in the C. albicans growth (90–100%) was observed. This inhibition occurred parallel to the decrease in the germ tube formation induced by goat serum. Our results demonstrated that A. vera fresh leaves plant extract can inhibit both the growth and the germ tube formation by C. albicans. Our results suggest the possibility that A. vera extract may be used as a promising novel antifungal treatment.
Gestational diabetes mellitus in five ethnic groups: a comparison of their clinical characteristics
Authors: Wong V. W.
Published: September 2011

Diabet. Med. 29, 366–371 (2012)

Aims  The prevalence of gestational diabetes mellitus has been shown to vary between ethnic groups. The differences in the clinical characteristics and outcomes of women with gestational diabetes mellitus from various ethnic groups have not been clearly defined.

Methods  A retrospective review of women with gestational diabetes mellitus from a single institution between 2007 and 2010 was conducted. The clinical profiles of women from five ethnic groups (South‐East Asian, South Asian, Middle Eastern, Anglo‐European and Pacific Islander) were documented, including the outcomes of their pregnancy.

Results  In this cohort of 827 women from these five ethnic groups, South‐East Asians had the lowest BMI, lowest fasting (yet highest 2‐h) glucose level on 75‐g glucose tolerance test, lowest need for insulin therapy and lowest rate of macrosomia. South Asians had the lowest parity but strongest family history of diabetes. Their offspring also had the lowest birthweight. Women from Pacific Islands had the highest parity, BMI, fasting glucose levels on 75‐g glucose tolerance test, HbA1c (at diagnosis of gestational diabetes mellitus as well as at 36 weeks’ gestation) and greatest need for insulin therapy. Their offspring also had the highest birthweights.

Conclusion  This study highlighted the significant differences in clinical characteristics of women with gestational diabetes mellitus among five ethnic groups. These differences may need to be considered in the management of gestational diabetes mellitus, especially in the interpretation of normality for pregnancy.
Intensive multifactorial intervention improves modelled coronary heart disease risk in screen‐detected Type 2 diabetes mellitus: a cluster randomized controlled trial
Authors: Webb D. R. , Khunti K. , Gray L. J. , Srinivasan B. T. , Farooqi A. , Wareham N. , Griffin S. C. , Davies M. J. ,   for the ADDITION‐Leicester study group
Published: September 2011

Diabet. Med. 29, 531–540 (2012)

Aims  To compare the effects of intensive multifactorial cardiovascular risk intervention with standard care in screen‐detected Type 2 diabetes.

Methods  Twenty general practices randomly invited 30 950 adults without diagnosed diabetes for screening (World Health Organization, 1999). In a cluster randomized controlled trial, screen‐detected cases were assigned by practice allocation to receive intensive protocol‐driven cardiovascular risk management (n = 146) or standard care (n = 199) according to local guidelines. Intensive intervention was designed to achieve an HbA1c of 48 mmol/mol (6.5%), blood pressure < 130/80 mmHg and total cholesterol < 3.5 mmol/l. Primary outcome was modelled 5‐year coronary heart disease risk (UKPDS‐CHD). Analysis was via intention to treat.

Results  After 1.1 years 339 (98%) individuals were still participating. There were significant reductions in HbA1c, blood pressure and total cholesterol from baseline in both groups [mean change for total study population −27.7 mmol/mol (−0.62%), −11.64/10.01 mmHg, −1.11 mmol/l]. After adjustment for baseline and clustering, significant inter‐group differences were observed in mean changes from baseline for HbA1c{−28.5 mmol/mol [−0.7% (1.4)] vs. −27.5 mmol/mol [−0.6% (1.6)], P = 0.001}, blood pressure [systolic −16.2 (19.6) vs. −8.4 (18.6) mmHg, P < 0.001], total cholesterol [−1.3 (1.3) vs. −1.0 (1.2) mmol/l, P < 0.001] and weight [−3.8 (5.5) vs. −2.2 (5.5) kg, P = 0.01] in favour of intensive treatment. UKPDS 5‐year coronary heart disease risk was reduced by 3.2% and 2.3%, respectively (P < 0.0001). Intensive intervention was associated with more lipid‐lowering and anti‐hypertensive but not hypoglycaemic medication use [odds ratios 2.5 (1.4–4.4), 5.5 (2.4–11.5), 1.6 (0.8–2.3); compared with standard care, P < 0.001, P = 0.003, P = 0.65]. Treatment satisfaction responses were superior with intensive intervention, with no increase in self‐reported hypoglycaemia.

Conclusion  Intensive intervention in patients with diabetes identified through systematic non‐risk‐factor‐based screening significantly reduces modelled coronary heart disease risk. This is achieved predominantly with lipid‐lowering and anti‐hypertensive treatments with no adverse effect on quality of life or hypoglycaemia.