bluuebunny/crossref_metadata_2025 huggingface dataset:
miR-21 as a key regulator of oncogenic processes
Authors: Selcuklu S. Duygu , Donoghue Mark T.A. , Spillane Charles
Published: July 2009

Small non-coding miRNAs (microRNAs) are emerging as key factors involved in cancer at all stages ranging from initiation to metastasis. MIRN21 is an miRNA gene that codes for the miR-21 miRNA which has been found to be overexpressed in many tumour samples where it has been analysed. Whereas consistent overexpression of miR-21 in tumours could be suggestive of functional effects of miR-21 in cancer, more in-depth functional studies with miR-21 are demonstrating that mir-21 displays oncogenic activity and can be classed as an oncomir. Extensive efforts are underway to identify the downstream genes and gene networks regulated by miR-21 and to identify the upstream factors that are regulating expression of miR-21. Even though miR-21 is one of the most intensively studied miRNAs, for all miRNAs, our understanding of miRNA signalling pathways is currently in its early stages. The unravelling of such RNA signalling pathways and networks will be key to understanding the role that dysregulated miRNA functioning can play in oncogenic processes.
Pulse shaping and energy storage capabilities of angularly multiplexed KrF laser fusion drivers
Authors: Lehmberg R. H. , Giuliani J. L. , Schmitt A. J.
Published: July 2009

This paper describes a rep-rated multibeam KrF laser driver design for the 500kJ Inertial Fusion test Facility (FTF) recently proposed by NRL, then models its optical pulse shaping capabilities using the ORESTES laser kinetics code. It describes a stable and reliable iteration technique for calculating the required precompensated input pulse shape that will achieve the desired output shape, even when the amplifiers are heavily saturated. It also describes how this precompensation technique could be experimentally implemented in real time on a reprated laser system. The simulations show that this multibeam system can achieve a high fidelity pulse shaping capability, even for a high gain shock ignition pulse whose final spike requires output intensities much higher than the ∼4MW∕cm2 saturation levels associated with quasi-cw operation; i.e., they show that KrF can act as a storage medium even for pulsewidths of ∼1ns. For the chosen pulse, which gives a predicted fusion energy gain of ∼120, the simulations predict the FTF can deliver a total on-target energy of 428kJ, a peak spike power of 385TW, and amplified spontaneous emission prepulse contrast ratios IASE∕I<3×10−7 in intensity and FASE∕F<1.5×10−5 in fluence. Finally, the paper proposes a front-end pulse shaping technique that combines an optical Kerr gate with cw 248nm light and a 1μm control beam shaped by advanced fiber optic technology, such as the one used in the National Ignition Facility (NIF) laser.
How to tell when a model Kohn–Sham potential is not a functional derivative
Authors: Gaiduk Alex P. , Staroverov Viktor N.
Published: July 2009

A model exchange-correlation potential constructed with Kohn–Sham orbitals should be a functional derivative of some density functional. Several necessary conditions for a functional derivative are discussed including: (i) minimization of the total-energy expression by the ground-state solution of the Kohn–Sham equations, (ii) path independence of the van Leeuwen–Baerends line integral, and (iii) net zero force and zero torque on the density. A number of existing model potentials are checked for these properties and it is found that most of the potentials tested are not functional derivatives. Physical properties obtained from potentials that have no parent functionals are ambiguous and, therefore, should be interpreted with caution.
Monte Carlo study of device characteristics of GaN-based avalanche photodiode devices
Authors: Zheng Zhiyuan , Mai Yuxiang , Wang Gang
Published: July 2009

In this article, Monte Carlo method is used to study the characteristics of gallium nitride (GaN). Impact ionization is treated as an additional scattering mechanism, which is described by the Keldysh formula with the parameters determined by fitting the simulated results to the numerical calculation results. Based on simplified model, results of velocity overshoot and impact ionization rate of both carriers are calculated and analyzed. In addition, we get the device characteristics associated with impact ionization, i.e., gain, noise, and bandwidth (both electron- and hole-injected cases), which is compared to the reported experimental data and conventional theories. Moreover, we contrast the simulated device characteristics of GaN and the performance of several conventional materials.
Surface plasmon isolator based on nonreciprocal coupling
Authors: Montoya Juan , Parameswaran Krishnan , Hensley Joel , Allen Mark , Ram Rajeev
Published: July 2009

Integrated photonics require optical isolators that achieve low insertion loss and large optical isolation. Here we describe a surface plasmon enhanced optical isolator based on nonreciprocal coupling from a dielectric waveguide coupled to a surface plasmon waveguide. The surface plasmon core consists of a magnetic metal which results in a large nonreciprocity, allowing for device lengths on the order of 50 μm. The analysis and modeling presented here indicate that greater than 30 dB isolation and less than 3 dB insertion loss are possible.
Dielectric studies of Co3−xMnxO4 (x=0.1–1.0) cubic spinel multiferroic
Authors: Meena P. L. , Kumar Ravi , Prajapat C. L. , Sreenivas K , Gupta Vinay
Published: July 2009

A series of Co3−xMnxO4 (x=0.1–1.0) multiferroic cubic spinel ceramics were prepared to study the effect of Mn substitution at Co site on the crystal structures and dielectric properties. No significant change in the structural symmetry was observed with increasing x up to 1.0. A linear increase in lattice parameter with x is attributed to the substitution of Co3+ by Mn3+ (large ionic radii) at the octahedral sites. An antiferromagnetic-type ordering of Co3O4 changes to ferrimagnetic-type order after incorporation of Mn. The effect of Mn substitution on the dielectric constant and loss tangent was studied over a wide range of frequency (75 kHz–5 MHz) and temperature of 150–450 K. The measured value of room temperature ac conductivity at 1.0 MHz was found to increase from 2.0×10−6 to 4.4×10−4 Ω−1 cm−1 and follows power law (σac=Aωs) behavior. The dielectric constant ε′(ω) shows a weak frequency dispersion and small temperature dependence below 250 K for all ceramic samples. However, a strong temperature and frequency dependence on ε′(ω) was observed at higher temperature (>250 K). The temperature dependent ε′(ω) data show the existence of room temperature ferroelectricity in all prepared samples.
A simple lattice model for the microstructure of neat alcohols: Application to liquid methanol
Authors: Ciach Alina , Perera Aurélien
Published: July 2009

Simple lattice model for self-associating molecules such as methanol or tert-butanol is proposed and studied in mean-field (MF) approximation in the case of methanol. In addition to the isotropic van der Waals interaction, the hydrogen bonding is present in this model when the neighboring alcohol molecules are in appropriate orientations. The orientation of the polar molecule is given by the unit vector n̂ parallel to the vector connecting the center of the tail group with the center of the head group of the molecule. Stability region of the uniform fluid phase against gas-liquid separation and order-disorder transition is obtained for neat methanol in MF approximation. In order to describe the self-association patterns in the liquid, we consider the grand-canonical ensemble average of the scalar product of the orientations of the molecules ⟨n̂(x)⋅n̂(x+Δx)⟩ as a function of the vector Δx describing the separation between the centers of the molecules. For methanol we find in MF oscillatory decay of ⟨n̂(x)⋅n̂(x+Δx)⟩ for Δx⊥n̂(x) and for Δx∥n̂(x); the wavelength is somewhat less than two molecular diameters in both cases, and the decay length is larger in the perpendicular direction. This indicates that on average alternating antiparallel and parallel orientations of the second molecule are found for increasing separation from the first molecule in both directions. Such local orientational ordering of the molecules is consistent with association into zigzag chainlike clusters found in recent spectroscopic measurements and computer simulations. In Fourier representation the above structure function assumes maximum for the wave number that coincides with the prepeak position for site-site correlations found in simulations. We argue that ⟨n̂(x)⋅n̂(x+Δx)⟩ can provide a useful tool for discriminating between different local arrangements of any polar molecules.
Top-emission Si-based phosphor organic light emitting diode with Au doped ultrathin n-Si film anode and bottom Al mirror
Authors: Li Y. Z. , Xu W. J. , Ran G. Z. , Qin G. G.
Published: July 2009

We report a highly efficient top-emission Si-based phosphor organic light emitting diode (PhOLED) with an ultrathin polycrystalline n-Si:Au film anode and a bottom Al mirror. This anode is formed by magnetron sputtering followed by Ni induced crystallization and then Au diffusion. By optimizing the thickness of the n-Si:Au film anode, the Au diffusion temperature, and the other parameters of the PhOLED, the highest current and power efficiencies of the n-Si:Au film anode PhOLED reached 85±9 cd/A and 80±8 lm/W, respectively, corresponding to an external quantum efficiency of 21±2% and a power conversion efficiency of 15±2%, respectively, which are about 60% and 110% higher than those of the indium tin oxide anode counterpart and 70% and 50% higher than those of the bulk n+-Si:Au anode counterpart, respectively.
Proton transfer and H/D isotopic exchange of water molecules mediated by hydroxide ions on ice film surfaces
Authors: Kim Jung-Hwan , Kim Young-Kwang , Kang Heon
Published: July 2009

The effect of hydroxide ions on proton transfer and H/D isotopic exchange of water molecules was examined at the surface of amorphous ice films at temperatures of 92–140 K. Excess hydroxide ions were provided onto a D2O-ice film by the hydrolysis of Na atoms, and H2O was adsorbed onto the surface for a submonolayer coverage. The H/D isotopic exchange between H2O and D2O molecules on the ice film surface was monitored as a function of reaction time and temperature by using the techniques of reactive ion scattering and low-energy sputtering. The result was compared with that obtained on a hydroxide-free ice film. At a temperature of 92 K, proton transfer occurred from water mostly to adjacent hydroxide ions. The proton transfer distance and the H/D exchange reaction rate increased with increase in temperature above 105 K. The H/D exchange reaction propagated to several water molecules on the surface at 100–120 K. Kinetic measurement in this temperature range deduced the Arrhenius activation energy for the reaction, Ea=9.6±2.0 kJ mol−1. The study shows that hydroxide ions promote the H/D exchange reaction on the ice surface compared with that on a hydroxide-free ice surface, but the promotion effect is moderate and the H/D exchange occurs on a substantial energy barrier. It is suggested that the stabilization of hydroxide ions at the ice surface produces an energy barrier for the proton transfer.
Kalirin regulates cortical spine morphogenesis and disease-related behavioral phenotypes
Authors: Cahill Michael E. , Xie Zhong , Day Michelle , Photowala Huzefa , Barbolina Maria V. , Miller Courtney A. , Weiss Craig , Radulovic Jelena , Sweatt J. David , Disterhoft John F. , Surmeier D. James , Penzes Peter
Published: July 2009

Dendritic spine morphogenesis contributes to brain function, cognition, and behavior, and is altered in psychiatric disorders. Kalirin is a brain-specific guanine-nucleotide exchange factor (GEF) for Rac-like GTPases and is a key regulator of spine morphogenesis. Here, we show that
KALRN
-knockout mice have specific reductions in cortical, but not hippocampal, Rac1 signaling and spine density, and exhibit reduced cortical glutamatergic transmission. These mice exhibit robust deficits in working memory, sociability, and prepulse inhibition, paralleled by locomotor hyperactivity reversible by clozapine in a kalirin-dependent manner. Several of these deficits are delayed and age-dependent. Our study thus links spine morphogenic signaling with age-dependent, delayed, disease-related phenotypes, including cognitive dysfunction.
Neurocognitive Function in Attention-Deficit–Hyperactivity Disorder with and Without Comorbid Disruptive Behaviour Disorders
Authors: Barnett Rebecca , Maruff Paul , Vance Alasdair
Published: July 2009

Objective: The aim of the present study was to examine the effect of comorbid oppositional defiant disorder (ODD) and conduct disorder (CD) on (i) symptom levels in attention-deficit–hyperactivity disorder (ADHD) and (ii) the relationship between neurocognitive impairment and ADHD symptom severity.

Method: A total of 200 6–12-year-old children with DSM-IV ADHD, combined type (ADHD-CT) were identified in a specialist ADHD clinic in metropolitan Melbourne. From this initial group, 23 were identified with ADHD without ODD/CD (ADHD alone), 22 had ADHD and ODD and 20 had ADHD and CD. All the children were medication naïve. Twenty-five healthy control children were also recruited from local primary schools. The four groups did not differ in age, gender or full-scale IQ. A cross-sectional study of parent- and teacher-reported ADHD and externalizing symptoms, spatial span, spatial working memory, visuospatial memory, spatial recognition, spatial planning and behavioural inhibition was completed.

Results: Parent-reported externalizing symptoms were higher in the ADHD + CD and ADHD + ODD groups compared to the ADHD alone group. There were no differences in neurocognitive function between children with ADHD-CT with and without ODD or CD. All the ADHD groups, however, performed worse than the healthy control group. Further, worse spatial span, spatial working memory and delayed matching to sample performance were associated with increased teacher-reported ADHD symptoms in the ADHD alone group. Also, worse spatial working memory performance was associated with increased teacher-reported ADHD symptoms in the ADHD + CD group.

Conclusions: ADHD symptom severity is associated with the magnitude of impairment in executive functions in children with ADHD alone, but these relationships can be obscured by the presence of comorbid disruptive disorders. Children with ADHD + CD may demonstrate similar associations to children with ADHD alone, suggesting a similar underlying dysfunction. ADHD + ODD, however, may be better understood as a maladaptive response to the abnormal behaviours and neurocognitive functions in ADHD.
Quality of Life in Parents of Children with Attention-Deficit–Hyperactivity Disorder in Hong Kong
Authors: Xiang Yu-Tao , Luk Ernest S. L. , Lai Kelly Y. C.
Published: July 2009

Objective: There is no study on the quality of life (QOL) of parents of children with attention-deficit–hyperactivity disorder (ADHD), although QOL is increasingly gaining more attention and the interactions between children and their parents are bi-directional. The aim of the present study was therefore to survey the QOL of parents of children with ADHD in Hong Kong, and explore the relationships of sociodemographic and clinical variables with QOL.

Method: Seventy-seven parents of children with ADHD were consecutively selected and the sociodemographic and clinical characteristics of the parents and their children were assessed.

Results: Compared with the general population in Hong Kong, significantly lower scores in physical, psychological, social and environmental QOL domains were found in the parents of children with ADHD. On multivariate analysis, for the children with ADHD, the severity of emotional and hyperactivity/inattention symptoms, and having a comorbid pervasive developmental disorder were significantly correlated with one or more domains of QOL; while for the parents, educational level, household monthly income and having major medical conditions were significantly correlated with one or more domains of QOL.

Conclusions: Parents of children with ADHD have low QOL and research is needed to understand the underlying problems.
Infant Discrimination of a Morphologically Relevant Word‐Final Contrast
Authors: Fais Laurel , Kajikawa Sachiyo , Amano Shigeaki , Werker Janet F.
Published: July 2009

Six‐, 12‐, and 18‐month‐old English‐hearing infants were tested on their ability to discriminate nonword forms ending in the final stop consonants /k/ and /t/ from their counterparts with final /s/ added, resulting in final clusters /ks/ and /ts/, in a habituation–dishabituation, looking time paradigm. Infants at all 3 ages demonstrated an ability to discriminate this type of contrast, a contrast that constitutes one phonetic cue for the English morphological concepts of plural, possession, and person. These results suggest that across a significant portion of the development of infants' speech perception, this type of final contrast is discriminable.
Phosphorylation of Zona Occludens-2 by Protein Kinase Cε Regulates Its Nuclear Exportation
Authors: Chamorro David , Alarcón Lourdes , Ponce Arturo , Tapia Rocio , González-Aguilar Héctor , Robles-Flores Martha , Mejía-Castillo Teresa , Segovia José , Bandala Yamir , Juaristi Eusebio , González-Mariscal Lorenza
Published: July 2009

Here, we have analyzed the subcellular destiny of newly synthesized tight junction protein zona occludens (ZO)-2. After transfection in sparse cells, 74% of cells exhibit ZO-2 at the nucleus, and after 18 h the value decreases to 17%. The mutation S369A located within the nuclear exportation signal 1 of ZO-2 impairs the nuclear export of the protein. Because Ser369 represents a putative protein kinase C (PKC) phosphorylation site, we tested the effect of PKC inhibition and stimulation on the nuclear export of ZO-2. Our results strongly suggest that the departure of ZO-2 from the nucleus is regulated by phosphorylation at Ser369 by novel PKCε. To test the route taken by ZO-2 from synthesis to the plasma membrane, we devised a novel nuclear microinjection assay in which the nucleus served as a reservoir for anti-ZO-2 antibody. Through this assay, we demonstrate that a significant amount of newly synthesized ZO-2 goes into the nucleus and is later relocated to the plasma membrane. These results constitute novel information for understanding the mechanisms that regulate the intracellular fate of ZO-2.
Path: a tool to facilitate pathway-based genetic association analysis
Authors: Zamar David , Tripp Ben , Ellis George , Daley Denise
Published: July 2009

Summary: Traditional methods of genetic study design and analysis work well under the scenario that a handful of single nucleotide polymorphisms (SNPs) independently contribute to the risk of disease. For complex diseases, susceptibility may be determined not by a single SNP, but rather a complex interplay between SNPs. For large studies involving hundreds of thousands of SNPs, a brute force search of all possible combinations of SNPs associated with disease is not only inefficient, but also results in a multiple testing paradigm, whereby larger and larger sample sizes are needed to maintain statistical power. Pathway-based methods are an example of one of the many approaches in identifying a subset of SNPs to test for interaction. To help determine which SNP–SNP interactions to test, we developed Path, a software application designed to help researchers interface their data with biological information from several bioinformatics resources. To this end, our application brings together currently available information from nine online bioinformatics resources including the National Center for Biotechnology Information (NCBI), Online Mendelian Inheritance in Man (OMIM), Kyoto Encyclopedia of Genes and Genomes (KEGG), UCSC Genome Browser, Seattle SNPs, PharmGKB, Genetic Association Database, the Single Nucleotide Polymorphism database (dbSNP) and the Innate Immune Database (IIDB).

Availability: The software, example datasets and tutorials are freely available from http://genapha.icapture.ubc.ca/PathTutorial.

Contact:  ddaley@mrl.ubc.ca
Design of the Reduction of Events with Darbepoetin alfa in Heart Failure (RED‐HF): a Phase III, anaemia correction, morbidity–mortality trial
Authors: McMurray John J.V. , Anand Inder S. , Diaz Rafael , Maggioni Aldo P. , O'Connor Christopher , Pfeffer Marc A. , Polu Krishna R. , Solomon Scott D. , Sun Yan , Swedberg Karl , Tendera Michal , van Veldhuisen Dirk J. , Wasserman Scott M. , Young James B. ,   on behalf of the RED‐HF Committees and Investigators
Published: July 2009

Background

Patients with heart failure (HF) and anaemia have greater functional impairment, worse symptoms, increased rates of hospital admission, and a higher risk of death, compared with non‐anaemic HF patients. Whether correcting anaemia can improve outcomes is unknown.

Objective

The Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED‐HF; Clinical Trials.gov NCT 003 58215) was designed to evaluate the effect of the long‐acting erythropoietin‐stimulating agent darbepoetin alfa on mortality and morbidity (and quality of life) in patients with HF and anaemia.

Methods

Approximately 2600 patients with New York Heart Association class II–IV, an ejection fraction ≤40%, and a haemoglobin (Hb) consistently ≤12.0 g/dL but ≥9.0 g/dL will be enrolled. Patients are randomized 1:1 to double‐blind subcutaneous administration of darbepoetin alfa or placebo. Investigators are also blinded to Hb measurements and darbepoetin alfa is dosed to achieve an Hb concentration of 13.0 g/dL (but not exceeding 14.5 g/dL) with sham adjustments of the dose of placebo. The primary endpoint is the time to death from any cause or first hospital admission for worsening HF, whichever occurs first. The study will complete when ~1150 subjects experience a primary endpoint.
Sexual selection against deleterious mutations via variable male search success
Authors: MacLellan Kelsie , Whitlock Michael C. , Rundle Howard D.
Published: July 2009

In many species, successful mating requires the initial step of actively searching for and locating a female. The overall health or condition of a male is likely to affect their ability to do this, making search effort a potentially important component of sexual fitness that may have important consequences for population mean fitness. We investigated the potential population genetic consequences of search effort using 10 populations of
Drosophila melanogaster
, each fixed for a different recessive mutation with a visible phenotypic effect. Mate choice trials were conducted in arenas of varying size, requiring different levels of search ability. Sexual selection against mutant males was stronger when increased search effort was included than when it was excluded. Varying abilities to find mates can substantially increase the strength of selection against deleterious alleles.
Unraveling yields inefficient matchings: evidence from post‐season college football bowls
Authors: Fréchette Guillaume R. , Roth Alvin E. , Ünver M. Utku
Published: July 2009

Many markets have “unraveled” and experienced inefficient, early, dispersed transactions, and subsequently developed institutions to delay transaction timing. It has previously proved difficult, however, to measure and identify the resulting efficiency gains. Prior to 1992, college football teams were matched for post‐season play up to several weeks before the end of the regular season. Since 1992, the market has reorganized to postpone this matching. We show that the matching of teams affects efficiency as measured by the resulting television viewership, and that the reorganization promoted more efficient matching, chiefly as a result of the increased ability of later matching to produce “championship” games.
Bidding to lose? Auctions with resale
Authors: Pagnozzi Marco
Published: July 2009

A losing bidder can still purchase the prize from the winner after the auction. We show why a strong bidder may prefer to drop out of the auction before the price has reached her valuation and acquire the prize in the aftermarket: a strong bidder may be in a better bargaining position in the aftermarket if her rival won at a relatively low price. So it can be common knowledge that, in equilibrium, a weak bidder will win the auction and, even without uncertainty about relative valuations, resale will take place. The possibility of reselling to a strong bidder attracts weak bidders to participate in the auction and raises the seller's revenue.
Loss of shoaling preference for familiar individuals in captive‐reared crimson spotted rainbowfish Melanotaenia duboulayi
Authors: Kydd E. , Brown C.
Published: July 2009

Captive‐reared rainbowfish Melanotonia duboulayi showed no preference for familiar individuals in an experiment examining shoaling preferences. Fortnightly re‐examination of the shoaling preferences of the captive‐reared population showed that the lack of preference for familiar individuals did not alter over an 8 week period. The same experiment performed on laboratory‐reared offspring raised in isolated groups for 8 months since hatching also showed no preference for shoals consisting of familiar individuals. In contrast, trials performed on a wild population of M. duboulayi found a strong preference for familiar shoalmates, a result that is consistent with previous studies. The lack of shoaling preferences in captive‐reared populations is probably the result of relaxed selection and inbreeding in the captive environment. The consequences of captive breeding for fish social behaviour are discussed with particular reference to hatchery production.
Effects of the swimbladder parasite Anguillicola crassus on the migration of European silver eels Anguilla anguilla in the Baltic Sea
Authors: Sjöberg N. B. , Petersson E. , Wickström H. , Hansson S.
Published: July 2009

In a mark–recapture study in 2006, migrating European Anguilla anguilla silver eels were caught, tagged and released in the Baltic Sea and recaptures in commercial pound nets examined for possible effects on migration of infection with the swimbladder parasite Anguillicola crassus. The overall recapture rate was 36%. The prevalence of infection was lowest at the northernmost sampling site. There were no significant differences between infected and uninfected A. anguilla in condition indices, body fat content and estimated migration speeds. Parasite infection intensity levels were significantly negatively correlated with times and distances covered between release and recapture, but did not correlate with migration speed. It appears that more heavily infected A. anguilla were relatively more vulnerable to recapture in pound nets. It is hypothesized that parasite‐induced damage to the swimbladder inhibited vertical migrations and infected A. anguilla tended to migrate in shallower coastal waters, relatively close to the shore.
Modelling the impact of an influenza A/H1N1 pandemic on critical care demand from early pathogenicity data: the case for sentinel reporting
Authors: Ercole A. , Taylor B. L. , Rhodes A. , Menon D. K.
Published: July 2009

Projected critical care demand for pandemic influenza H1N1 in England was estimated in this study. The effect of varying hospital admission rates under statistical uncertainty was examined. Early in a pandemic, uncertainty in epidemiological parameters leads to a wide range of credible scenarios, with projected demand ranging from insignificant to overwhelming. However, even small changes to input assumptions make the major incident scenario increasingly likely. Before any cases are admitted to hospital, 95% confidence limit on admission rates led to a range in predicted peak critical care bed occupancy of between 0% and 37% of total critical care bed capacity, half of these cases requiring ventilatory support. For hospital admission rates above 0.25%, critical care bed availability would be exceeded. Further, only 10% of critical care beds in England are in specialist paediatric units, but best estimates suggest that 30% of patients requiring critical care will be children. Paediatric intensive care facilities are likely to be quickly exhausted and suggest that older children should be managed in adult critical care units to allow resource optimisation. Crucially this study highlights the need for sentinel reporting and real‐time modelling to guide rational decision making.
The use of growth hormone (GH)‐dependent markers in the detection of GH abuse in sport: Physiological intra‐individual variation of IGF‐I, type 3 pro‐collagen (P‐III‐P) and the GH‐2000 detection score
Authors: Erotokritou‐Mulligan Ioulietta , Eryl Bassett E. , Cowan David A. , Bartlett Christiaan , Milward Polly , Sartorio Alessandro , Sönksen Peter H. , Holt Richard I. G.
Published: July 2009

Background  Growth Hormone is abused by athletes for its lipolytic and anabolic properties. Its use is prohibited by the World Anti‐Doping Agency. The GH‐2000 project developed a methodology to detect its abuse using the concentrations of two GH‐dependent biomarkers, IGF‐I and type 3 procollagen (P‐III‐P). The sensitivity of this method may be improved by considering intra‐individual variability.

Aim  The aim of this study was to examine the intra‐individual variability of IGF‐I, P‐III‐P and the GH‐2000 score.

Subjects and methods  IGF‐I, P‐III‐P and GH‐2000 score were evaluated in four longitudinal studies involving 303 elite and 78 amateur athletes. Samples were collected over a period of up to 12 months from a total of 238 men and 143 women aged between 17 and 53 years (mean 24·2).

Results  The four studies showed good agreement with no apparent difference in within‐individual variation between amateur and elite athletes. The intra‐individual variability for IGF‐I ranged between 14–16% while the variability for P‐III‐P was 7–18%. No athlete tested positive for growth hormone during any of the studies. The overall mean intra‐individual variability of the GH‐2000 score was less than 0·6 units in all studies.

Conclusions  The high stability of marker levels suggests that concentrations are largely genetically determined. Adopting a test based on the concept of an athlete’s ‘passport’ or ‘profiling’ would take advantage of this and most likely increase the sensitivity of the test. These data also provide strong evidence that a positive test result for GH abuse would not occur as a result of chance variability.
Explicit versus implicit review to explore combination antipsychotic prescribing
Authors: Wheeler Amanda
Published: July 2009

Objective  To use structured implicit review following large‐scale explicit audit of antipsychotic polyprescribing to: (1) determine the true rate of antipsychotic polytherapy that deviated from best practice for schizophrenia treatment; and (2) assess whether explicit antipsychotic polytherapy criterion was appropriate for identifying patients at risk for medication problems and assessing quality of care.

Methods  Antipsychotic prescribing was reviewed for outpatients in four public health services in Auckland, New Zealand on 31 October 2004 (T1). Schizophrenia patients in one service (n = 794) prescribed antipsychotic polytherapy (n = 84, 10.6%) were followed up 10 months later (T2). Historical medication summaries were prepared for those remaining on polytherapy, including diagnosis, clinical problems and treatment plan. Criteria for structured implicit review and rating form for quality of antipsychotic management were piloted. All medication summaries were independently rated by two reviewers, and a third independent rater reviewed summaries where disagreement was found.

Results  Forty‐nine patients remained on long‐term polytherapy at T2 (6.2% of original population). All but two cases included a second‐generation antipsychotic. At T2, average polytherapy duration was 35.8 months, and average antipsychotic dose was 699 mg day−1 chlorpromazine equivalents. Two raters achieved agreement for 24/49 summaries, and the remaining 25 were rated independently by a third reviewer. Consensus agreement of antipsychotic management (by two raters) was reached for 44/49 cases (89.8%). Polytherapy was rated ‘well‐justified’ in 32.7%, ‘some justification’ in 10.2% and ‘lacked justification’ in 46.9% cases. The final rate of polytherapy deviating from best practice reduced from 10.6% to 3.5% when short‐term polytherapy was excluded, and details of the clinical situation and care plan were included in implicit review.

Conclusions  Audit of prescribing in routine practice using explicit guideline‐based criteria may be a useful baseline performance indicator. It does not provide an accurate measurement of quality of care because it overestimates the deviation rate from good practice. It may also identify complex patients at risk for poor treatment outcomes who may benefit from structured treatment review.
3D boundary extraction of confocal cellular images using higher order statistics
Authors: INDHUMATHI C. , CAI Y.Y. , GUAN Y.Q. , OPAS M.
Published: July 2009

In recent years, cell biologists have benefited greatly from using confocal microscopy to study intracellular organelles. For high‐level image analysis, 3D boundary extraction of cell structure is a preliminary requisite in confocal cellular imaging. To detect the object boundaries, most investigators have used gradient/Laplacian operator as a principal tool. In this paper we propose a higher order statistics (HOS) based boundary extraction algorithm for confocal cellular image data set using kurtosis. After the initial pre‐processing, kurtosis boundary map is estimated locally for the entire volume using a cubic sliding window and subsequently the noisy kurtosis value is removed by thresholding. Voxels having positive kurtosis value with zero‐crossing on its surface are then identified as boundary voxels. Typically used in signal processing, kurtosis for 3D cellular image processing is a novel application of HOS. Its reliable and robust nature of computing makes it very suitable for volumetric cellular boundary extraction.
Image analysis for denoising full‐field frequency‐domain fluorescence lifetime images
Authors: SPRING B.Q. , CLEGG R.M.
Published: July 2009

Video‐rate fluorescence lifetime‐resolved imaging microscopy (FLIM) is a quantitative imaging technique for measuring dynamic processes in biological specimens. FLIM offers valuable information in addition to simple fluorescence intensity imaging; for instance, the fluorescence lifetime is sensitive to the microenvironment of the fluorophore allowing reliable differentiation between concentration differences and dynamic quenching. Homodyne FLIM is a full‐field frequency‐domain technique for imaging fluorescence lifetimes at every pixel of a fluorescence image simultaneously. If a single modulation frequency is used, video‐rate image acquisition is possible. Homodyne FLIM uses a gain‐modulated image intensified charge‐coupled device (ICCD) detector, which unfortunately is a major contribution to the noise of the measurement. Here we introduce image analysis for denoising homodyne FLIM data. The denoising routine is fast, improves the extraction of the fluorescence lifetime value(s) and increases the sensitivity and fluorescence lifetime resolving power of the FLIM instrument. The spatial resolution (especially the high spatial frequencies not related to noise) of the FLIM image is preserved, because the denoising routine does not blur or smooth the image. By eliminating the random noise known to be specific to photon noise and from the intensifier amplification, the fidelity of the spatial resolution is improved. The polar plot projection, a rapid FLIM analysis method, is used to demonstrate the effectiveness of the denoising routine with exemplary data from both physical and complex biological samples. We also suggest broader impacts of the image analysis for other fluorescence microscopy techniques (e.g. super‐resolution imaging).
Microbiological risk for periodontitis of abutment teeth in patients with removable partial dentures
Authors: MINE K. , FUEKI K. , IGARASHI Y.
Published: July 2009

Summary  Tannerella forsythia, Porphyromonas gingivalis and Treponema denticola are identified as the red complex which exists in high proportions in periodontally diseased patients. The aim of this study was to assess the microbiological risk for periodontitis of abutment teeth in subjects wearing removable partial dentures (RPDs) by measuring the red complex using BANA‐ZymeTM test. Thirty‐eight subjects (mean age: 62·2 years) with Kennedy Class II partially edentulous arch participated in this study. The red complex and clinical parameters, such as plaque index, gingival index, probing depth and tooth mobility were recorded at abutment teeth in contact with the direct retainer of unilaterally designed RPDs and the corresponding non‐abutment teeth on the opposite side. Mean scores for the red complex, plaque index, gingival index and tooth mobility of the abutment teeth were significantly greater than those of the non‐abutment teeth (P < 0·01). No significant mean difference in pocket depth was found between the abutment and non‐abutment teeth. Logistic regression analysis revealed that abutment teeth, high scores of plaque index and a maintenance interval longer than 6 months were significant predictors for positive red complex scores (P < 0·05). These results suggest that the microbiological risk for periodontitis of abutment teeth is greater than that for non‐abutment teeth in RPD wearers.
Different models of HBeAg seroconversion predicated by on‐treatment ALT and HBV DNA profiles
Authors: You Hong , Ma Hong , Liu Tianhui , Cong Min , Wang Ping , Ou Xiaojuan , Wang Xiaoming , Ren Jiangbo , Li Hongyi , Wang Baoen , Jia Jidong
Published: July 2009

Summary.  Pretreatment alanine transaminase (ALT) elevation may be used as a predictor for higher hepatitis B e antigen (HBeAg) seroconversion in chronic hepatitis B patients. However, the role of dynamic changes of on‐treatment ALT for seroconversion is unknown. A total of 170 naïve HBeAg‐positive chronic hepatitis B patients were treated with a nucleoside/nucleotide analogues (NA), either lamivudine, adefovir, entecavir, or telbivudine, for at least 2 years and followed up for 1 more year. Clinical characteristics were detected and analysed at baseline and at 3‐month intervals. On‐treatment ALT predicted HBeAg seroconversion more accurately than baseline ALT. Among the patients with on‐treatment ALT ≤1 × UNL, 1–≤2 × UNL, 2–≤5 × UNL and >5 × UNL, HBeAg seroconversion was 11.4, 5.4, 24.4 and 65.0% (odds ratio = 1.0, 0.4, 2.5 and 14.4, respectively), respectively. Moreover, two models/types of seroconversion were observed. Type I was characterized by rapidly decreased ALT and HBV DNA during the first 3‐month interval, but with high HBeAg reversion rate (50%) after consolidation treatment. Type II was a slow decreased DNA procedure accompanied by significant elevated ALT with less reversion (23%). Receiver operating characteristic curve analysis showed a 1.9‐fold increased ALT ratio (present visit ALT: previous visit ALT) accompanied by at least a 0.8 log decreased HBV DNA may be used to classify these two seroconversion types. We conclude that on‐treatment elevated ALT levels is a better predictor for seroconversion after NAs treatment, and HBV DNA profiles may help to identify different models of seroconversion.
Effect of improved home ventilation on asthma control and house dust mite allergen levels
Authors: Wright G. R. , Howieson S. , McSharry C. , McMahon A. D. , Chaudhuri R. , Thompson J. , Donnelly I. , Brooks R. G. , Lawson A. , Jolly L. , McAlpine L. , King E. M. , Chapman M. D. , Wood S. , Thomson N. C.
Published: July 2009

Background:  The warm, humid environment in modern homes favours the dust mite population, but the effect of improved home ventilation on asthma control has not been established. We tested the hypothesis that a domestic mechanical heat recovery ventilation system (MHRV), in addition to allergen avoidance measures, can improve asthma control by attenuating re‐colonization rates.

Methods:  We conducted a randomized double‐blind placebo‐controlled parallel group trial of the installation of MHRV activated in half the homes of 120 adults with asthma, allergic to Dermatophagoides pteronyssinus. All homes had carpets steam cleaned and new bedding and mattress covers at baseline. The primary outcome was morning peak expiratory flow (PEF) at 12 months.

Results:  At 12 months, the primary end‐point; change in mean morning PEF as compared with baseline, did not differ between the MHRV group and the control group (mean difference 13.5 l/min, 95% CI: −2.6 to 29.8, P = 0.10). However, a secondary end‐point; evening mean PEF, was significantly improved in the MHRV group (mean difference 24.5 l/min, 95% CI: 8.9–40.1, P = 0.002). Indoor relative humidity was reduced in MHRV homes, but there was no difference between the groups in Der p 1 levels, compared with baseline.

Conclusions:  The addition of MHRV to house dust mite eradication strategies did not achieve a reduction in mite allergen levels, but did improve evening PEF.
Use of Argatroban during multi‐organ procurement: pharmacokinetics and sequelae in recipient of transplanted liver
Authors: Schwartz J.J. , Hatch J.M. , Book Z. , Lonardo N. , Hutson W.R. , Sorensen J.B.
Published: July 2009

Abstract:  This report illustrates potential concerns regarding the administration of Argatroban (AGN), a small molecule, direct thrombin inhibitor, within the setting of multi‐organ procurement (MOP). Herein, we outline the case of a large AGN bolus to the donor during MOP, and the passive transfer of a coagulopathy to the recipient of the transplanted liver. From this, we conclude that caution should be exercised when AGN is used in the setting of MOP.
Non‐invasive ventilation in do‐not‐intubate patients: five‐year follow‐up on a two‐year prospective, consecutive cohort study
Authors: BÜLOW H.‐H. , THORSAGER B.
Published: July 2009

Background: End‐of‐life decisions are common in intensive care units (ICUs), and increasingly, non‐invasive ventilation (NIV) is used as a ceiling of ventilatory care. However, little is known about the outcome following that decision.

Methods: An observational, single‐center, retrospective, follow‐up study with no interventions, on ICU patients treated with NIV and a do‐not‐intubate (DNI) order. The patients were followed until a 5‐year survival rate could be calculated.

Results: One hundred and fifty‐seven patients were treated with NIV during 2002 and 2003, and among 38 a DNI order was in effect. Of the 38 DNI patients, 11 died in the ICU, 16 died on the ward and 11 survived the hospital stay. Five of these 11 survivors died within 6 months, two died after 2.7 and 3.3 years, respectively, but four were still alive after 5 years. The long‐term (>6 months) survivors have, surprisingly only been admitted to the hospital 0–2 times a year – and seldom with the need for ICU treatment.

Conclusions: According to this study, and previous ones, it seems worthwhile treating DNI patients with NIV. Twenty‐five to 35% leave the hospital alive, every 6th patient lives for at least 1 year, and this paper shows that 10% may survive for 5 years or more. However, only chronic obstructive pulmonary disease and chronic heart failure patients (both with a concomitant low APACHE score) seem to have a reasonable outcome, and patients should be informed about this. So far, no study has investigated the quality of life of these survivors.
A controlled rapid‐sequence induction technique for infants may reduce unsafe actions and stress
Authors: EICH C. , TIMMERMANN A. , RUSSO S. G. , CREMER S. , NICKUT A. , STRACK M. , WEISS M. , MÜLLER M. P.
Published: July 2009

Background: Classic rapid‐sequence induction of anaesthesia (RSI‐classic) in infants and small children presents a time‐critical procedure, regularly associated with hypoxia. This results in high stress levels for the provider and may trigger unsafe actions. Hence, a controlled induction technique (RSI‐controlled) that involves gentle mask ventilation until full non‐depolarizing muscular blockade has become increasingly popular. Clinical observation suggests that RSI‐controlled may reduce the adverse effects noted above. We aimed to evaluate both techniques with respect to unsafe actions and stress.

Methods: In this controlled, randomized simulator‐based study, 30 male trainees and specialists in anaesthesiology performed a simulated anaesthesia induction in a 4‐week‐old infant with pyloric stenosis. Two different RSI techniques, classic and controlled, were applied to 15 candidates each. We recorded the incidence of hypoxaemia, forced mask ventilation, and intubation difficulties. In addition, we measured individual stress levels by ergospirometry, salivary cortisol, and α‐amylase, as well as a post‐trial questionnaire.

Results: Hypoxaemia always occurred in RSI‐classic but not in RSI‐controlled, repeatedly resulting in unsafe actions. Subjective stress perception and some objective stress levels were lower in the volunteers performing RSI‐controlled.

Conclusions: Our data suggest that RSI‐controlled, as compared with RSI‐classic, leads to fewer unsafe actions and may reduce individual stress levels.
Short‐Term Undernutrition Affects Final Development of Ovulatory Follicles in Sheep Synchronized for Ovulation
Authors: Sosa C , Gonzalez‐Bulnes A , Abecia JA , Forcada F , Meikle A
Published: July 2009

Contents

The objective of this study was to determine, in sheep, the effect of a short‐term undernutrition on growth dynamics and competence of pre‐ovulatory follicles. Synchronization of sexual cycles and induction of ovulation were performed, with progestagens and gonadotrophins, in 14 adult female sheep. Morphological characteristics and developmental competence of ovarian follicles to achieve ovulation were determined by imaging techniques (ultrasonography and laparoscopy) and blood sampling. All the animals ovulated and mean ovulation rates were similar between groups (2.0 ± 0.6 corpora lutea in control ewes and 2.2 ± 0.8 in undernourished sheep). However, nutritional restriction, even during a short period, was related to the presence of large follicles in static growing phase which, despite reaching ovulation, persisted static during the induced follicular phase and evidenced functional alterations as there was no inhibition of the development of subordinate follicles. Thus, this study suggests the existence of deleterious effects from short‐term undernutrition on functionality of pre‐ovulatory follicles, which can compromise fertility.
Comparative efficacy of thalidomide and prednisolone in the treatment of moderate to severe erythema nodosum leprosum: A randomized study
Authors: Kaur Inderjeet , Dogra Sunil , Narang Tarun , De Dipankar
Published: July 2009

The present study was undertaken to compare the efficacy and safety of thalidomide to that of oral prednisolone in the treatment of moderate to severe type 2 lepra reaction. Sixty patients with a histologically confirmed diagnosis of erythema nodosum leprosum with a clinical score of 4 or more (i.e. moderate to severe type 2 reaction) were randomly allocated to two groups comprising 30 patients each. Group 1 patients were given thalidomide at a dose of 300 mg/day for 1 week and the dose was gradually reduced, and Group 2 received prednisolone 40 mg daily for 2 weeks, which was tapered by 10 mg every 2 weeks. Thalidomide induced a faster clinical response (cutaneous as well as systemic) compared with prednisolone. Patients taking thalidomide had fewer relapses and a longer period of remission than those receiving prednisolone.
Vitiligo‐like depigmentation induced by imiquimod treatment of superficial basal cell carcinoma
Authors: Sriprakash Kavita , Godbolt Amanda
Published: July 2009

A 61‐year‐old man was treated with imiquimod 5% cream for superficial basal cell carcinoma, five times per week for 13 weeks. This resulted in vitiligo‐like depigmentation and poliosis in the area of treatment. This rare side‐effect has been noted in previous case reports of imiquimod treatment for both genital warts and superficial basal cell carcinoma. This highlights the importance of such a side‐effect being discussed with the patient who is to be treated with imiquimod, particularly in cosmetically sensitive areas.