bluuebunny/crossref_metadata_2025 huggingface dataset:
Microstructural characterisation of novel 6351 Al–Al4SiC4in-situ composite
Authors: Mondal M K , Biswas K , Maity J
Published: October 2013

6351 Al–Al4SiC4 composite has been developed through stir casting route by incorporation of fine TiC powder in 6351 Al melt. Simultaneous effects of the generation of in-situ particles (Al4SiC4 and Al3Ti) and grain refinement were observed. The in-situ generated Al4SiC4 particles were found to act as nucleation sites for primary α (causing grain refinement) along with engulfment effect promoting uniform particle distribution. As the volume fraction of Al4SiC4 particles increased, the dendritic solidification was suppressed (more equiaxed grains appeared) and overall grain size of the matrix decreased. Besides, the precipitation of Al3Ti occurred at the dislocation enriched region. Accordingly, hardness of the composite was improved with increasing content of Al4SiC4 particles.
Effects of dynamic recrystallisation during deep rolling of semisolid slab and heat treatment on microstructure and properties of AZ31 alloy
Authors: Zhao Z. Y. , Guan R. G. , Wang X. , Dai C. G. , An C. G. , Liu C. M. , Lee C. S.
Published: October 2013

A novel process of manufacturing high performance AZ31 alloy strip was put forward by combining semisolid rolling, deep rolling and heat treatment, and the effects of dynamic recrystallisation during deep rolling of semisolid slab and heat treatment on microstructure and properties of AZ31 alloy were investigated. When the casting temperature was set from 650 to 690°C and the vibration frequency was controlled at 80 Hz, AZ31 alloy strip with the cross-section size of 4×160 mm and fine near round and rosette grains was manufactured by semisolid rolling. Dynamic recrystallisation happened during deep rolling process. Dynamic recrystallisation grain size decreases with the increase in deep rolling temperature in a certain scope. With the increase in deep rolling deformation amount, the microstructure evolved gradually from coarse primary grains and twins to fine dynamic recrystallisation grains and twist primary grains as well as small regular equiaxed grains. AZ31 alloy strip with very fine equiaxed grain in size of 6 μm was obtained by deep rolling. After solution treatment at 415°C for 20 h, the saturated solid solution of AZ31 alloy strip has been formed. After solution treatment at 415°C for 20 h and aging at 230°C for 16 h, the deep rolled AZ31 alloy strips exhibit excellent mechanical properties; the ultimate tensile strength, yield strength, elongation to failure and hardness could reach 330 MPa, 204 MPa, 11 and 71 HV respectively.
Preparation of ZnNi alloy films by electrodeposition
Authors: Yu Y. D. , Zhao X. X. , Li M. G. , Wei G. Y. , Sun L. X. , Fu Y.
Published: October 2013

ZnNi alloy films were electrodeposited from a kind of acid solution on a steel substrate. Influences of various temperatures on deposition rate, component, current density, anticorrosion performance and surface morphology were investigated. With the increase in temperatures, deposition rate increased and then declined gradually. Maximum deposition rate (85 mg h−1) was achieved when the temperature was equal to 313 K. Approximately 90% current efficiency was obtained at the temperature of 313 K. When the temperature was >313 K, drastic side reactions consumed certain part of total current, which would result in decrease in current efficiency. According to polarisation curves, ZnNi films with 12% nickel possessed the most positive corrosion potential (−0·81 V) and optimal anticorrosion performance. ZnNi alloy film obtained at the temperature of 293 K showed small nodular structures with even and smooth surface. With the increase in temperatures, rougher surface and bulk structures could be detected.
Nitrogen uptake by nickel in NH3–H2 atmospheres
Authors: Fonović M. , Leineweber A. , Mittemeijer E. J.
Published: October 2013

The incorporation of N into Ni[N] solid solution by gaseous nitriding in NH3-H2 containing atmospheres, corresponding to a nitriding potential rN,0 at the tube furnace inlet, was studied at 450°C. For the encountered low N contents cN (<1 at.-%), validity of Henry's law is expected, i.e. proportionality of cN with the nitriding potential rN,0 of the gas inserted into the furnace. However, NH3 decomposition in the furnace, even at the temperature considered, which is usually neglected, leads to deviation from this proportionality, i.e. an effective rN< rN,0 operates. A scheme for obtaining the cN( rN) data from the experimental cN( rN,0) data is described.
The CSF3R T618I mutation causes a lethal neutrophilic neoplasia in mice that is responsive to therapeutic JAK inhibition
Authors: Fleischman Angela G. , Maxson Julia E. , Luty Samuel B. , Agarwal Anupriya , Royer Lacey R. , Abel Melissa L. , MacManiman Jason D. , Loriaux Marc M. , Druker Brian J. , Tyner Jeffrey W.
Published: October 2013

Key Points

CSF3R T618I is sufficient to drive a lethal myeloproliferative disease in a mouse bone marrow transplant model. Treatment of CSF3R T618I mice with the JAK1/2 inhibitor ruxolitinib effectively reduces white blood cell count and spleen size.
An official American Thoracic Society and European Respiratory Society policy statement: disparities in respiratory health
Authors: Schraufnagel Dean E. , Blasi Francesco , Kraft Monica , Gaga Mina , Finn Patricia , Rabe Klaus F.
Published: October 2013

Health disparities, defined as a significant difference in health between populations, are more common for diseases of the respiratory system than for those of other organ systems, because of the environmental influence on breathing and the variation of the environment among different segments of the population. The lowest social groups are up to 14 times more likely to have respiratory diseases than are the highest. Tobacco smoke, air pollution, environmental exposures, and occupational hazards affect the lungs more than other organs and occur disproportionately in ethnic minorities and those with lower socioeconomic status. Lack of access to quality healthcare contributes to disparities.

The executive committees of the American Thoracic Society (ATS) and European Respiratory Society (ERS) established a writing committee to develop a policy on health disparities. The document was reviewed, edited, and approved by their full executive committees and boards of directors of the societies.

This document expresses a policy to address health disparities by promoting scientific inquiry and training, disseminating medical information and best practices, and monitoring and advocating for public respiratory health. The ERS and the ATS have strong international commitments and work with leaders from governments, academia, and other organisational bodies to address and reduce avoidable health inequalities. Their training initiatives improve the function of healthcare systems and health equality. Both the ATS and the ERS support all aspects of this document, confer regularly, and act together when possible, but the activities to bring about change may vary because of the differences in the continents where the two organisations carry out most of their activities.

The ATS and ERS pledge to frame their actions to reduce respiratory health disparities. The vision of the ATS and ERS is that all persons attain better and sustained respiratory health. They call on all their members and other societies to join in this commitment.
Increase in chemokines CXCL10 and CCL2 in blood from pigs infected with high compared to low virulence African swine fever virus isolates
Authors: Fishbourne Emma , Hutet Evelyne , Abrams Charles , Cariolet Roland , Le Potier Marie-Frédérique , Takamatsu Haru-H , Dixon Linda K
Published: October 2013

Modulation of the expression of chemokines and chemokine receptors in whole blood was compared following infection of pigs with high and low virulence isolates of African swine fever virus. Levels of mRNAs for CCL2, CCL3L1, CCL4, CXCL10, CCR1 and CCR5 were significantly increased in at least one time point following infection in two experiments and CCL5, CCR9 and CXCR4 mRNA were significantly increased in one of the experiments. The results showed that greatest fold increases in mRNAs for CXCL10 and CCL2 were observed following infection of pigs. CXCL10 mRNA was increased by up to 15 fold in infected compared to uninfected pigs. CXCL10 protein was also detected in serum from pigs infected with the high virulence Benin 97/1 isolate. Levels of CCL2 mRNA were increased in pigs infected with high virulence Benin 97/1 isolate compared to low virulence OURT88/3 isolate and this correlated with an increase of greater than 30 fold in levels of CCL2 protein detected in serum from pigs infected with this isolate. An increase in overall chemotaxis active compounds in defibrinated plasma samples from Benin 97/1 infected pigs was observed at 3 days post-infection (dpi) and a decrease by 7 dpi as measured by chemotaxis assay using normal pig leucocytesin vitro. Increased levels of CXCL10 may either contribute to the activation of lymphocyte priming toward the Th1 phenotype or induction of T lymphocyte apoptosis. Increased levels of CCL2, a chemoattractant for macrophages, may result in increased recruitment of monocytes from bone marrow thus increasing the pool of cells susceptible to infection.
Gut microbiota dysbiosis and bacterial community assembly associated with cholesterol gallstones in large-scale study
Authors: Wu Tao , Zhang Zhigang , Liu Bin , Hou Dezhi , Liang Yun , Zhang Jie , Shi Peng
Published: October 2013

Background

Elucidating gut microbiota among gallstone patients as well as the complex bacterial colonization of cholesterol gallstones may help in both the prediction and subsequent lowered risk of cholelithiasis. To this end, we studied the composition of bacterial communities of gut, bile, and gallstones from 29 gallstone patients as well as the gut of 38 normal individuals, examining and analyzing some 299, 217 bacterial 16S rRNA gene sequences from 120 samples.

Results

First, as compared with normal individuals, in gallstone patients there were significant (P < 0.001) increases of gut bacterial phylum Proteobacteria and decreases of three gut bacterial genera, Faecalibacterium, Lachnospira, and Roseburia. Second, about 70% of gut bacterial operational taxonomic units (OTUs) from gallstone patients were detectable in the biliary tract and bacteria diversity of biliary tract was significantly (P < 0.001) higher than that of gut. Third, analysis of the biliary tract core microbiome (represented by 106 bacteria OTUs) among gallstone patients showed that 33.96% (36/106) of constituents can be matched to known bacterial species (15 of which have publicly available genomes). A genome-wide search of MDR, BSH, bG, and phL genes purpotedly associated with the formation of cholesterol gallstones showed that all 15 species with known genomes (e.g., Propionibacterium acnes, Bacteroides vulgates, and Pseudomonas putida) contained at least contained one of the four genes. This finding could potentially provide underlying information needed to explain the association between biliary tract microbiota and the formation of cholesterol gallstones.

Conclusions

To the best of our knowledge, this is the first study to discover gut microbiota dysbiosis among gallstone patients, the presence of which may be a key contributor to the complex bacteria community assembly linked with the presence of cholesterol gallstones. Likewise, this study also provides the first large-scale glimpse of biliary tract microbiota potentially associated with cholesterol gallstones. Such a characterization of the biliary tract core microbiome has potentially important biological and medical implications regarding the role of bacteria in the formation cholesterol gallstones.
An evaluation of the PacBio RS platform for sequencing and de novo assembly of a chloroplast genome
Authors: Ferrarini Marco , Moretto Marco , Ward Judson A , Šurbanovski Nada , Stevanović Vladimir , Giongo Lara , Viola Roberto , Cavalieri Duccio , Velasco Riccardo , Cestaro Alessandro , Sargent Daniel J
Published: October 2013

Background

Second generation sequencing has permitted detailed sequence characterisation at the whole genome level of a growing number of non-model organisms, but the data produced have short read-lengths and biased genome coverage leading to fragmented genome assemblies. The PacBio RS long-read sequencing platform offers the promise of increased read length and unbiased genome coverage and thus the potential to produce genome sequence data of a finished quality containing fewer gaps and longer contigs. However, these advantages come at a much greater cost per nucleotide and with a perceived increase in error-rate. In this investigation, we evaluated the performance of the PacBio RS sequencing platform through the sequencing and de novo assembly of the Potentilla micrantha chloroplast genome.

Results

Following error-correction, a total of 28,638 PacBio RS reads were recovered with a mean read length of 1,902 bp totalling 54,492,250 nucleotides and representing an average depth of coverage of 320× the chloroplast genome. The dataset covered the entire 154,959 bp of the chloroplast genome in a single contig (100% coverage) compared to seven contigs (90.59% coverage) recovered from an Illumina data, and revealed no bias in coverage of GC rich regions. Post-assembly the data were largely concordant with the Illumina data generated and allowed 187 ambiguities in the Illumina data to be resolved. The additional read length also permitted small differences in the two inverted repeat regions to be assigned unambiguously.

Conclusions

This is the first report to our knowledge of a chloroplast genome assembled de novo using PacBio sequence data. The PacBio RS data generated here were assembled into a single large contig spanning the P. micrantha chloroplast genome, with a higher degree of accuracy than an Illumina dataset generated at a much greater depth of coverage, due to longer read lengths and lower GC bias in the data. The results we present suggest PacBio data will be of immense utility for the development of genome sequence assemblies containing fewer unresolved gaps and ambiguities and a significantly smaller number of contigs than could be produced using short-read sequence data alone.
Functional analysis of the omega-6 fatty acid desaturase (CaFAD2) gene family of the oil seed crop Crambe abyssinica
Authors: Cheng Jihua , Zhu Li-Hua , Salentijn Elma MJ , Huang Bangquan , Gruber Jens , Dechesne Annemarie C , Krens Frans A , Qi Weicong , Visser Richard GF , van Loo Eibertus N
Published: October 2013

Background

Crambe abyssinica produces high erucic acid (C22:1, 55-60%) in the seed oil, which can be further increased by reduction of polyunsaturated fatty acid (PUFA) levels. The omega-6 fatty acid desaturase enzyme (FAD2) is known to be involved in PUFA biosynthesis. In crambe, three CaFAD2 genes, CaFAD2-C1, CaFAD2-C2 and CaFAD2-C3 are expressed.

Results

The individual effect of each CaFAD2 gene on oil composition was investigated through studying transgenic lines (CaFAD2-RNAi) for differential expression levels in relation to the composition of seed-oil. Six first generation transgenic plants (T1) showed C18:1 increase (by 6% to 10.5%) and PUFA reduction (by 8.6% to 10.2%). The silencing effect in these T1-plants ranged from the moderate silencing (40% to 50% reduction) of all three CaFAD2 genes to strong silencing (95% reduction) of CaFAD2-C3 alone. The progeny of two T1-plants (WG4-4 and WG19-6) was further analysed. Four or five transgene insertions are characterized in the progeny (T2) of WG19-6 in contrast to a single insertion in the T2 progeny of WG4-4. For the individual T2-plants of both families (WG19-6 and WG4-4), seed-specific silencing of CaFAD2-C1 and CaFAD2-C2 was observed in several individual T2-plants but, on average in both families, the level of silencing of these genes was not significant. A significant reduction in expression level (P < 0.01) in both families was only observed for CaFAD2-C3 together with significantly different C18:1 and PUFA levels in oil.

Conclusions

CaFAD2-C3 expression is highly correlated to levels of C18:1 (r = -0.78) and PUFA (r = 0.75), which suggests that CaFAD2-C3 is the most important one for changing the oil composition of crambe.
Exploration of experiences in therapeutic groups for patients with severe mental illness: development of the Ferrara group experiences scale (FE- GES)
Authors: Caruso Rosangela , Grassi Luigi , Biancosino Bruno , Marmai Luciana , Bonatti Luciano , Moscara Maria , Rigatelli Marco , Carr Catherine , Priebe Stefan
Published: October 2013

Background

Group therapies are routinely provided for patients with severe mental illness. The factors important to the group experience of patients are still poorly understood and are rarely measured. To support further research and practice, we aimed to develop a questionnaire that captures how patients experience groups within a community mental health context.

Methods

An initial pool of 39 items was conceptually generated to assess different aspects of group experiences. Items were completed by 166 patients with severe mental illness attending group therapies in community mental health services in Italy. Patients with different psychiatric diagnoses who attended at least 5 group sessions were included. An exploratory factor analysis was used to identify different dimensions of group experiences and to reduce the number of items for each dimension.

Results

The resulting questionnaire has five subscales: 1) sharing of emotions and experiences, 2) cognitive improvement, 3) group learning, 4) difficulties in open expression and 5) relationships. Each subscale has 4 items. The scale and sub-scales have good internal consistency.

Conclusions

The Ferrara Group Experiences Scale is conceptually derived and assesses dimensions of group experience that are theoretically and practically relevant. It is brief, easy to use and has good psychometric properties. After further validation, the scale may be used for research into patient experiences across different group therapy modalities and for evaluation in routine care.
Growth-Inhibiting and morphostructural effects of constituents identified in Asarum heterotropoides root on human intestinal bacteria
Authors: Perumalsamy Haribalan , Jung Moon Young , Hong Seung Min , Ahn Young-Joon
Published: October 2013

Background

The growth-inhibiting and morphostructural effects of seven constituents identified in Asarum heterotropoides root on 14 intestinal bacteria were compared with those of the fluoroquinolone antibiotic ciprofloxacin.

Method

A microtiter plate-based bioassay in sterile 96-well plates was used to evaluate the minimal inhibitory concentrations (MICs) of the test materials against the organisms.

Results

δ-3-Carene (5) exhibited the most potent growth inhibition of Gram-positive bacteria (Clostridium difficile ATCC 9689, Clostridium paraputrificum ATCC 25780, Clostridium perfringens ATCC 13124, and Staphylococcus aureus ATCC 12600) and Gram-negative bacteria (Escherichia coli ATCC 11775 and Bacteroides fragilis ATCC 25285) (minimal inhibitory concentrations (MIC), 0.18–0.70 mg/mL) except for Salmonella enterica serovar Typhimurium ATCC 13311 (MIC, 2.94 mg/mL). The MIC of methyleugenol (2), 1,8-cineole (3), α-asarone (4), (−)-asarinin (6), and pellitorine (7) was between 1.47 and 2.94 mg/mL against all test bacteria (except for compound 2 against C. difficile (0.70 mg/mL); compounds 1 (23.50 mg/mL) and 4 (5.80 mg/mL) against C. paraputricum; compounds 2 (5.80 mg/mL), 4 (12.0 mg/mL), and 7 (0.70 mg/mL) against C. perfringens); compound 1 against E. coli (7.20 mg/mL) and S. enterica serovar Typhimurium (12.0 mg/mL). Overall, all of the constituents were less potent at inhibiting microbial growth than ciprofloxacin (MIC, 0.063–0.25 mg/ mL). The lactic acid-producing bacteria (four bifidobacteria and two lactobacilli) and one acidulating bacterium Clostridium butyricum ATCC 25779 were less sensitive and more susceptible than the five harmful bacteria and two nonpathogenic bacteria (B. fragilis and E. coli) to the constituents and to ciprofloxacin, respectively. Beneficial Gram-positive bacteria and harmful and nonpathogenic Gram-negative bacteria were observed to have different degrees of antimicrobial susceptibility to the constituents, although the antimicrobial susceptibility of the harmful Gram-positive bacteria and the harmful and nonpathogenic Gram-negative bacteria was not observed. Scanning electron microscopy observations showed different degrees of physical damage and morphological alteration to both Gram-positive and Gram-negative bacteria treated with α-asarone, δ-3-carene, pellitorine, or ciprofloxacin, indicating that they do not share a common mode of action.

Conclusion

A. heterotropoides root-derived materials described merit further study as potential antibacterial products or lead molecules for the prevention or eradication from humans from diseases caused by harmful intestinal bacteria.
VRK2 identifies a subgroup of primary high-grade astrocytomas with a better prognosis
Authors: Rodríguez-Hernández Irene , Vázquez-Cedeira Marta , Santos-Briz Angel , García Juan L , Fernández Isabel F , Gómez-Moreta Juan A , Martin-Vallejo Javier , González-Sarmiento Rogelio , Lazo Pedro A
Published: October 2013

Background

Malignant astrocytomas are the most common primary brain tumors and one of the most lethal among human cancers despite optimal treatment. Therefore, the characterization of molecular alterations underlying the aggressive behavior of these tumors and the identification of new markers are thus an important step towards a better patient stratification and management.

Methods and results

VRK1 and VRK2 (Vaccinia-related kinase-1, -2) expression, as well as proliferation markers, were determined in a tissue microarray containing 105 primary astrocytoma biopsies. Kaplan Meier and Cox models were used to find clinical and/or molecular parameters related to overall survival. The effects of VRK protein levels on proliferation were determined in astrocytoma cell lines. High levels of both protein kinases, VRK1 or VRK2, correlated with proliferation markers, p63 or ki67. There was no correlation with p53, reflecting the disruption of the VRK-p53-DRAM autoregulatory loop as a consequence of p53 mutations. High VRK2 protein levels identified a subgroup of astrocytomas that had a significant improvement in survival. The potential effect of VRK2 was studied by analyzing the growth characteristics of astrocytoma cell lines with different EGFR/VRK2 protein ratios.

Conclusion

High levels of VRK2 resulted in a lower growth rate suggesting these cells are more indolent. In high-grade astrocytomas, VRK2 expression constitutes a good prognostic marker for patient survival.
Quantitative proteomic analysis in HCV-induced HCC reveals sets of proteins with potential significance for racial disparity
Authors: Dillon Simon T , Bhasin Manoj K , Feng Xiaoxing , Koh David W , Daoud Sayed S
Published: October 2013

Background

The incidence and mortality of hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC) is higher in African Americans (AA) than other racial/ethnic groups in the U.S., but the reasons for this disparity are unknown. There is an urgent need for the discovery of novel molecular signatures for HCV disease progression to understand the underlying biological basis for this cancer rate disparity to improve the clinical outcome.

Methods

We performed differential proteomics with isobaric labeling tags for relative and absolute quantitation (iTRAQ) and MS/MS analysis to identify proteins differentially expressed in cirrhotic (CIR) and HCC as compared to normal tissues of Caucasian American (CA) patients. The raw data were analyzed using the ProteinPilot v3.0. Searches were performed against all known sequences populating the Swiss-Prot, Refseq, and TrEMBL databases. Quality control analyses were accomplished using pairwise correlation plots, boxplots, principal component analysis, and unsupervised hierarchical clustering. Supervised analysis was carried out to identify differentially expressed proteins. Candidates were validated in independent cohorts of CA and AA tissues by qRT-PCR or Western blotting.

Results

A total of 238 unique proteins were identified. Of those, around 15% were differentially expressed between normal, CIR & HCC groups. Target validation demonstrates racially distinct alteration in the expression of certain proteins. For example, the mRNA expression levels of transferrin (TF) were 2 and18-fold higher in CIR and HCC in AA as compared to CA. Similarly; the expression of Apolipoprotein A1 (APOA1) was 7-fold higher in HCC of AA. This increase was mirrored in the protein expression levels. Interestingly, the level of hepatocyte nuclear factor4α (HNF4α) protein was down regulated in AA, whereas repression of transcription is seen more in CA compared to AA. These data suggest that racial disparities in HCC could be a consequence of differential dysregulation of HNF4α transcriptional activity.

Conclusion

This study identifies novel molecular signatures in HCV-induced HCC using iTRAQ-based tissue proteomics. The proteins identified will further enhance a molecular explanation to the biochemical mechanism(s) that may play a role in HCC racial disparities.
Astragalus injection protects cerebral ischemic injury by inhibiting neuronal apoptosis and the expression of JNK3 after cerebral ischemia reperfusion in rats
Authors: Liu Guangyi , Song Jinming , Guo Yunliang , Wang Tingting , Zhou Zhen
Published: October 2013

Background

Astragalus is a widely used traditional Chinese medicine and has been proven beneficial for many aspects of human health. It is important to explore the neuroprotective effect and mechanism of astragalus injection in cerebral ischemia reperfusion injury.

Methods

The focal cerebral ischemic model with middle cerebral artery occlusion (MCAO) reperfusion was established by Longa’s method in healthy adult male Wistar rats, and treated by injecting intraperitoneally astragalus injection (3 ml/kg). The neurobehavioral function of rats was evaluated by Longa’s test. The cerebral blood flow (CBF) was measured by laser Doppler flowmetry and the cerebral infarct volume was calculated by tetrazolium chloride (TTC) stain. The shape and structure of neurons in parahippocampal area was observed by HE stain and the neuronal apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and flow cytometry. The expressions of c-jun N-terminal kinase 3 (JNK3) mRNA and protein were determined by RT-PCR and immunohistochemical assay and Western blotting respectively.

Results

After treatment with astragalus injection, the expressions of JNK3 mRNA and protein reduced significantly, the number of neuronal apoptosis minus, the cerebral infarct volume shrink, the neuronal shape-structure and animal neurobehavioral function improved significantly than those in model rats.

Conclusions

It is suggested that astragalus injection could inhibit neuronal apoptosis, reduce infarct volume and improve neurobehavioral function by down-regulating the expression of JNK3 gene after cerebral ischemia reperfusion injury in rats.
Clozapine antipsychotic polypharmacy: audit of use and patient monitoring
Authors: Wilson Sam , Hamilton Ross , Callender John , MacManus Angela , Howitt Sheila , Okpo Blessing
Published: October 2013

Aims and method

We audited prescribing within our area to ascertain how widespread the practice of antipsychotic polypharmacy using clozapine was, and whether it was being carried out within existing standards, including those of high-dose monitoring when required.

Results

Data on 169 patients were reviewed in year one, rising to 193 in year three. Around 30% of patients on clozapine received additional antipsychotic medication. A disturbingly low proportion of patients on clozapine whose antipsychotic polypharmacy brought them into the high-dose range were being monitored appropriately after three audit cycles (the proportion rose from 10% in cycle 1 to 28% in cycle 3). A wide range of additional antipsychotic medications was used.

Clinical implications

Clozapine antipsychotic polypharmacy was prevalent at just below a third of all patients in this review. Prescribers should be alert to the fact that clozapine antipsychotic polypharmacy can push patients into the high-dose range and ensure appropriate monitoring.
Insulin-Like Growth Factor-1 Receptor-Mediated Inhibition of A-type K+ Current Induces Sensory Neuronal Hyperexcitability Through the Phosphatidylinositol 3-Kinase and Extracellular Signal-Regulated Kinase 1/2 Pathways, Independently of Akt
Authors: Wang Hua , Qin Jianzhong , Gong Shan , Feng Bo , Zhang Yuan , Tao Jin
Published: October 2013

Although IGF-1 has been implicated in mediating hypersensitivity to pain, the underlying mechanisms remain unclear. We identified a novel functional of the IGF-1 receptor (IGF-1R) in regulating A-type K+ currents (IA) as well as membrane excitability in small trigeminal ganglion neurons. Our results showed that IGF-1 reversibly decreased IA, whereas the sustained delayed rectifier K+ current was unaffected. This IGF-1–induced IA decrease was associated with a hyperpolarizing shift in the voltage dependence of inactivation and was blocked by the IGF-1R antagonist PQ-401; an insulin receptor tyrosine kinase inhibitor had no such effect. An small interfering RNA targeting the IGF-1R, or pretreatment of neurons with specific phosphatidylinositol 3-kinase (PI3K) inhibitors abolished the IGF-1–induced IA decrease. Surprisingly, IGF-1–induced effects on IA were not regulated by Akt, a common downstream target of PI3K. The MAPK/ERK kinase inhibitor U0126, but not its inactive analog U0124, as well as the c-Raf-specific inhibitor GW5074, blocked the IGF-1–induced IA response. Analysis of phospho-ERK (p-ERK) showed that IGF-1 significantly activated ERK1/2 whereas p-JNK and p-p38 were unaffected. Moreover, the IGF-1–induced p-ERK1/2 increase was attenuated by PI3K and c-Raf inhibition, but not by Akt blockade. Functionally, we observed a significantly increased action potential firing rate induced by IGF-1; pretreatment with 4-aminopyridine abolished this effect. Taken together, our results indicate that IGF-1 attenuates IA through sequential activation of the PI3K- and c-Raf-dependent ERK1/2 signaling cascade. This occurred via the activation of IGF-1R and might contribute to neuronal hyperexcitability in small trigeminal ganglion neurons.
Gestational Diabetes and Type 2 Diabetes in Reproductive-Aged Women With Polycystic Ovary Syndrome
Authors: Joham A. E. , Ranasinha S. , Zoungas S. , Moran L. , Teede H. J.
Published: October 2013

Context:

Polycystic ovary syndrome (PCOS) affects 6%–21% of women. PCOS has been associated with an increased risk of dysglycemia including gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM).

Objective:

The objective of the study was to assess the prevalence of dysglycemia and the impact of obesity in young reproductive-aged women with and without PCOS in a community-based cohort.

Design:

This was a cross-sectional analysis of data from a large longitudinal study (the Australian Longitudinal Study on Women's Health).

Setting:

The setting for the study was the general community.

Participants:

Women were randomly selected from the national health insurance database. Standardized data collection occurred at five survey time points (years 1996, 2000, 2003, 2006, and 2009). Data from survey 4 (2006, n = 9145, 62% of original cohort aged 18–23 y) were examined for this study.

Main Outcome Measures:

Self-reported PCOS, GDM, and T2DM were measured.

Results:

In women aged 28–33 years, PCOS prevalence was 5.8% [95% confidence interval (CI) 5.3%–6.4%]. The prevalence of GDM (in women reporting prior pregnancy) and T2DM was 11.2% and 5.1% in women with PCOS and 3.8% and 0.3% in women without PCOS, respectively (P for both < .001). PCOS was associated with an increased odds of GDM and T2DM. After adjusting for age, body mass index, hypertension, smoking, and demographic factors, the odds of GDM (odds ratio 2.1, 95% CI 1.1–3.9, P = .02) and T2DM (odds ratio 8.8, 95% CI 3.9–20.1, P < .001) remained increased in women reporting PCOS.

Conclusions:

In a large community-based cohort of reproductive-aged women, PCOS was independently associated with a higher risk of GDM and T2DM, independent of body mass index. Aggressive screening, prevention, and management of dysglycemia is clearly warranted in women with PCOS.
Update in Adrenocortical Carcinoma
Authors: Fassnacht Martin , Kroiss Matthias , Allolio Bruno
Published: October 2013

Adrenocortical carcinoma (ACC) is an orphan malignancy that has attracted increasing attention during the last decade. Here we provide an update on advances in the field since our last review published in this journal in 2006.

The Wnt/β-catenin pathway and IGF-2 signaling have been confirmed as frequently altered signaling pathways in ACC, but recent data suggest that they are probably not sufficient for malignant transformation. Thus, major players in the pathogenesis are still unknown.

For diagnostic workup, comprehensive hormonal assessment and detailed imaging are required because in most ACCs, evidence for autonomous steroid secretion can be found and computed tomography or magnetic resonance imaging (if necessary, combined with functional imaging) can differentiate benign from malignant adrenocortical tumors. Surgery is potentially curative in localized tumors. Thus, we recommend a complete resection including lymphadenectomy by an expert surgeon. The pathology report should demonstrate the adrenocortical origin of the lesion (eg, by steroidogenic factor 1 staining) and provide Weiss score, resection status, and quantitation of the proliferation marker Ki67 to guide further treatment. Even after complete surgery, recurrence is frequent and adjuvant mitotane treatment improves outcome, but uncertainty exists as to whether all patients benefit from this therapy.

In advanced ACC, mitotane is still the standard of care. Based on the FIRM-ACT trial, mitotane plus etoposide, doxorubicin, and cisplatin is now the established first-line cytotoxic therapy. However, most patients will experience progress and require salvage therapies. Thus, new treatment concepts are urgently needed. The ongoing international efforts including comprehensive “-omic approaches” and next-generation sequencing will improve our understanding of the pathogenesis and hopefully lead to better therapies.
Potential of Using a Nozzle at the Compressor Inlet of a High-Speed Direct-Injection Diesel Engine
Authors: Desantes J M , Luján J M , Plá B , Soler J A
Published: October 2013

The present work reports the effect of a nozzle placed upstream of the compressor of a high-speed direct-injection diesel engine. It has been observed that mounting a nozzle at the compressor inlet can lead to a shift in the compressor surge line to lower mass flowrates. In order to study the effect of the nozzle on the engine performance a set of experimental investigations has been conducted including characterization of the nozzle alone using a flow test rig up to sonic conditions and characterization of the nozzle—compressor unit by determining its operation map in a turbocharger test bench. The distortions in the compressor inlet are usually considered as a disadvantage, as they affect the efficiency and the behaviour of the turbocharger. However, the comparison between the original compressor map (provided by the manufacturer) and the nozzle—compressor map given in the present paper shows that the change in the flow pattern caused by the nozzle improves the engine—turbocharger coupling and thus reduces the air mass flowrate, leading to a surge by 30 per cent, for a given pressure ratio.

The improvement in turbocharging does not necessarily increase the performance of the engine. Nevertheless, the possibility of increasing the boost pressure allows elevated fuel flowrates to be applied while still maintaining the combustion efficiency, thus increasing the power of the engine
Systems Approach to the Improvement of Engine Warm-Up Behaviour
Authors: Burke R , Brace C , Cox A , Lewis A , Hawley J G , Pegg I , Stark R
Published: October 2013

Modifications to the coolant and oil circuits of a modern production 2.4 l diesel engine have been made in an attempt to promote oil warm-up to reduce fuel consumption. The new system used oil to cool exhaust gas recirculation (EGR) gases and incorporates a number of coolant flow control valves to reduce heat loss during warm-up. The engine was run over cold-start New European Drive Cycles with various flow strategies as a screening exercise to understand the behaviour of the system. Fuel consumption benefits of up to 4 per cent were observed, but these were accompanied by 3 per cent increases in nitrogen oxide (NO x) emissions. Detailed analysis of the coolant flows and temperatures showed that, when throttling the flow, the mass of coolant in the degas bottle and radiator could be isolated from the system during warm-up, essentially reducing the thermal inertia. Heat transfer directly to the oil from the EGR gases rather than via the coolant allowed more heat to be put into the oil, with engine oil supply temperatures up to 6 °C hotter; however, it was not possible to verify that the oil was hotter at the bearings, valve train, and cylinder liner. The engine strategy was seen to react to the faster warm-up and to retard injection timing, reducing NO x but also compromising overall fuel consumption benefits. Further tests were conducted with various injection timings to establish a NO x—fuel consumption trade-off to demonstrate further benefits when the engine strategy is included in the operation of novel thermal management systems.
Lattices and Lotteries
Authors: Antoniadou Elena , Mirman Leonard J , Ruble Richard
Published: October 2013

We consider the consumer problem under uncertainty when the consumer can choose the quantity of a risk-free good and the lottery, or distribution, of a risky good from a set of distributions. These goods are imperfect substitutes in the consumer preferences, with additive preferences a special case. We develop sufficient conditions for the choice of the risky good to be monotone with respect to income, exploring different notions of monotonicity. The sufficient conditions are ordinal, independent of concavity, and do not require differentiability or continuity. Cardinal conditions and conditions from the single good case are not necessary and are not always sufficient. The sufficient conditions are formulated in appropriate value lattices. The framework is flexible and adaptable to handle different uncertainty applications. Examples demonstrate the sufficient conditions and different applications where available lotteries may be finite in number, may have discrete support, or may form a chain or a lattice.
Fluid Limits for Bandwidth-Sharing Networks in Overload
Authors: Borst Sem , Egorova Regina , Zwart Bert
Published: October 2013

Bandwidth-sharing networks as considered by Roberts and Massoulié [28] (Roberts JW, Massoulié L (1998) Bandwidth sharing and admission control for elastic traffic. Proc. ITC Specialist Seminar, Yokohama, Japan) provide a natural modeling framework for describing the dynamic flow-level interaction among elastic data transfers. Under mild assumptions, it has been established that a wide family of so-called α-fair bandwidth-sharing strategies achieve stability in such networks provided that no individual link is overloaded.

In the present paper we focus on bandwidth-sharing networks where the load on one or several of the links exceeds the capacity. To characterize the overload behavior, we examine the fluid limit, which emerges when the flow dynamics are scaled in both space and time. We derive a functional equation characterizing the fluid limit, and show that any strictly positive solution must be unique, which in particular implies the convergence of the scaled number of flows to the fluid limit for nonzero initial states when the load is sufficiently high. For the case of a zero initial state and a zero-degree homogeneous rate allocation function, we show that there exists a linear solution to the fluid-limit equation, and obtain a fixed-point equation for the corresponding asymptotic growth rates. It is proved that a fixed-point solution is also a solution to a related strictly concave optimization problem, and hence exists and is unique. In addition, we establish uniqueness of fluid-model solutions for monotone rate-preserving networks (in particular tree networks).
Concave Generalized Flows with Applications to Market Equilibria
Authors: Végh László A.
Published: October 2013

We consider a nonlinear extension of the generalized network flow model, with the flow leaving an arc being an increasing concave function of the flow entering it, as proposed by Truemper [Truemper K (1978) Optimal flows in nonlinear gain networks. Networks 8(1):17–36] and by Shigeno [Shigeno M (2006) Maximum network flows with concave gains. Math. Programming 107(3):439–459]. We give a polynomial time combinatorial algorithm for solving corresponding flow maximization problems, finding an ε-approximate solution in O(m(mσ+log n)log(MUm/ε)) arithmetic operations, where M and U are upper bounds on simple parameters, and σ is the complexity of a value oracle query for the gain functions. This also gives a new algorithm for linear generalized flows, an efficient, purely scaling variant of the Fat-Path algorithm by Goldberg et al. [Goldberg AV, Plotkin SA, Tardos É (1991) Combinatorial algorithms for the generalized circulation problem. Math. Oper. Res. 16(2):351–381], not using any cycle cancellations.

We show that this general convex programming model serves as a common framework for several market equilibrium problems, including the linear Fisher market model and its various extensions. Our result immediately provides combinatorial algorithms for various extensions of these market models. This includes nonsymmetric Arrow-Debreu Nash bargaining, settling an open question by Vazirani [Vazirani VV (2012) The notion of a rational convex program, and an algorithm for the Arrow-Debreu Nash bargaining game. J. ACM 59(2), Article 7].
Experience In Creating The Uzbek Model Of Treasury
Authors: Kuchkarov Takhir
Published: October 2013

This article studies the issues of an information system of the Treasury in the post-Soviet countries. The advantages and disadvantages of centralized and decentralized forms of Treasury. Based on the analysis of creation and implementation of information system of the Treasury in Uzbekistan presented the findings and recommendations. This conclusions and suggestions can be used in designing and implementing information systems similar to the Treasury in other countries.
Sources Of Short-Term Finance And Investment Opportunaties
Authors: Yakhshibaev Gayrat
Published: October 2013

Global credit crunch makes difficult to obtain bank credits, for many small firms to find short-term finance resources getting the crucial issue. In such a situation  many firms delay their capital expenditures till indefinite time. Short-term investment opportunities appears most reliable direction to use cash surplus to maintain liquidity  during financial market volatility. This paper investigates the main directions of short term financing opportunities for small businesses and research’s the implementation methods of investment decision making. At the end author makes some conclusion the characteristics of new small business environment and gives his opinion about improvements of small businesses.
AUDIT OF FINANCIAL REPORTS, BASED ON INTERNATIONAL ACCOUNTING STANDARDS
Authors: Kuziev Islom
Published: October 2013

In this article are given main notion about international standard of financial reporting, order of the auditing on the base of IFRS, scheduling the report of the auditor, auditor conclusions and are given analysis of reporting based on the auditor procedures. At the audit of financial reporting are taken into account international standard to financial reporting 29 "Financial reporting in hyperinflationary economies".
The Mechanism Of The Functions Of Labor Market
Authors: Hudayberdiev Zafar
Published: October 2013

From theoretical point of view there are different approaches on determining the object that causes of buying -selling interactions in labor market. There are discussions since the middle of the last century. If the economists of CIS countries had the common view about it before the market economy, it became intricate under the influence of western economists.     From practical point of view, among the whole population of Uzbekistan the tendency of the growth of the population of working age and the shrink of dependency is observed, which requires to increase the number of employed among economic active population. It is important to mention that, during the financial- economic recession, the republic adopted anti-crisis program for 2009-2012, which mainly directed to the most important problems such as creating new labor places and improving the living standards of the population.
The Ways Of Increasing Competition In Social Services Sector
Authors: Kosimova Gulyor
Published: October 2013

The paper studies methods of calculation of competiveness of social service providers in Tashkent city  (Uzbekistan). Specific factors forming  economic­mathematical factors of competiveness of organizations (providers) of education, healthcare and cultural services are presented. As research shows all social services (public and commercial) of human capital development in Uzbekistan regulated by the same legislation  for  all  citizens  (in  some cases,  according legislation, these services are “free” for particular consumers). The main mechanism of increasing competiveness of organization is integration to public­private partnerships the research proved. The author suggests this partnership also is effective mechanism to improve competiveness.
CONTINUUM OF INSTITUTIONS OF STATE REGULATION AND SELF­REGULATION OF BUSINESS ORGANIZATIONS
Authors: Kovalenko Boris
Published: October 2013

Government regulation of business is based on the application of different rules of behavior of economic agents. These rules are being developed and implemented at the national and regional levels of economic regulation. At a certain stage of development of national and regional regulations are beginning to constrain the global interaction of the agents of economic development. This trend for the economy of Russia and many countries that have more attention udlyat create market conditions for farming. In order to further the economic development of space postsovetsvkogo gaining positive momentum necessary to reduce control over the actions of economic agents and to create a culture of self-regulation. We see the problem is to establish a balance of government regulation and self-regulation in a single continuum. To this end, studies were carried out the forms and methods of state regulation in the Russian economy, the advantages and disadvantages of self-regulation, self-regulatory organizations proposed classification, formulated the conditions under which self-regulation in the post-may be more effective form of impact on the behavior of economic agents than government regulation. In the article the author offers direction of public-private partnership: financial, logistical and administrative real. The development of public-private partnerships as a mechanism for interaction study of global parties “society - the state – business” in the management of priority areas of the economy.