bluuebunny/crossref_metadata_2025 huggingface dataset:
Tuning thermal conductivity of nanoporous crystalline silicon by surface passivation: A molecular dynamics study
Authors: Fang Jin , Pilon Laurent
Published: July 2012

Surface passivation of nanoporous crystalline silicon can reduce its thermal conductivity. This was established using equilibrium molecular dynamics simulations. The porosity varied from 8% to 38% while the pore diameter ranged from 1.74 to 2.93 nm. Hydrogen and oxygen passivation reduced thermal conductivity by 11% to 17% and 37% to 51% depending on porosity at 500 K, respectively. The hydrogen passivation effect decreased with increasing temperature. Vibrational spectra of oxygen overlapped with those of silicon at low frequencies. Therefore, oxygen passivation enhanced phonon scattering at solid matrix boundaries, resulting in stronger thermal conductivity reduction than that caused by hydrogen passivation.
Numerical analysis of indirect Auger transitions in InGaN
Authors: Bertazzi Francesco , Goano Michele , Bellotti Enrico
Published: July 2012

Indirect phonon-assisted Auger recombination mechanisms in bulk InGaN are investigated in the framework of perturbation theory, using first-principles phonon spectral density functions and electronic structures obtained by nonlocal empirical pseudopotential calculations. Nonpolar carrier-phonon interactions are treated within the rigid pseudoion framework, thus avoiding the introduction of empirical deformation potentials. The calculated indirect Auger coefficients exhibit a weak temperature dependence and dominate over direct processes for alloy compositions corresponding to the entire visible spectrum. The present results suggest that indirect Auger processes may be relevant in the operation of InGaN-based light-emitting diodes and lasers, at least in the yellow-green spectral region.
Nonlinear conductance quantization effects in CeOx/SiO2-based resistive switching devices
Authors: Miranda E. , Kano S. , Dou C. , Kakushima K. , Suñé J. , Iwai H.
Published: July 2012

The electron transport in W/CeOx/SiO2/NiSi2 resistive switching devices fabricated onto a p+-type Si substrate is investigated. It is shown that the structures exhibit bipolar switching with conductance values in the low resistance state (LRS) close to integer and half integer values of the quantum unit G0 = 2e2/h, e and h being the electron charge and Planck constant, respectively. This behavior is consistent with the so-called nonlinear conduction regime in quantum point-contacts. A simple model for the LRS current-voltage characteristic based on the finite-bias Landauer formula which accounts for the right- and left-going conduction modes dictated by the constriction’s cross-section area and the voltage drop distribution along the filamentary path is reported.
Analyses of hetero-interface trapping properties in AlGaN/GaN high electron mobility transistor heterostructures grown on silicon with thick buffer layers
Authors: Freedsman Joseph J. , Kubo Toshiharu , Egawa Takashi
Published: July 2012

We report on the analyses of trapping properties of metal-organic chemical vapor deposition grown AlGaN/GaN high-electron-mobility transistor (HEMT) heterostructures on silicon with increasing buffer thickness (Tbuff). An exact exponential dependence of AlGaN/GaN hetero-interface trap time constants with gate bias was observed in the vicinity of threshold voltage. A low hetero-interface state density (Dit) value of ∼2.5 × 1010 cm−2 eV−1 was achieved for heterostructures grown by using thick Tbuff ∼ 5 μm against a Dit value of ∼1 × 1011 cm−2 eV−1 for a similar heterostructures grown with thin Tbuff ∼ 1.25 μm. Further, the high resolution x-ray rocking curve and Van der Pauw-Hall measurements also confirmed that increasing the Tbuff improves the AlGaN/GaN HEMT heterostructures with reduced edge dislocation densities and enhanced carrier transport properties.
Misfit dislocation gettering by substrate pit-patterning in SiGe films on Si(001)
Authors: Grydlik Martyna , Boioli Francesca , Groiss Heiko , Gatti Riccardo , Brehm Moritz , Montalenti Francesco , Devincre Benoit , Schäffler Friedrich , Miglio Leo
Published: July 2012

We show that suitable pit-patterning of a Si(001) substrate can strongly influence the nucleation and the propagation of dislocations during epitaxial deposition of Si-rich Si1-xGex alloys, preferentially gettering misfit segments along pit rows. In particular, for a 250 nm layer deposited by molecular beam epitaxy at xGe = 15%, extended film regions appear free of dislocations, by atomic force microscopy, as confirmed by transmission electron microscopy sampling. This result is quite general, as explained by dislocation dynamics simulations, which reveal the key role of the inhomogeneous distribution in stress produced by the pit-patterning.
High-pressure neutron study of the morphotropic lead-zirconate-titanate: Phase transitions in a two-phase system
Authors: Frantti J. , Fujioka Y. , Zhang J. , Wang S. , Vogel S. C. , Nieminen R. M. , Asiri A. M. , Zhao Y. , Obaid A. Y. , Mkhalid I. A.
Published: July 2012

The present study was dedicated to the classical piezoelectric, lead-zirconate-titanate ceramic with composition Pb(Zr0.54Ti0.46)O3 at the Zr-rich side of the morphotropic phase boundary at which two phases co-exists. The pressure-induced changes in the phase fractions were studied by high-pressure neutron powder diffraction technique up to 3 GPa and 773 K. The two co-existing phases were rhombohedral R3c and monoclinic Cm at room temperature and R3c and P4mm above 1 GPa and 400 K. The experiments show that pressure favors the R3c phase over the Cm and P4mm phases, whereas at elevated temperatures entropy favours the P4mm phase. At 1 GPa pressure, the transition to the cubic Pm3¯m phase occurred at around 600 K. Pressure lowers the Cm→P4mm transition temperature. The Cm phase was found to continuously transform to the P4mm phase with increasing pressure, which is inline with the usual notion that the hydrostatic pressure favours higher symmetry structures. At the same time, the phase fraction of the R3c phase was increasing, implying discontinuous Cm→R3c phase transition. This is in clear contrast to the polarization rotation model according to which the Cm would link the tetragonal and rhombohedral phases by being a phase in which the polarization would, more or less continuously, rotate from the tetragonal polarization direction to the rhombohedral direction. Pressure induces large changes in phase fractions contributing to the extrinsic piezoelectricity. The changes are not entirely reversible, as was revealed by noting that after high-pressure experiments the amount of rhombohedral phase was larger than initially, suggesting that on the Zr-rich side of the phase boundary the monoclinic phase is metastable. An important contribution to the intrinsic piezoelectricity was revealed: a large displacement of the B cations (Zr and Ti) with respect to the oxygen anions is induced by pressure.
Sharp acoustic multipolar-resonances in highly monodisperse emulsions
Authors: Brunet Thomas , Raffy Simon , Mascaro Benoit , Leng Jacques , Wunenburger Régis , Mondain-Monval Olivier , Poncelet Olivier , Aristégui Christophe
Published: July 2012

We report the achievement of highly monodisperse emulsions exhibiting about ten acoustic Mie resonances. Thanks to robotics, the effective acoustic properties of such strongly scattering media can be precisely targeted by means of the production of calibrated (random) liquid-droplets. Ultrasonic experiments are compared, with an excellent quantitative agreement, to theoretical predictions derived within the framework of the independent scattering approximation. The dependence of the sound speed and of the acoustic attenuation on both the size and the volume fraction of droplets is quantitatively examined for dilute and more concentrated emulsions, and is presented in a dimensionless way.
Incorporating habitat preference into the stock assessment and management of blue marlin (Makaira nigricans) in the Pacific Ocean
Authors: Su Nan-Jay , Sun Chi-Lu , Punt André E. , Yeh Su-Zan , DiNardo Gerard
Published: July 2012

Stock assessments that include a spatial component or relate population dynamics to environmental conditions can be considered one way of implementing an ecosystem approach to fisheries. A spatially-structured population dynamics model that takes account of habitat preference is developed and then applied to Pacific blue marlin (Makaira nigricans), as they prefer certain habitats and migrate seasonally. The model is fitted to fishery catch-rate and size data, along with information on the relative density of the population over space derived from a habitat preference model fitted to oceanographic and biological variables. Results show that blue marlin are more abundant in tropical waters, and females account for most of the biomass. Assessments that allow for environmental factors, movement dynamics and sexual dimorphism indicate that this population is in an over-exploited state, with current spawning stock biomass below the level corresponding to maximum sustainable yield (SMSY) and current fishing mortality exceeding that needed to achieve MSY (FMSY). A risk analysis based on samples from a Bayesian posterior distribution suggests that the population will remain above SMSY after 20 years if exploitation rates are below the level corresponding to FMSY.
Exploiting seasonal habitat use of the common carp, Cyprinus carpio, in a lacustrine system for management and eradication
Authors: Taylor Andrew H. , Tracey Sean R. , Hartmann Klaas , Patil Jawahar G.
Published: July 2012

The control of invasive species is a major challenge to the preservation of native ecosystems, both terrestrial and aquatic. A population of the invasive common carp, Cyprinus carpio, was detected in Lakes Sorell and Crescent, Tasmania, Australia, in the mid-1990s. Early detection allowed for the containment of their population to this lacustrine system. Radio-telemetry was subsequently used over a 5-year period to understand seasonal distribution of carp in relation to environmental parameters to guide efficient eradication strategies. The present study found that fish displayed increased mobility during spring–summer periods, moving into shallow habitat rich in macrophytes, particularly during years of high lake levels. During years of low lake levels, this pattern was altered with frequent use of a rocky ‘secondary’ habitat in Lake Sorell. During winter, carp congregated in deeper habitat in Lake Sorell, whereas no habitat-specific winter aggregations were found in Lake Crescent. The increased knowledge of spatio-temporal preferences of carp provided a basis for deploying barriers to facilitate the capture of fish and sabotage spawning events. The results have led to the eradication of carp from Lake Crescent and a significant reduction of their population in Lake Sorell.
Growth, morphometrics and size structure of the Diadematidae sea urchin Centrostephanus rodgersii in northern New Zealand
Authors: Pecorino Danilo , Lamare Miles D. , Barker Mike F.
Published: July 2012

The sea urchin Centrostephanus rodgersii has increased its range in Eastern Australia resulting in important ecological changes. C. rodgersii may also have expanded its distribution range to northern New Zealand in the last five to six decades, although little is known about this process and of the biology of the species in New Zealand. We investigated morphometrics as well as growth using two techniques (growth line count in genital plates and tag–recapture using the fluorescent marker tetracycline). These methods allowed modelling of size at age of C. rodgersii in New Zealand, which we compared with populations recently established in Tasmania. The modelled growth rate was only slightly higher in the New Zealand population, and no differences in morphometrics were observed. The New Zealand population structure suggests that annual recruitment occurs regularly, with the population including a range of ages (3 to 10+ years).
Bacterial swimmers that infiltrate and take over the biofilm matrix
Authors: Houry Ali , Gohar Michel , Deschamps Julien , Tischenko Ekaterina , Aymerich Stéphane , Gruss Alexandra , Briandet Romain
Published: July 2012

Bacteria grow in either planktonic form or as biofilms, which are attached to either inert or biological surfaces. Both growth forms are highly relevant states in nature and of paramount scientific focus. However, interchanges between bacteria in these two states have been little explored. We discovered that a subpopulation of planktonic bacilli is propelled by flagella to tunnel deep within a biofilm structure. Swimmers create transient pores that increase macromolecular transfer within the biofilm. Irrigation of the biofilm by swimmer bacteria may improve biofilm bacterial fitness by increasing nutrient flow in the matrix. However, we show that the opposite may also occur (i.e., swimmers can exacerbate killing of biofilm bacteria by facilitating penetration of toxic substances from the environment). We combined these observations with the fact that numerous bacteria produce antimicrobial substances in nature. We hypothesized and proved that motile bacilli expressing a bactericide can also kill a heterologous biofilm population,
Staphylococcus aureus
in this case, and then occupy the newly created space. These findings identify microbial motility as a determinant of the biofilm landscape and add motility to the complement of traits contributing to rapid alterations in biofilm populations.
β-Arrestin2 mediates the initiation and progression of myeloid leukemia
Authors: Fereshteh Mark , Ito Takahiro , Kovacs Jeffrey J. , Zhao Chen , Kwon Hyog Young , Tornini Valerie , Konuma Takaaki , Chen Minyong , Lefkowitz Robert J. , Reya Tannishtha
Published: July 2012

β-Arrestins were initially discovered as negative regulators of G protein-coupled receptor signaling. Although β-arrestins have more recently been implicated as scaffold proteins that interact with various mitogenic and developmental signals, the genetic role of β-arrestins in driving oncogenesis is not known. Here we have investigated the role of β-arrestin in hematologic malignancies and have found that although both β-arrestin1 and -2 are expressed in the hematopoietic system, loss of β-arrestin2 preferentially leads to a severe impairment in the establishment and propagation of the chronic and blast crisis phases of chronic myelogenous leukemia (CML). These defects are linked to a reduced frequency, as well as defective self-renewal capacity of the cancer stem-cell population, in mouse models and in human CML patient samples. At a molecular level, the loss of β-arrestin2 leads to a significant inhibition of β-catenin stabilization, and ectopic activation of Wnt signaling reverses the defects observed in the β-arrestin2 mutant cells. These data cumulatively show that β-arrestin2 is essential for CML disease propagation and indicate that β-arrestins and the Wnt/β-catenin pathway lie in a signaling hierarchy in the context of CML cancer stem cell maintenance.
Potential of GLMM in modelling invasive spread: literature analysis.
Authors: Thiele J. , Markussen B.
Published: July 2012

This paper, Supplement A to Thiele J, Markussen B. Potential of GLMM in modelling invasive spread. CAB Reviews 2012; 7:016, describes the literature search done as part of the analysis of generalized linear mixed models in the context of invasive spread.
Communicable diseases and the human-animal relationship - Mini Review.
Authors: Webber R.
Published: July 2012

Communicable diseases continue to be a major health problem especially in developing countries, with respiratory infections causing the greatest mortality. The method of transmission is the key to grouping similar infections and the focus for investigating new diseases. Several new infections have resulted in species transfer, as has occurred recently with influenza. Although restricted to a few countries and individuals coming in close contact with poultry, avian influenza A(H5N1) remains a continuing threat in that it might mutate with an existing strain of human influenza to produce a highly lethal infection.
Vitamin D: multiple sclerosis risk and disease severity.
Authors: Geldern G. von , Mowry E. M.
Published: July 2012

This review seeks to provide a summary of the current evidence examining the relationship between multiple sclerosis (MS) and vitamin D. Both the incidence and the severity of MS have been shown to be influenced by vitamin D levels. Herein, we summarize relevant epidemiological studies. We also provide an overview of the
in vitro
and animal model experiments that give biological plausibility to the relationship between vitamin D and MS. By providing an up-to-date review about this field, directions for further studies may also become clear.
Analysing the genetic basis of milk production traits.
Authors: Lopez-Villalobos N.
Published: July 2012

Genetic analyses of milk production traits have been based on a polygenic model that assumes that a trait is affected by an infinitesimal number of genes each with a very small effect. An updated review on the genetic parameters (heritabilities and genetic correlations) for milk components estimated using the polygenic model is provided in this review. There are many studies reporting estimates of genetic parameters for component yields of milk, fat and protein and concentrations of fat and protein. Few studies have considered lactose yield and percentage. A limited number of studies have reported estimates of genetic parameters for milk fat and protein composition. At the start of the new millennium, advances in DNA technology permitted the sequencing of bovine genome, the identification of large numbers of genetic markers across the genome in the form of single nucleotide polymorphisms (SNP) and the genotyping of thousands of these SNPs on individual animals at low costs. Based on these advances, genomic selection emerged as a new methodology to perform genetic analysis and estimate breeding values for milk production traits using genome-wide dense markers. Systems biology is becoming the new method to perform genetic analysis of milk production traits integrating results from genomics, transcriptomics, proteomics, metabolomics and bioinformatics studies. A conclusion from this review is that the genetic analysis of milk production traits has been changing dramatically during recent years from a polygenic infinitesimal model towards a systems biology approach.
The intensification of agroforestry by tree domestication for enhanced social and economic impact - Mini Review.
Authors: Leakey R. R. B.
Published: July 2012

Agroforestry can be used to improve the productivity of staple food crops by improving soil fertility and promoting agroecosystem function. The domestication of agroforestry trees producing marketable products then intensifies the agroforestry system and leads to marketing, trade and business opportunities that improve farmers' livelihood. Together, these steps provide a generic and adaptable model for more sustainable agriculture in the tropics, which builds on the success of, and enhances the outputs of, the Green Revolution.
Sleep or swim? Early‐morning training severely restricts the amount of sleep obtained by elite swimmers
Authors: Sargent Charli , Halson Shona , Roach Gregory Daniel
Published: July 2012

Good sleep is essential for optimal performance, yet few studies have examined the sleep/wake behaviour of elite athletes. The aim of this study was to assess the impact of early‐morning training on the amount of sleep obtained by world‐class swimmers. A squad of seven swimmers from the Australian Institute of Sport participated in this study during 14 days of high‐intensity training in preparation for the 2008 Olympic Games. During these 14 days, participants had 12 training days, each starting with a session at 06:00 h, and 2 rest days. For each day, the amount of sleep obtained by participants was determined using self‐report sleep diaries and wrist‐worn activity monitors. On nights that preceded training days, participants went to bed at 22:05 h (s=00:52), arose at 05:48 h (s=00:24) and obtained 5.4 h (s=1.3) of sleep. On nights that preceded rest days, participants went to bed at 00:32 h (s=01:29), arose at 09:47 h (s=01:47) and obtained 7.1 h (s=1.2) of sleep. Mixed model analyses revealed that on nights prior to training days, bedtimes and get‐up times were significantly earlier (p<0.001), time spent in bed was significantly shorter (p<0.001) and the amount of sleep obtained was significantly less (p<0.001), than on nights prior to rest days. These results indicate that early‐morning training sessions severely restrict the amount of sleep obtained by elite athletes. Given that chronic sleep restriction of <6 h per night can impair psychological and physiological functioning, it is possible that early‐morning schedules actually limit the effectiveness of training.
Identification of ILK as a new partner of the ADAM12 disintegrin and metalloprotease in cell adhesion and survival
Authors: Leyme Anthony , Bourd-Boittin Katia , Bonnier Dominique , Falconer Anaïs , Arlot-Bonnemains Yannick , Théret Nathalie
Published: July 2012

Based on its shedding and binding activities, the disintegrin and metalloprotease 12 (ADAM12) has been implicated in cell signaling. Here we investigate the intracellular protein interaction network of the transmembrane ADAM12L variant using an integrative approach. We identify the integrin-linked kinase (ILK) as a new partner for ADAM12L cellular functions. We demonstrate that ADAM12L coimmunoprecipitates with ILK in cells and that its cytoplasmic tail is required for this interaction. In human cultured hepatic stellate cells (HSCs), which express high levels of endogenous ADAM12L and ILK, the two proteins are redistributed to focal adhesions upon stimulation of a β1 integrin–dependent pathway. We show that down-regulation of ADAM12L in HSCs leads to cytoskeletal disorganization and loss of adhesion. Conversely, up-regulation of ADAM12L induces the Akt Ser-473 phosphorylation-dependent survival pathway via stimulation of β1 integrins and activation of phosphoinositide 3-kinase (PI3K). Depletion of ILK inhibits this effect, which is independent of ADAM12L proteolytic activity and involves its cytoplasmic domain. We further demonstrate that overexpression of ADAM12L promotes kinase activity from ILK immunoprecipitates. Our data suggest a new role for ADAM12L in mediating the functional association of ILK with β1 integrin to regulate cell adhesion/survival through a PI3K/Akt signaling pathway.
Rab27 effector Slp2-a transports the apical signaling molecule podocalyxin to the apical surface of MDCK II cells and regulates claudin-2 expression
Authors: Yasuda Takao , Saegusa Chika , Kamakura Sachiko , Sumimoto Hideki , Fukuda Mitsunori
Published: July 2012

Most cells in tissues are polarized and usually have two distinct plasma membrane domains—an apical membrane and a basolateral membrane, which are the result of polarized trafficking of proteins and lipids. However, the mechanism underlying the cell polarization is not fully understood. In this study, we investigated the involvement of synaptotagmin-like protein 2-a (Slp2-a), an effector molecule for the small GTPase Rab27, in polarized trafficking by using Madin–Darby canine kidney II cells as a model of polarized cells. The results show that the level of Slp2-a expression in MDCK II cells increases greatly as the cells become polarized and that its expression is specifically localized at the apical membrane. The results also reveal that Slp2-a is required for targeting of the signaling molecule podocalyxin to the apical membrane in a Rab27A-dependent manner. In addition, ezrin, a downstream target of podocalyxin, and ERK1/2 are activated in Slp2-a–knockdown cells, and their activation results in a dramatic reduction in the amount of the tight junction protein claudin-2. Because both Slp2-a and claudin-2 are highly expressed in mouse renal proximal tubules, Slp2-a is likely to regulate claudin-2 expression through trafficking of podocalyxin to the apical surface in mouse renal tubule epithelial cells.
The centriolar satellite proteins Cep72 and Cep290 interact and are required for recruitment of BBS proteins to the cilium
Authors: Stowe Timothy R. , Wilkinson Christopher J. , Iqbal Anila , Stearns Tim
Published: July 2012

Defects in centrosome and cilium function are associated with phenotypically related syndromes called ciliopathies. Centriolar satellites are centrosome-associated structures, defined by the protein PCM1, that are implicated in centrosomal protein trafficking. We identify Cep72 as a PCM1-interacting protein required for recruitment of the ciliopathy-associated protein Cep290 to centriolar satellites. Loss of centriolar satellites by depletion of PCM1 causes relocalization of Cep72 and Cep290 from satellites to the centrosome, suggesting that their association with centriolar satellites normally restricts their centrosomal localization. We identify interactions between PCM1, Cep72, and Cep290 and find that disruption of centriolar satellites by overexpression of Cep72 results in specific aggregation of these proteins and the BBSome component BBS4. During ciliogenesis, BBS4 relocalizes from centriolar satellites to the primary cilium. This relocalization occurs normally in the absence of centriolar satellites (PCM1 depletion) but is impaired by depletion of Cep290 or Cep72, resulting in defective ciliary recruitment of the BBSome subunit BBS8. We propose that Cep290 and Cep72 in centriolar satellites regulate the ciliary localization of BBS4, which in turn affects assembly and recruitment of the BBSome. Finally, we show that loss of centriolar satellites in zebrafish leads to phenotypes consistent with cilium dysfunction and analogous to those observed in human ciliopathies.
Survey estimates of king crab (Paralithodes camtschaticus) abundance off Northern Norway using GLMs within a mixed generalized gamma-binomial model and Bayesian inference
Authors: Hvingel C. , Kingsley M. C. S. , Sundet J. H.
Published: July 2012

Hvingel, C., Kingsley, M.C.S., and Sundet, J.H. 2012. Survey estimates of king crab (Paralithodes camtschaticus) abundance off Northern Norway using GLMs within a mixed generalized gamma-binomial model and Bayesian inference. – ICES Journal of Marine Science, 69: . A trawl survey provides information on number and biomass of introduced king crab (Paralithodes camtschaticus) to the management of a fishery off the coast of Northern Norway; the annual catch quotas are largely set as a percentage of the survey estimate. A specially built sledge trawl was designed for the survey. It needs only small areas of trawlable bottom, performs well on a wide range of bottoms, and appears to have good catchability for benthic organisms. Many survey hauls catch no crabs and the non-zero catches have a highly skewed distribution. Data were therefore analysed with a compound model, in which separate predictors were fitted for the proportion of zero catches and for the catch size of the non-zero catches. The compound model was fitted by Bayesian methods using WinBUGS. The distribution of non-zero catches fitted well to a generalized gamma distribution, but with parameter values that made it approximate a lognormal distribution. Numbers of fishable crabs peaked in 2003, and total numbers in 2010 were about two-fifths of the 2003 maximum.
Effects of a multi‐component responsible beverage service programme on violent assaults in Sweden
Authors: Trolldal Björn , Brännström Lars , Paschall Mallie J. , Leifman Håkan
Published: July 2012

Aim

A multi‐component Responsible Beverage Service (RBS) programme has been disseminated in Swedish municipalities. The aim of the programme is to reduce violence associated with consumption of alcohol at on‐licensed premises. This study aimed to analyse the effect of the programme on police‐recorded assaults after the dissemination of the programme in Swedish municipalities, 1996–2009.

Design

This study is a natural experiment that uses variation in the level of implementation of the RBS programme to predict change in the rate of police‐recorded assaults.

Setting

Swedish municipalities.

Participants

The municipalities included in the study initiated the RBS programme no later than 2008. On‐licensed premises open during the evenings must exist. Of 290 municipalities, 237 fulfilled these requirements.

Measurement

Programme fidelity was studied by means of several surveys. Yearly data on police‐recorded assaults, per 100 000 inhabitants aged 15 and above, committed on weekend nights, were used as dependent variable. A fixed‐effects panel data regression model was used to examine the effect of the programme.

Findings

Each extension of the programme, by one component, was associated with a significant 3.1% reduction in assaults. However, this effect was seen mainly in smaller municipalities. Of the different components of the programme, the presence of a community coalition steering group had a significant effect on assaults. No significant effect was found regarding RBS training or supervision of on‐licensed premises.

Conclusion

Multi‐component Responsible Beverage Service programmes can have a significant effect on police‐recorded assaults even when implemented on a large scale in many communities.
Effects of independent and substance‐induced major depressive disorder on remission and relapse of alcohol, cocaine and heroin dependence
Authors: Samet Sharon , Fenton Miriam C. , Nunes Edward , Greenstein Eliana , Aharonovich Efrat , Hasin Deborah
Published: July 2012

Aims

Little is known about the differential effects of independent and substance‐induced major depression on the longitudinal course of alcohol, cocaine and heroin disorders when studied prospectively.

Design

Consecutively admitted in‐patients, evaluated at baseline, 6‐, 12‐ and 18‐month follow‐ups.

Setting

Baseline evaluations in a short‐stay in‐patient urban community psychiatric hospital unit.

Participants

Adults (n = 250) with current DSM‐IV cocaine, heroin and/or alcohol dependence at baseline.

Measurements

The Psychiatric Research Interview for Substance and Mental Disorders (PRISM), used to evaluate independent and substance‐induced major depression, alcohol, cocaine and heroin dependence, and other psychiatric disorders. Outcomes for each substance: (i) time (weeks) from hospital discharge to first use; (ii) time from discharge to onset of sustained (≥26 weeks) remission from dependence; (iii) time from onset of sustained remission to relapse.

Findings

Substance‐induced major depression significantly predicted post‐discharge use of alcohol, cocaine and heroin (hazard ratios 4.7, 5.3 and 6.5, respectively). Among patients achieving stable remissions from dependence, independent major depression predicted relapse to alcohol and cocaine dependence (hazard ratios 2.3 and 2.7, respectively).

Conclusions

Substance‐induced and independent major depressions were both related to post‐discharge use of alcohol, cocaine and heroin. The findings suggest the importance of clinical attention to both types of depression in substance abusing patients.
Factors associated with pathways toward concurrent sex work and injection drug use among female sex workers who inject drugs in northern Mexico
Authors: Morris Meghan D. , Lemus Hector , Wagner Karla D. , Martinez Gustavo , Lozada Remedios , Gómez Rangel María Gudelia , Strathdee Steffanie A.
Published: July 2012

Aims

To identify factors associated with time to initiation of (i) sex work prior to injecting drugs initiation; (ii) injection drug use prior to sex work initiation; and (iii) concurrent sex work and injection drug use (i.e. initiated at the same age) among female sex workers who currently inject drugs (FSW–IDU).

Design

Parametric survival analysis of baseline data for time to initiation event.

Setting

Tijuana and Ciudad Juarez situated on the Mexico–US border.

Participants

A total of 557 FSW–IDUs aged ≥18 years.

Measurements

Interview‐administered surveys assessing context of sex work and injection drug use initiation.

Findings

Nearly half (n = 258) initiated sex work prior to beginning to inject, a third (n = 163) initiated injection first and a quarter (n = 136) initiated both sex work and injection drug use concurrently. Low education and living in Ciudad Juarez accelerated time to sex work initiation. Being from a southern Mexican state and initiating drug use with inhalants delayed the time to first injection drug use. Having an intimate partner encourage entry into sex work and first injecting drugs to deal with depression accelerated time to initiating sex work and injection concurrently. Early physical abuse accelerated time to initiating sex work and injection, and substantially accelerated time to initiation of both behaviors concurrently.

Conclusions

Among female sex workers who currently inject drugs in two Mexican–US border cities, nearly half appear to initiate sex work prior to beginning to inject, nearly one‐third initiate injection drug use before beginning sex work and one‐quarter initiate both behaviors concurrently. Predictors of these three trajectories differ, and this provides possible modifiable targets for prevention.
Red blood cell hypoxanthine phosphoribosyltransferase activity measured using 6‐mercaptopurine as a substrate: a population study in children with acute lymphoblastic leukaemia
Authors: LENNARD LYNNE , HALE JULIET P. , LILLEYMAN JOHN S.
Published: July 2012

6‐Mercaptopurine (6‐MP) is used in the continuing chemotherapy of childhood acute lymphoblastic leukaemia. The formation of red blood cell (RBC) 6‐thioguanine nucleotide (6‐TGN) active metabolites, not the dose of 6‐MP, is related to cytotoxicity and prognosis. But there is an apparent sex difference in 6‐MP metabolism. Boys require more 6‐MP than girls to produce the same range of 6‐TGN concentrations. Given the same dose, they experience fewer dose reductions because of cytotoxicity, and have a higher relapse rate.

The enzyme hypoxanthine phosphoribosyltransferase (HPRT) catalyses the initial activation step in the metabolism of 6‐MP to 6‐TGNs, a step that requires endogenous phosphoribosyl pyrophosphate (PRPP) as a cosubstrate. Both HPRT and the enzyme responsible for the formation of PRPP are X‐linked.

RBC HPRT activity was measured in two populations, 86 control children and 63 children with acute lymphoblastic leukaemia. 6‐MP was used as the substrate and the formation of the nucleotide product, 6‐thioinosinic acid (TIA) was measured. RBC 6‐TGN concentrations were measured in the leukaemic children at a standard dose of 6‐MP.

There was a 1.3 to 1.7 fold range in HPRT activity when measured under optimal conditions. The leukaemic children had significantly higher HPRT activities than the controls (median difference 4.2 μmol TIA ml−1 RBCs h−1, 95% C.I. 3.7 to 4.7, P < 0.0001). In the leukaemic children HPRT activity (range 20.4 to 26.6 μmol TIA ml−1 RBCs h−1, median 23.6) was not related to the production of 6‐TGNs (range 60 to 1,024 pmol 8 × 10−8 RBCs, median 323). RBC HPRT was present at a high activity even in those children with low 6‐TGN concentrations.

When HPRT is measured under optimal conditions it does not appear to be the metabolic step responsible for the observed sex difference in 6‐MP metabolism. This may be because RBC HPRT activity is not representative of other tissues but it could equally be because other sex‐linked factors are influencing substrate availability.
Inhibition of prostaglandin synthesis does not affect contractile responses to noradrenaline, serotonin, angiotensin II nor endothelin‐1 in human forearm isolated veins
Authors: CHIN JAYE P. F. , HURLSTON ROBYN M. , DART ANTHONY M.
Published: July 2012

The functional role of endogenous cyclo‐oxygenase products was examined in the human forearm isolated vein.

Six healthy normal adult males (age > 18 years old) were recruited. Forearm veins were biopsied and ring segments mounted in standard organ baths for recording of isometric force.

Noradrenaline (‐log molar EC50: 7.75 ± 0.19; –log molar threshold concentration: 8.80 ± 0.20), 5‐hydroxytryptamine (–log molar EC50: 7.52 ± 0.17; –log molar threshold concentration: 9.50 ± 0.64), angiotensin II (–log molar threshold concentration: 9.00 ± 0.28) and endothelin‐1 (–log molar threshold concentration: 9.13 ± 0.47) were equipotent in this preparation. Indomethacin (10 μ) had no effect on either the threshold concentration or EC50 of noradrenaline, 5‐hydroxytryptamine nor the threshold concentration of angiotensin II nor endothelin‐1.

Sodium nitroprusside (1 N‐10 μ) relaxed noradrenaline‐precontracted preparations. Evidence of minimal endothelial influence was confirmed by the lack of relaxant response to acetylcholine (1 N‐10 μ). Histology using silver staining confirmed that endothelial cells were absent over greater than 90% of the lumen surface.

We conclude that endogenous prostanoids derived from smooth muscle cells, either released basally or agonist‐stimulated, do not play a role in the regulation of vascular tone in the human forearm isolated vein.
A comparison of the acute haemodynamic effects of nisoldipine and nifedipine during treatment with atenolol in patients with coronary artery disease
Authors: DONALDSON KIRSTEEN M. , DAWKINS KEITH D. , WALLER DEREK G.
Published: July 2012

The acute haemodynamic effects of intravenous nisoldipine (1, 2, 4 μg kg−1) and nifedipine (2.5, 5, 10 μg kg−1) were compared in a randomised, within‐patient crossover study. Fifteen male patients with stable angina pectoris treated with atenolol were studied after undergoing routine cardiac catheterisation.

Nisoldipine caused a dose‐related fall in systemic vascular resistance (maximum 22%) associated with an increase in heart rate and cardiac index (18%) and a fall in mean arterial pressure (7%).

By contrast, nifedipine was associated with a significant increase in heart rate but systemic vascular resistance, cardiac index and mean arterial pressure remained unaltered.

At doses with equivalent effects on heart rate (2 μg kg−1 nisoldipine; 10 μg kg−1 nifedipine) acute dosing with nisoldipine caused a significantly greater fall in systemic vascular resistance and increase in cardiac index, whilst nifedipine caused a greater reduction in stroke volume index and left ventricular stroke work index.

The results suggest that, when combined with atenolol, acute dosing with nisoldipine may have a more complementary haemodynamic profile than nifedipine. The implications of this finding for chronic oral dosing in patients with impaired left ventricular function should be evaluated.
The antihypertensive efficacy and tolerability of a low dose combination of ramipril and felodipine ER in mild to moderate essential hypertension
Authors: BAINBRIDGE A. D. , MACFADYEN R. J. , STARK S. , LEES K. R. , REID J. L.
Published: July 2012

The antihypertensive efficacy and tolerability of a low dose combination of the angiotensin converting enzyme inhibitor ramipril (2.5 mg) and the extended release formulation of the dihydropyridine calcium channel antagonist felodipine (5 mg) were assessed in a double‐blind, double dummy placebo controlled, randomised, crossover study in 20 patients (mean age 55.4 years; range 46–69) with uncomplicated mild to moderate hypertension (supine diastolic >90 mmHg <115 mmHg after 4 weeks of single‐blind wash‐out on placebo). The four randomised, double‐blind, crossover study phases evaluated the response to 4 weeks of once daily treatment with placebo, monotherapy with each drug and the combination. Noninvasive ambulatory blood pressure monitoring (Spacelabs 90207) was performed for 24 h at the end of each phase.

The mean 24 h ambulatory blood pressure (mmHg) was 147.9/92.0 following placebo, 141.3/87.8 following monotherapy with ramipril 2.5 mg, 136.8/85.8 following monotherapy with felodipine ER 5 mg and 131.1/82.6 following the combination of ramipril 2.5 mg and felodipine ER 5 mg. All active treatment phases significantly reduced mean 24 h ambulatory diastolic pressure by comparison with placebo. The antihypertensive efficacy of the combination was additive.

The coadministration of ramipril did not attenuate the incidence of headache attributable to felodipine ER.
Post‐exercise reduction in blood pressure in hypertensive subjects: effects of angiotensin converting enzyme inhibition
Authors: BEAULIEU MARC , NADEAU ANDRÉ , LACOURCIÈRE YVES , CLÉROUX JEAN
Published: July 2012

Much attention has been given to the effects of various classes of antihypertensive drugs on blood pressure and haemodynamics. The effects of a single bout of exercise on post‐exercise blood pressure have also been studied by several investigators. However, the combined effects of prior exercise and antihypertensive medication has drawn less attention.

We examined the separate and combined effects of a single bout of exercise and of angiotensin converting enzyme (ACE) inhibition with a new ACE inhibitor (fosinopril, 20 mg day−1) on post‐exercise blood pressure and systemic and regional haemodynamics. Ten patients with mild‐to‐moderate hypertension were studied with a double‐blind, randomized crossover, placebo‐ and rest period‐controlled study design.

At rest, mean arterial pressure (MAP, −10 ± 2 mm Hg), total peripheral resistance (TPR, −11 ± 5%) and forearm vascular resistance (FVR, −17 ± 8%) were significantly (P < 0.05) reduced during ACE inhibition as compared with the placebo phase.

During the placebo phase, MAP (–3 ± 1 mm Hg), TPR (–10 ± 4%) and FVR (–9 ± 4%) were lower after exercise as compared with the control rest period.

During ACE inhibition, MAP (–3 ± 1 mm Hg) and TPR (–8 ± 4%) were lower, but FVR (+32 ± 15%) was increased after exercise as compared with the control rest period.

Thus, blood pressure and TPR decreased similarly after exercise during the placebo phase and during ACE inhibition. However, differences in post‐exercise forearm haemodynamics during the placebo phase and during ACE inhibition indicate that underlying regional haemodynamics are modified.
Differential effects of misoprostol and ranitidine on the pharmacokinetics of diclofenac and gastrointestinal symptoms
Authors: DAMMANN H. G. , SIMON‐SCHULTZ J. , STEINHOFF I. , DAMASCHKE A. , SCHMOLDT A. , SALLOWSKY E.
Published: July 2012

The effects of oral misoprostol (800 μg day−1) and ranitidine (300 mg day−1) on the pharmacokinetics of diclofenac (100 mg) were assessed in a three‐way randomized crossover study in 18 healthy male subjects.

Subjects were studied over three 8 day periods, during which they received twice‐daily placebo, misoprostol, or ranitidine. A single dose of diclofenac was given orally on days 1 and 8, and plasma diclofenac concentrations were measured by h.p.l.c. over 24 h.

Misoprostol caused a non‐significant 19% increase in the mean Cmax value of diclofenac on both days 1 and 8. After 8 days of dosing with misoprostol there was a significant (P = 0.04) 20% decrease in the AUC of diclofenac.

Ranitidine had no statistically significant effects on the pharmacokinetics of diclofenac.

Co‐administration of misoprostol and diclofenac was associated with a higher frequency and severity of gastrointestinal symptoms and frequency of bowel opening, and a decrease in faecal consistency when compared with either placebo or ranitidine plus diclofenac (P < 0.01).
Intramuscular picenadol in patients with postoperative pain
Authors: BRUNELLE ROCCO L. , GOLDSTEIN DAVID J. , GEORGE RICHARD E. , ZIMMERMAN DENNIS M.
Published: July 2012

The analgesic efficacy and safety of a single 50 mg intramuscular dose of rac‐picenadol, a centrally acting agonist‐antagonist opioid analgesic, were compared with pethidine (meperidine) 100 mg and placebo in 60 patients with moderate to severe postoperative pain using hourly pain intensity and relief measurements for up to 6 h following injection of the study medications.

Both picenadol and pethidine were statistically significantly (P < 0.05) more effective than placebo in reducing pain intensity and in increasing total relief. Patients receiving picenadol and pethidine had higher frequency of somnolence than patients receiving placebo. In addition, patients receiving picenadol 50 mg experienced a higher incidence of confusion (30%), speech disorders (30%), and tremors (25%) than the patients receiving either pethidine or placebo.

These results were compared with those of a similar study which investigated the effects of a 25 mg intramuscular dose of picenadol vs pethidine and placebo. This comparison suggests that 25 mg of picenadol is a more acceptable dosage since both 25 and 50 mg were effective dosages.
The pharmacokinetics of tranylcypromine enantiomers in healthy subjects after oral administration of racemic drug and the single enantiomers
Authors: WEBER‐GRANDKE H. , HAHN G. , MUTSCHLER E. , MÖHRKE W. , LANGGUTH P. , SPAHN‐LANGGUTH H.
Published: July 2012

The pharmacokinetics of the two enantiomers of tranylcypromine were evaluated in six healthy subjects after oral dosage of the racemate (20 mg of the sulphate) and the single enantiomers (10 mg of the sulphate) using an enantiospecific assay. Significant differences in AUC, Cmax, λz, and CLR of the two enantiomers were observed both on administration of the racemate and of the individual enantiomers. The plasma concentrations and urinary excretion rates of (–)‐tranylcypromine exceeded those of (+)‐tranylcypromine. AUCs of the (–)‐enantiomer [arithmetical means 197 ng ml−1 h after the racemate, 130 ng ml−1 h after the enantiomer] were greater than those of the (+)‐enantiomer [26 ng ml−1 h after the racemate, 28 ng ml−1 h after the enantiomer] (P = 0.0001). No in vivo racemisation was detected. The power of the study was insufficient to establish any enantiomer‐enantiomer interaction except for a possible interaction at the level of renal clearance (P = 0.013 for both enantiomers).
Absence of an inhibitory effect of omeprazole and nizatidine on phenytoin disposition, a marker of CYP2C activity
Authors: BACHMANN K. A. , SULLIVAN T. J. , JAUREGUI L. , REESE J. H. , MILLER K. , LEVINE L.
Published: July 2012

The effects of omeprazole (40 mg orally per day) and nizatidine (300 mg orally per day) on the disposition of phenytoin (4.5 mg kg−1 p.o. single dose) were studied in 18 healthy, young adult males. Total and unbound plasma concentrations of phenytoin were measured for 48 h after each dose of phenytoin. Neither treatment altered the disposition kinetics of phenytoin, the hydroxylation of which is mediated specifically by cytochromes P450 of the 2C subfamily.
Oral pharmacokinetics and food interaction of the leukotriene D4 receptor antagonist verlukast
Authors: SCHWARTZ JULES I. , MARGOLSKEE DOROTHY J. , BJORNSSON THORIR D. , WILLIAMS VANESSA C. , HSIEH JOHN Y. , LIN CHARLES C. , ROGERS J. DOUGLAS
Published: July 2012

The influence of dose and food on the pharmacokinetic profile of orally administered verlukast, a leukotriene D4 receptor antagonist, was investigated in 12 healthy male volunteers. This was an open, four‐period, single dose, randomised, crossover design including the following doses: one 75 mg tablet, one 250 mg tablet, 500 mg (2 × 250 mg) and 500 mg immediately following a standard meal. There were dose‐related increases in the AUC, although after 500 mg verlukast this was disproportionately greater than with 75 mg (P = 0.04). Similarly, there were dose‐related increases in Cmax. No differences were observed in the tmax between treatments. With respect to food, there was a 22% decrease (P = 0.02) in Cmax after 500 mg, and the AUC was 13% less (P = 0.052). The differences in the plasma concentration profiles betweeen fasted and fed states are not considered to be of clinical importance.