bluuebunny/crossref_metadata_2025 huggingface dataset:
Terahertz-field-induced second-harmonic generation in a beta barium borate crystal and its application in terahertz detection
Authors: Chen Jian , Han Pengyu , Zhang X.-C.
Published: July 2009

We report the observation of terahertz-field-induced second-harmonic (TFISH) generation in a beta barium borate (β-BBO) crystal based on a four-wave-mixing process. Using the conventional second-harmonic generation in the β-BBO crystal as a local oscillator, the crossed term between the TFISH and the local oscillator is proportional to the terahertz field. This phenomenon is used for coherent detection of intense terahertz waves, where a good linear response is observed for terahertz fields up to 160 kV/cm. In comparison, deviation from linear response and strong waveform distortion are observed when a 0.5-mm-thick ZnTe detector is used to characterize the same terahertz field.
Surface reactions during atomic layer deposition of Pt derived from gas phase infrared spectroscopy
Authors: Kessels W. M. M. , Knoops H. C. M. , Dielissen S. A. F. , Mackus A. J. M. , van de Sanden M. C. M.
Published: July 2009

Infrared spectroscopy was used to obtain absolute number information on the reaction products during atomic layer deposition of Pt from (methylcyclopentadienyl)trimethylplatinum [(MeCp)PtMe3] and O2. From the detection of CO2 and H2O it was established that the precursor ligands are oxidatively decomposed during the O2 pulse mainly. Oxygen atoms chemisorbed at the Pt lead to likewise ligand oxidation during the (MeCp)PtMe3 pulse however the detection of a virtually equivalent density of CO2 and CH4 also reveals a concurrent ligand liberation reaction. The surface coverage of chemisorbed oxygen atoms found is consistent with the saturation coverage reported in surface science studies.
Simulated and experimental compression of a compact toroid
Authors: Johnson J. N. , Hwang D. Q. , Horton R. D. , Evans R. W. , Owen J. M.
Published: July 2009

We present simulation results and experimental data for the compression of a compact toroid by a conducting nozzle without a center electrode. In both simulation and experiment, the plasma flow is obstructed by even modest magnetic fields. A simple mechanism for this obstruction is suggested by our simulations. The configuration of the plasmoid’s magnetic field plays a significant role in its compression. We analyze two types of plasma configurations under compression and demonstrate that the results from the simulations match those from the experiments, and that the mechanism predicts the different behaviors observed in the two cases.
Financial Sophistication, Salience, and the Scale of Deliberation in UK Retirement Planning
Authors: Clark Gordon L , Knox-Hayes Janelle , Strauss Kendra
Published: July 2009

Whether people appreciate the importance of saving for the future, and whether they intend to do so, are not well understood. On the basis of a representative sample of UK residents, we show that the perceived importance of pension planning is positively correlated with respondents' risk tolerance, age, and income, and whether their spouses participate in employer-sponsored pension plans. Those less likely to believe planning for the future is important are younger, earn less, are women, and will rely upon others for their expected retirement welfare. It is also apparent that generic sources of information provided remotely or at the national scale for individual and household pension planning, preparedness, and knowledge of annuities do not stand comparison with the perceived value of intimate and specialist advisory relationships. The unit of retirement planning is typically the household; it rarely functions at the region and national scales. To understand these findings better we frame their interpretation with reference to recent behavioural research that emphasises people's limited cognitive and social resources and the use of heuristics such as salience in setting priorities. Our findings have important implications for the scope and significance of the relational turn in economic geography.
Distortions of Posterior Visual Space
Authors: Phillips Flip , Voshell Martin G
Published: July 2009

The study of spatial vision is a long and well traveled road (which, of course, converges to a vanishing point at the horizon). Its various distortions have been widely investigated empirically, and most concentrate, pragmatically, on the space anterior to the observer. The visual world behind the observer has received relatively less attention and it is this perspective the current experiments address. Our results show systematic perceptual distortions in the posterior visual world when viewed statically. Under static viewing conditions, observer's perceptual representation was consistently ‘spread’ in a hyperbolic fashion. Directions to distant, peripheral locations were consistently overestimated by about 11° from the ground truth and this variability increased as the target was moved toward the center of the observer's back. The perceptual representation of posterior visual space is, no doubt, secondary to the more immediate needs of the anterior visual world. Still, it is important in some domains including certain sports, such as rowing, and in vehicular navigation.
Automated multidimensional phenotypic profiling using large public microarray repositories
Authors: Xu Min , Li Wenyuan , James Gareth M. , Mehan Michael R. , Zhou Xianghong Jasmine
Published: July 2009

Phenotypes are complex, and difficult to quantify in a high-throughput fashion. The lack of comprehensive phenotype data can prevent or distort genotype–phenotype mapping. Here, we describe “PhenoProfiler,” a computational method that enables in silico phenotype profiling. Drawing on the principle that similar gene expression patterns are likely to be associated with similar phenotype patterns, PhenoProfiler supplements the missing quantitative phenotype information for a given microarray dataset based on other well-characterized microarray datasets. We applied our method to 587 human microarray datasets covering >14,000 samples, and confirmed that the predicted phenotype profiles are highly consistent with true phenotype descriptions. PhenoProfiler offers several unique capabilities: (
i
) automated, multidimensional phenotype profiling, facilitating the analysis and treatment design of complex diseases; (
ii
) the extrapolation of phenotype profiles beyond provided classes; and (
iii
) the detection of confounding phenotype factors that could otherwise bias biological inferences. Finally, because no direct comparisons are made between gene expression values from different datasets, the method can use the entire body of cross-platform microarray data. This work has produced a compendium of phenotype profiles for the National Center for Biotechnology Information GEO datasets, which can facilitate an unbiased understanding of the transcriptome-phenome mapping. The continued accumulation of microarray data will further increase the power of PhenoProfiler, by increasing the variety and the quality of phenotypes to be profiled.
Structure of the core editing complex (L-complex) involved in uridine insertion/deletion RNA editing in trypanosomatid mitochondria
Authors: Li Feng , Ge Peng , Hui Wong H. , Atanasov Ivo , Rogers Kestrel , Guo Qiang , Osato Daren , Falick Arnold M. , Zhou Z. Hong , Simpson Larry
Published: July 2009

Uridine insertion/deletion RNA editing is a unique form of posttranscriptional RNA processing that occurs in mitochondria of kinetoplastid protists. We have carried out 3D structural analyses of the core editing complex or “L (ligase)-complex” from
Leishmania tarentolae
mitochondria isolated by the tandem affinity purification procedure (TAP). The purified material, sedimented at 20–25S, migrated in a blue native gel at 1 MDa and exhibited both precleaved and full-cycle gRNA-mediated U-insertion and U-deletion in vitro activities. The purified L-complex was analyzed by electron tomography to determine the extent of heterogeneity. Three-dimensional structural comparisons of individual particles in the tomograms revealed that a majority of the complexes have a similar shape of a slender triangle. An independent single-particle reconstruction, using a featureless Gaussian ball as the initial model, converged to a similar triangular structure. Another single-particle reconstruction, using the averaged tomography structure as the initial model, yielded a similar structure. The REL1 ligase was localized on the model to the base of the apex by decoration with REL1-specific IgG. This structure should prove useful for a detailed analysis of the editing reaction.
Mitochondrial phosphoglycerate mutase 5 uses alternate catalytic activity as a protein serine/threonine phosphatase to activate ASK1
Authors: Takeda Kohsuke , Komuro Yoshiko , Hayakawa Teruyuki , Oguchi Haruka , Ishida Yosuke , Murakami Shiori , Noguchi Takuya , Kinoshita Hideyuki , Sekine Yusuke , Iemura Shun-ichiro , Natsume Tohru , Ichijo Hidenori
Published: July 2009

Phosphoglycerate mutase (PGAM) is an enzyme of intermediary metabolism that converts 3-phosphoglycerate to 2-phosphoglycerate in glycolysis. Here, we discovered PGAM5 that is anchored in the mitochondrial membrane lacks PGAM activity and instead associates with the MAP kinase kinase kinase ASK1 and acts as a specific protein Ser/Thr phosphatase that activates ASK1 by dephosphorylation of inhibitory sites. Mutation of an active site His-105 in PGAM5 abolished phosphatase activity with ASK1 and phospho-Thr peptides as substrates. The
Drosophila
and
Caenorhabditis elegans
orthologs of PGAM5 also exhibit specific Ser/Thr phosphatase activity and activate the corresponding
Drosophila
and
C. elegans
ASK1 kinases. PGAM5 is unrelated to the other known Ser/Thr phosphatases of the PPP, MPP, and FCP families, and our results suggest that this member of the PGAM family has crossed over from small molecules to protein substrates and been adapted to serve as a specialized activator of ASK1.
Vancomycin-Resistant Enterococci in Long-Term Care Facilities
Authors: Benenson Shmuel , Cohen Matan J. , Block Colin , Stern Sagit , Weiss Yuval , Moses Allon E. ,   JIRMI Group
Published: July 2009

Knowledge of the prevalence rates and associated risk markers of vancomycin-resistant enterococci (VRE) colonization among long-term care facility (LTCF) residents could be used to improve screening policies among newly admitted hospital inpatients. In a cross-sectional survey among 1,215 residents of LTCFs in Jerusalem, the VRE carriage rate was 9.6%. Previous hospitalization and antibiotic treatment were associated with elevated VRE colonization rate. In contrast, moderate and severe levels of dependency and prolonged stay, in an LTCF were associated with a decrease in the VRE colonization rate.
Dichelesthium oblongum (Copepoda: Dichelesthiidae) infestation in wild-caught Atlantic sturgeon, Acipenser oxyrinchus oxyrinchus
Authors: Fast Mark D. , Sokolowski Mark S. , Dunton Keith J. , Bowser Paul R.
Published: July 2009

Fast, M. D., Sokolowski, M. S., Dunton, K. J., and Bowser, P. R. 2009. Dichelesthium oblongum (Copepoda: Dichelesthiidae) infestation in wild-caught Atlantic sturgeon, Acipenser oxyrinchus oxyrinchus. – ICES Journal of Marine Science, 66: 2141–2147. Atlantic sturgeon were sampled in autumn 2007 and 2008 along the New York Bight. The fish were examined for the presence of external parasites, and blood, fin, and opercula biopsies were collected for subsequent serum analysis and histopathological evaluation. Dichelesthium oblongum, a parasitic copepod, was observed on 93% of the sturgeon sampled (77 out of 83) between Rockaway and Jones Beaches, NY, and Sandy Hook, NJ. During the course of the examinations, grossly visible lesions associated with the attachment and feeding of juvenile stages of D. oblongum were noted on the operculum, pectoral, dorsal, and anal fins of infested fish. Significant differences were observed between the level of infestation and serum chemistry across sampling sites, such that the most heavily infested fish were caught off Jones Beach (15.8 ± 2.79 lice fish−1), higher infestations than at Rockaway Beach (8.86 ± 0.89 lice fish−1) and Sandy Hook (5.31 ± 1.40 lice fish−1). Animals from Jones Beach also indicated ion loading (i.e. sodium, calcium, and magnesium), possibly as a result of stress or water loss through D. oblongum infestation compromising the epithelial barrier. The interaction of the environment and parasite with host life-history characteristics are discussed in terms of their ecological significance to this threatened fish species.
Virulence variation among isolates of western equine encephalitis virus in an outbred mouse model
Authors: Logue Christopher H. , Bosio Christopher F. , Welte Thomas , Keene Kimberley M. , Ledermann Jeremy P. , Phillips Aaron , Sheahan Brian J. , Pierro Dennis J. , Marlenee Nicole , Brault Aaron C. , Bosio Catharine M. , Singh Amber J. , Powers Ann M. , Olson Ken E.
Published: July 2009

Little is known about viral determinants of virulence associated with western equine encephalitis virus (WEEV). Here, we have analysed six North American WEEV isolates in an outbred CD1 mouse model. Full genome sequence analyses showed ≤2.7 % divergence among the six WEEV isolates. However, the percentage mortality and mean time to death (MTD) varied significantly when mice received subcutaneous injections of 103 p.f.u. of each virus. Two WEEV strains, McMillan (McM) and Imperial 181 (IMP), were the most divergent of the six in genome sequence; McM caused 100 % mortality by 5 days post-infection, whereas IMP caused no mortality. McM had significantly higher titres in the brain than IMP. Similar differences in virulence were observed when McM and IMP were administered by aerosol, intranasal or intravenous routes. McM was 100 % lethal with an MTD of 1.9 days when 103 p.f.u. of each virus was administered by intracerebral inoculation; in contrast, IMP caused no mortality. The presence of IMP in the brains after infection by different routes and the lack of observed mortality confirmed that IMP is neuroinvasive but not neurovirulent. Based on morbidity, mortality, MTD, severity of brain lesions, virus distribution patterns, routes of infection and differences in infection of cultured cells, McM and IMP were identified as high- and low-virulence isolates, respectively.
Proteasome inhibitors promote the sequestration of PrPSc into aggresomes within the cytosol of prion-infected CAD neuronal cells
Authors: Dron Michel , Dandoy-Dron Françoise , Farooq Salamat Muhammad Khalid , Laude Hubert
Published: July 2009

Dysfunction of the endoplasmic reticulum associated protein degradation/proteasome system is believed to contribute to the initiation or aggravation of neurodegenerative disorders associated with protein misfolding, and there is some evidence to suggest that proteasome dysfunctions might be implicated in prion disease. This study investigated the effect of proteasome inhibitors on the biogenesis of both the cellular (PrPC) and abnormal (PrPSc) forms of prion protein in CAD neuronal cells, a newly introduced prion cell system. In uninfected cells, proteasome impairment altered the intracellular distribution of PrPC, leading to a strong accumulation in the Golgi apparatus. Moreover, a detergent-insoluble and weakly protease-resistant PrP species of 26 kDa, termed PrP26K, accumulated in the cells, whether they were prion-infected or not. However, no evidence was found that, in infected cells, this PrP26K species converts into the highly proteinase K-resistant PrPSc. In the infected cultures, proteasome inhibition caused an increased intracellular aggregation of PrPSc that was deposited into large aggresomes. These findings strengthen the view that, in neuronal cells expressing wild-type PrPC from the natural promoter, proteasomal impairment may affect both the process of PrPC biosynthesis and the subcellular sites of PrPSc accumulation, despite the fact that these two effects could essentially be disconnected.
Oligonucleotide array analysis of Toll-like receptors and associated signalling genes in Venezuelan equine encephalitis virus-infected mouse brain
Authors: Sharma Anuj , Maheshwari Radha K.
Published: July 2009

Venezuelan equine encephalitis (VEE) is an emerging infectious disease. VEE virus (VEEV) may cause lethal infection of the central nervous system in horses and humans. The mechanisms underlying the host immune response to VEEV infection in the brain are not fully understood. Toll-like receptors (TLRs) recognize conserved microbial sequences and induce specific biological responses in the form of proinflammatory cytokine induction. TLR expression in blood following VEEV infection has been reported in non-human primates and TLRs are also upregulated in the brains of mice infected with other alphaviruses. In this study, mice (3–5 weeks old) were infected with V3000, a neurovirulent strain of VEEV, and gene expression of TLRs and their associated signalling molecules was evaluated. VEEV infection resulted in upregulation ofTLR 1,2,3,7and9, chemokines, inflammatory cytokines, interferon (IFN), IFN regulatory factors and genes involved in signal transduction such asMcp1,Cxcl10,IL12α/β,IFN-β,IRF-1,IRF-7,Jun,Fos,MyD88,Nfkb,Cd14andCd86. These results demonstrate the upregulation of TLRs and associated signalling genes following VEEV infection of the brain, with important implications for how VEEV induces inflammation and neurodegeneration.
Formulation of bovine respiratory syncytial virus fusion protein with CpG oligodeoxynucleotide, cationic host defence peptide and polyphosphazene enhances humoral and cellular responses and induces a protective type 1 immune response in mice
Authors: Kovacs-Nolan J. , Mapletoft J. W. , Lawman Z. , Babiuk L. A. , van Drunen Littel-van den Hurk S.
Published: July 2009

Respiratory syncytial virus (RSV) is the leading cause of serious respiratory tract disease in children and calves; however, RSV vaccine development has been slow due to early observations that formalin-inactivated vaccines induced Th2-type immune responses and led to disease enhancement upon subsequent exposure. Hence, there is a need for novel adjuvants that will promote a protective Th1-type or balanced immune response against RSV. CpG oligodeoxynucleotides (ODNs), indolicidin, and polyphosphazene were examined for their ability to enhance antigen-specific immune responses and influence the Th-bias when co-formulated with a recombinant truncated bovine RSV (BRSV) fusion protein (ΔF). Mice immunized with ΔF co-formulated with CpG ODN, indolicidin, and polyphosphazene (ΔF/CpG/indol/PP) developed higher levels of ΔF-specific serum IgG, IgG1 and IgG2a antibodies when compared with ΔF alone, and displayed an increase in the frequency of gamma interferon-secreting cells and decreased interleukin (IL)-5 production byin vitrorestimulated splenocytes, characteristic of a Th1 immune response. These results were observed in both C57BL/6 and BALB/c strains of mice. When evaluated in a BRSV challenge model, mice immunized with ΔF/CpG/indol/PP developed significantly higher levels of BRSV-neutralizing serum antibodies than mice immunized with the ΔF protein alone, and displayed significantly less pulmonary IL-4, IL-5, IL-13 and eotaxin and reduced eosinophilia after challenge. These results suggest that co-formulation of ΔF with CpG ODN, host defence peptide and polyphosphazene may result in a safe and effective vaccine for the prevention of BRSV and may have implications for the development of novel human RSV vaccines.
Cellular kinase inhibitors that suppress enterovirus replication have a conserved target in viral protein 3A similar to that of enviroxime
Authors: Arita Minetaro , Wakita Takaji , Shimizu Hiroyuki
Published: July 2009

Previously, we identified a cellular kinase inhibitor, GW5074, that inhibits poliovirus (PV) and enterovirus 71 replication strongly, although its target has remained unknown. To identify the target of GW5074, we searched for cellular kinase inhibitors that have anti-enterovirus activity similar or related to that of GW5074. With this aim, we performed screenings to identify cellular kinase inhibitors that could inhibit PV replication cooperatively with GW5074 or synthetically in the absence of GW5074. We identified MEK1/2 inhibitors (SL327 and U0126), an EGFR inhibitor (AG1478) and a phosphatidylinositol 3-kinase inhibitor (wortmannin) as compounds with a cooperative inhibitory effect with GW5074, and an Akt1/2 inhibitor (Akt inhibitor VIII) as a compound with a synthetic inhibitory effect with MEK1/2 inhibitors and AG1478. Individual treatment with the identified kinase inhibitors did not affect PV replication significantly, but combined treatment with MEK1/2 inhibitor, AG1478 and Akt1/2 inhibitor suppressed the replication synthetically. The effect of AG1478 in this synthetic inhibition was compensated by other receptor tyrosine kinase inhibitors (IGF-1R inhibitor II and Flt3 inhibitor II). We isolated mutants resistant to Flt3 inhibitor II and GW5074 and found that these mutants had cross-resistance to each treatment. These mutants had a common mutation in viral protein 3A that results in an amino acid change at position 70 (Ala to Thr), a mutation that was previously identified in mutants resistant to a potent anti-enterovirus compound, enviroxime. These results suggest that cellular kinase inhibitors and enviroxime have a conserved target in viral protein 3A to suppress enterovirus replication.
Diffraction-line shift caused by residual stress in polycrystal for all Laue groups in classical approximations
Authors: Popa N. C.
Published: July 2009

Analytical formulae for all Laue groups are derived, giving the dependence of the residual elastic strain measured by X-ray and neutron diffraction on the direction in the sample and on the Miller indices. These formulae are valid for isotropic polycrystals in the limits of the Reuss and Voigt approximations and are appropriate for Rietveld refinement.
Polymorphism in the spin-crossover ferric complexes [(TPA)FeIII(TCC)]PF6
Authors: Collet Eric , Boillot Marie-Laure , Hebert Johan , Moisan Nicolas , Servol Marina , Lorenc Maciej , Toupet Loïc , Buron-Le Cointe Marylise , Tissot Antoine , Sainton Joelle
Published: July 2009

We have identified two polymorphs of the molecular complex [(TPA)Fe(III)(TCC)]PF6 [TPA = tris(2-pyridylmethyl)amine and TCC = 3,4,5,6-tetrachlorocatecholate dianion]: one is monoclinic and the other is orthorhombic. By lowering the temperature both undergo a thermal spin-crossover between a high-spin (S = 5/2) and a low-spin (S = 1/2) state, which we detected by magnetic, optical and X-ray diffraction measurements. The thermal crossover is only slightly shifted between the polymorphs. Their crystalline structures consist of similar cation layers alternating with PF6 anion layers, packed differently in the two polymorphs. The magnetic and optical properties of the polymorphs are presented.
Biennial Budgeting by the U.S. Congress
Authors: Meyers Roy T.
Published: July 2009

Should the Congress prepare a budget every two years rather than every year, as it does now? This article condenses a recent Congressional Budget Office (CBO) working paper that analyzed this issue for the Congress. It describes the movement toward biennial budgeting in the federal government, summarizes state experiences with biennial budgeting, and evaluates biennial budgeting from the congressional perspective.
Coherence, correspondence, and the renaissance of morphology in phylogenetic systematics
Authors: Assis Leandro C. S.
Published: July 2009

The decline in morphological phylogenies has become a pronounced trend in contemporary systematics due to a disregard for theoretical, methodological, conceptual, and philosophical approaches. The role and meaning of morphology in phylogenetic reconstruction and classification have been undermined by the following: (i) the ambiguous delineation of morphological characters; (ii) the putative “objectivity” of molecular data; (iii) that morphology has not been included in data matrices; (iv) that morphology has been mapped onto molecular cladograms; and (v) a separation of a paradigmatic relationship among morphology, phylogeny, and classification. Historical/philosophical arguments including the synthesis of coherence (coherentism) and correspondence (foundationalism) theories—i.e. “foundherentism” as a theory of epistemic justification—provide support for a renaissance of morphology in phylogenetic systematics. In the language of systematics, coherence theory corresponds to the logical/operational congruence of character states translated into a hierarchical/relational system of homologues and monophyletic groups as natural kinds. Correspondence theory corresponds to the empirical/causal accommodation of homologues and monophyletic groups as natural kinds grounded in the concept of semaphoront, and in developmental biology, genetics, inheritance, ontogenesis, topology, and connectivity. The role and meaning of morphology are also discussed in the context of separate and combined analyses, palaeontology, natural kinds, character concepts, semaphoront, modularity, and taxonomy. Molecular systematics suffers from tension between coherence and correspondence theories, and fails to provide a pragmatic language for predicates in science and in everyday life. Finally, the renaissance of morphology is not only dependent on a scientific/philosophical perspective but also depends on political, economic, social, and educational reforms in contemporary systematics.

 © The Willi Hennig Society 2009.
Human epithelial ovarian carcinoma cell‐derived cytokines cooperatively induce activated CD4+CD25−CD45RA+ naïve T cells to express forkhead box protein 3 and exhibit suppressive ability in vitro
Authors: Zhao Xiaofeng , Ye Feng , Chen Lili , Lu Weiguo , Xie Xing
Published: July 2009

Regulatory T cells play an important role in tumor escape from host antitumor immunity. Increased frequencies of CD4+CD25+ regulatory T cells have been documented in the tumor sites, malignant effusions, and peripheral blood of patients with ovarian carcinoma. However, the mechanism involved remains unclear. In the present study, we collected high‐purity human CD4+CD25−CD45RA+ naïve T cells by microbead cell separation. These cells did not express FOXP3 by single‐cell analysis, and few cells expressed FOXP3 when they were activated with anti‐CD3/CD28 dual signal. However, more cells expressed FOXP3 when the supernatant of human epithelial ovarian carcinoma cell culture was added, yet not the supernatant of normal human ovarian surface epithelia cell culture. Neutralization assays revealed that neutralizing antibody against transforming growth factor β (TGF‐β), interleukin‐10, and interleukin‐4 did not abrogate elevated FOXP3 expression induced by carcinoma cell culture supernatant, whereas neutralizing leukemia inhibitory factor (LIF) partially abrogated FOXP3 expression, but LIF alone could not increase FOXP3 expression in activated naïve T cells. Further, an in vitro coculture suppression assay showed that these cells could suppress the proliferation of autologous CD4+CD25−CD45RA− T cells. In summary, our findings show that ovarian carcinoma cells are able to induce expression of FOXP3 and exhibit suppressive ability in activated naïve T cells by producing soluble substances, and multiple cytokines involve in the induction of FOXP3 expression. (Cancer Sci 2009)
Clinical trial: music reduces anxiety levels in patients attending for endoscopy
Authors: EL‐HASSAN H. , MCKEOWN K. , MULLER A. F.
Published: July 2009

Background  Patients attending for endoscopy are generally anxious and worried.

Aims  To examine whether music reduced anxiety levels in patients attending for endoscopic procedures.

Methods  Prospective randomized controlled trial of 180 patients (M:F 81:99). The effect of age (≤ or >51 years) and procedure (gastroscopy or flexible sigmoidoscopy/colonoscopy) on anxiety levels (state‐trait anxiety inventory) on arrival in the unit and immediately before the endoscopy procedure, after listening to music or no music (control group) for the same period.

Results  At baseline, anxiety levels were not influenced by age (≤51 years, n = 56:42.21 ± 9.18; >51 years, n = 124:39.99 ± 10.13 (P = 0.15) or procedure: gastroscopy, n = 87:39.43 ± 9.9, flexible sigmoidoscopy/colonoscopy: n = 93:41.86 ± 9.75 (P = 0.98). No difference was found in anxiety scores in the control group (n = 88) at baseline and immediately pre‐endoscopy (P = 0.243), but music led to a significant reduction in anxiety scores (n = 92), which was maintained for all age groups irrespective of procedure (all P < 0.0001).

Conclusions  Anxiety levels in patients attending for endoscopy were not influenced by age or procedure, but were significantly reduced by listening to music compared to controls. The availability of music within the endoscopy unit is a simple strategy that will improve the well‐being of patients.
Clinical trial: long‐term use of proton pump inhibitors in primary care patients – a cross sectional analysis of 901 patients
Authors: REIMER C. , BYTZER P.
Published: July 2009

Background  The use of proton pump inhibitors (PPIs) is extensive. While the incidence of new treatments remains stable, the prevalence of long‐term treatment is rising. Studies have shown that up to 70% of patients on chronic acid suppression lack a verified indication for treatment.

Aims  To investigate primary care patient characteristics associated with long‐term use of PPIs.

Methods  A cross‐sectional analysis of 42 634 patients registered with 22 general practitioners was performed. Patients with prescriptions of ≥120 tablets/year were defined as long‐term users. A survey of a subgroup of patients without verified indication was performed.

Results  In all, 901 (2.1%) patients were long‐term treated. Verified indications for treatment were identified for 247/901 (27%). An upper GI endoscopy had been performed in 418 patients (46%). Of the 194/654 without verified indication who participated in the survey, 71% reported heartburn/acid regurgitation as the reason for therapy. On‐demand therapy was reported by 43/194 (22%) and previous attempts to withdraw by 119/194 (61%).

Conclusions  The prevalence of PPI long‐term treatment among primary care patients is 2.1%. The main reason for treatment is reflux symptoms or verified GERD. Rationalization of use of PPIs is possible as daily treatment without attempts to discontinue is frequently observed.
Clinical pharmacy‐led disease and medicine management programme for patients with COPD
Authors: Khdour Maher R. , Kidney Joseph C. , Smyth Bronagh M. , McElnay James C.
Published: July 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The concept of self‐management plans for patients with chronic obstructive pulmonary disease (COPD) is derived from their success in asthma management.

• It is believed that selected people with COPD may benefit from the early intervention that comes from following self‐management plans, which may prevent a crisis and possibly the need for hospital admission.

• There is little published information on clinical pharmacist‐led disease and patient self‐management in the area of COPD care.

WHAT THIS STUDY ADDS

• A structured education programme led by a clinical pharmacist for patients with COPD was associated with a reduction in both hospitalization and emergency department visits and an improvement in patients' adherence to treatment regimens and health‐related quality of life (excluding physical activity).

• The intervention programme was tailored and individualized based on a preliminary assessment of individual patient needs.

• Education about self‐management in COPD patients should be explicit, tailored to individual needs, and on a continuous basis.

AIM

The aim was to investigate the impact of a disease and medicine management programme, focusing on self‐management in patients with chronic obstructive pulmonary disease (COPD).

METHODS

One hundred and seventy‐three patients (mean age 67 years; 54% female) were recruited; 86 patients were randomly assigned to an intervention group and 87 to a usual care (control) group. Intervention patients received education on disease state, medications and breathing techniques. Patients were given booklets and a customized action plan (antibiotic and oral steroid to be initiated promptly by patients for exacerbations). Patients were followed up at 6 and 12 months during a scheduled visit. The St George's Respiratory Questionnaire (SGRQ), COPD Knowledge and Morisky adherence questionnaires were administered to all patients at baseline, 6 and 12 months. Outcome measures included hospital admissions, emergency department (ED) visits, health‐related quality of life (HRQoL) and medication adherence.

RESULTS

Over the 12‐month period in the intervention group, ED visits decreased by 50% (P= 0.02) and hospitalization by approximately 60% (P= 0.01). On the SGRQ, differences reached statistical significance on the symptom (−7.5; P= 0.04) and impact (−7.4; P= 0.03) subscales but not on the physical activity subscale. There was a significant difference between the intervention and usual care groups regarding knowledge scores (75.0 vs. 59.3; P= 0.001) and good adherence to medication (77.8% vs. 60.0%, P= 0.019). There was no significant difference regarding smoking between study groups.

CONCLUSIONS

The clinical pharmacy‐led management programme can improve adherence, reduce the need for hospital care in patients with COPD and improve aspects of their HRQoL.
Structurally diverse peroxisome proliferator‐activated receptor agonists induce apoptosis in human uro‐epithelial cells by a receptor‐independent mechanism involving store‐operated calcium channels
Authors: Chopra B. , Georgopoulos N. T. , Nicholl A. , Hinley J. , Oleksiewicz M. B. , Southgate J. 
Published: July 2009

Objectives: Peroxisome proliferator‐activated receptors (PPARs) are implicated in epithelial cell proliferation and differentiation, but investigation has been confounded by potential off‐target effects of some synthetic PPAR ligands. Our aim was to determine mechanisms underlying the pro‐apoptotic effect of synthetic PPAR agonists in normal human bladder uro‐epithelial (urothelial) cells and to reconcile this with the role of PPARs in urothelial cytodifferentiation.

Materials and methods: Normal human urothelial (NHU) cells were grown as non‐immortal linesin vitroand exposed to structurally diverse agonists ciglitazone, troglitazone, rosiglitazone (PPARγ), ragaglitazar (PPARα/γ), fenofibrate (PPARα) and L165041 (PPARβ/δ).

Results: NHU cells underwent apoptosis following acute exposure to ciglitazone, troglitazone or ragaglitazar, but not fenofibrate, L165041 or rosiglitazone, and this was independent of ERK or p38 MAP‐kinase activation. Pro‐apoptotic agonists induced sustained increases in intracellular calcium, whereas removal of extracellular calcium altered the kinetics of ciglitazone‐mediated calcium release from sustained to transient. Cell death was accompanied by plasma‐membrane disruption, loss of mitochondrial membrane‐potential and caspase‐9/caspase‐3 activation. PPARγ‐mediated apoptosis was unaffected following pre‐treatment with PPARγ antagonist T0070907 and was strongly attenuated by store‐operated calcium channel (SOC) inhibitors 2‐APB and SKF‐96365.

Conclusions: Our results provide a mechanistic basis for the ability of some PPAR agonists to induce death in NHU cells and demonstrate that apoptosis is mediatedviaPPAR‐independent mechanisms, involving intracellular calcium changes, activation of SOCs and induction of the mitochondrial apoptotic pathway.
Missing siblings: seeking more adequate social responses
Authors: Clark Julie , Warburton Jeni , Tilse Cheryl
Published: July 2009

Little is known about the experience of family and friends when a young adult goes missing, less is known about how siblings make sense of the experience. Police assistance to locate the missing person may be sought but there is little recognition of going missing or missingness as a social issue, and there is little or no adequate social response to the needs of those left behind. This paper links knowledge of siblings, loss and grief to an understanding of this phenomenon. It presents the methodology and findings of an exploratory, qualitative study into the experiences of nine adult siblings of long‐term missing people in Australia and presents the themes drawn from their accounts. The themes are briefly elaborated using direct quotations from participants in the study and represented in a diagram. The paper seeks to develop greater understanding of the inter‐relationship between missingness and other social issues, to give voice to the views of participants and to encourage practitioners to engage more purposefully in work with family and friends affected by this issue. Some implications for social work practice are presented.
Broken circles to a different identity: an exploration of identity for children in out–of‐home care in Queensland, Australia
Authors: Moss Michelle
Published: July 2009

Child protection manuals and literature emphasize that developing a sense of identity is one of the most important elements in achieving good outcomes for children in out‐of‐home care. Yet, the very issue of identity raises questions that many child protection workers are ill‐equipped to answer. In practice, life story book work based on developmental theories has been utilized by child protection workers and foster carers as a response to a sense of ‘lost identity’ for children in out‐of‐home care. However, Indigenous and psychological concepts of identity may have little in common.

Current theories of identity development in children lack evidence from the children and young people themselves in informing these notions, which have been criticized as adult‐centric. Developmental theories may also be problematic for children from non‐Western cultural groups. This research was undertaken in a regional area of Queensland, Australia where the majority of children in the child protection system who are identified as Indigenous, come from two or more cultural backgrounds. The research presented in this paper firstly explores identity issues for children and young people in foster care from their own perspective using narrative art therapy. Secondly, the research views identity from the perspective of professionals working in child protection and out‐of‐home care.
Bangladeshi families living in hardship: findings from research using a life‐history approach
Authors: Dyson Claire , Gorin Sarah , Hooper Carol‐Ann , Cabral Christie
Published: July 2009

Whilst there are many commonalities in the experience of living in hardship, there are also many ways in which the experience of poverty varies. This paper draws on findings from life‐history interviews about parenting and children's well‐being which were undertaken with 70 low‐income households including nine Bangladeshi families living in London. The paper explores the ways in which the experience of Bangladeshi families was similar to and different from the sample as a whole, discusses the intersection of culture, class, gender and ethnicity in the experience of living in poverty and how this impacted on parents' ability to access support. The findings show the many and complex ways poverty impacts on families' lives and suggest that many of the barriers for Bangladeshi families' to accessing services that have previously been identified still exist. The findings highlight the importance of social workers having the space to reflect on and develop their own practice in order to avoid oversimplistic assumptions about the experiences of Bangladeshi families and the need for home‐visiting services so practitioners can develop relationships and build the confidence of the most socially excluded parents.
Monthly recombinant tissue plasminogen activator administration to implantable central venous access devices decreases infections in children with haemophilia
Authors: JENG M. R. , O’BRIEN M. , WONG W. , ZOLAND J. , LEA J. , TANG N. , GLADER B.
Published: July 2009

Summary.  Central venous access devices (CVAD) have been effectively used in the care of haemophilia patients. This is particularly true in children, who often have difficult venous access. CVAD complications (infection and thrombosis), risk factors, and complication rates, have been well‐documented. However, effective interventions which decrease complication rates have not been identified. In this study, we review our experience with the use of monthly recombinant tissue plasminogen activator (rtPA) administration in haemophilia patients with fully implanted CVADs. Data on 19 haemophilia patients with 24 CVADs were available for analysis, with a total of 24 520 CVAD days. An infection rate of 0.04 infections per 1000 CVAD days and a thrombosis rate of 0.04 thrombi per 1000 CVAD days was observed. The observed infectious complication rate is at least one logarithm lower than many published CVAD infection rates in haemophilia patients who have not received rtPA administration. No bleeding complications were noted. Monthly rtPA is safe and appears to be effective in decreasing CVAD infection rates. Larger, randomized controlled studies are indicated to validate this finding.
Using a minigene approach to characterize a novel splice site mutation in human F7 gene causing inherited factor VII deficiency in a Chinese pedigree
Authors: YU T. , WANG X. , DING Q. , FU Q. , DAI J. , LU Y. , XI X. , WANG H.
Published: July 2009

Summary.  Factor VII deficiency which transmitted as an autosomal recessive disorder is a rare haemorrhagic condition. The aim of this study was to identify the molecular genetic defect and determine its functional consequences in a Chinese pedigree with FVII deficiency. The proband was diagnosed as inherited coagulation FVII deficiency by reduced plasma levels of FVII activity (4.4%) and antigen (38.5%). All nine exons and their flanking sequence of F7 gene were amplified by polymerase chain reaction (PCR) for the proband and the PCR products were directly sequenced. The compound heterozygous mutations of F7 (NM_000131.3) c.572‐1G>A and F7 (NM_000131.3) c.1165T>G; p.Cys389Gly were identified in the proband’s F7 gene. To investigate the splicing patterns associated with F7 c.572‐1G>A, ectopic transcripts in leucocytes of the proband were analyzed. F7 minigenes, spanning from intron 4 to intron 7 and carrying either an A or a G at position ‐1 of intron 5, were constructed and transiently transfected into human embryonic kidney (HEK) 293T cells, followed by RT‐PCR analysis. The aberrant transcripts from the F7 c.572‐1G>A mutant allele were not detected by ectopic transcription study. Sequencing of the RT‐PCR products from the mutant transfectant demonstrated the production of an erroneously spliced mRNA with exon 6 skipping, whereas a normal splicing occurred in the wide type transfectant. The aberrant mRNA produced from the F7 c.572‐1G>A mutant allele is responsible for the factor VII deficiency in this pedigree.
Caveolin‐1 is a novel immunohistochemical marker to differentiate epithelioid mesothelioma from lung adenocarcinoma
Authors: Amatya Vishwa Jeet , Takeshima Yukio , Kohno Hidekazu , Kushitani Kei , Yamada Taketo , Morimoto Chikao , Inai Kouki
Published: July 2009

Aims:  The incidence of mesothelioma is increasing in Europe, Japan and other developing countries. There is difficulty in the accurate diagnosis of mesothelioma and its differentiation from lung adenocarcinoma. Mesothelioma shows a complex immunohistochemical profile. Therefore, the use of a immunohistochemical panel that includes both positive and negative mesothelial markers has become a general rule for its accurate diagnosis. However, they are still not sufficient. The aim was to assess the diagnostic utility of caveolin‐1 (Cav‐1), which is expressed in endothelial cells, alveolar type I pneumocytes and mesothelial cells, as a novel positive marker of mesothelioma.

Methods and results:  An immunohistochemical study of 80 cases of epithelioid mesothelioma and 80 cases of lung adenocarcinoma was performed for the analysis of the expression of Cav‐1 and other markers. Cav‐1 expression with a membranous and/or cytoplasmic pattern was found in all of the epithelioid mesothelioma. Of these, 42 cases (52.5%) showed Cav‐1 expression in >50% of tumour cells, 34 cases (42.5%) in 6–50% of tumour cells, and four cases (5.0%) in <5% of tumour cells. In contrast, only six cases (7.5%) of lung adenocarcinoma showed focal Cav‐1 expression in the cytoplasm of the tumour cells. The sensitivity and specificity of Cav‐1 expression for the differentiation of epithelioid mesothelioma from lung adenocarcinoma were 100 and 92.5%, respectively. This is comparable or even superior to that of currently available positive markers such as calretinin or D2‐40.

Conclusions:  Cav‐1 is a novel immunohistochemical marker for the differentiation of epithelioid mesothelioma from lung adenocarcinoma.
Expression and prognostic significance of cyclin B1 and cyclin A in non‐small cell lung cancer
Authors: Cooper Wendy A , Kohonen‐Corish Maija R J , McCaughan Brian , Kennedy Catherine , Sutherland Robert L , Lee Cheok Soon
Published: July 2009

Aims:  Aberrant expression of cell cycle regulators has been implicated in the pathogenesis of many neoplasms, including non‐small cell lung cancer (NSCLC). The aim was to examine the expression and prognostic value of cyclin B1 and cyclin A, key regulators of the G2/M checkpoint of the cell cycle, in NSCLC and bronchial precursor lesions.

Methods and results:  Immunohistochemical expression of cyclin B1 and A was examined in 90 cases of stage I–II primary NSCLC and bronchial precursor lesions using tissue microarrays. Increased cyclin B1 and A expression was found in 40.9 and 58.9% of NSCLC cases, respectively, and was significantly higher in primary NSCLC, lymph node metastases and some bronchial precursor lesions compared with normal bronchial epithelium. Increased expression of cyclin A and cyclin B1 correlated with tumour type, poorly differentiated tumours and male gender. A significant association was found between increased cyclin B1 expression and reduced survival using Kaplan–Meier survival analysis. On multivariate analysis, cyclin B1 was not an independent prognostic factor (P = 0.067). Cyclin A expression was not associated with survival.

Conclusions:  Cyclin B1 and cyclin A are aberrantly expressed in NSCLC and some precursor lesions. Cyclin B1, but not cyclin A, shows some promise as a potential prognostic marker in NSCLC.
Role of a fetal defence mechanism against oxidative stress in the aetiology of preeclampsia
Authors: Wruck Christoph Jan , Huppertz Berthold , Bose Patrick , Brandenburg Lars‐Ove , Pufe Thomas , Kadyrov Mamed
Published: July 2009

Aims:  Increasing evidence suggests that oxidative stress may play a key role in the aetiology of preeclampsia (PE). The aim of this study was to elucidate the placental defence mechanisms employed against oxidative stress and, in particular, the specific role of nuclear factor erythroid 2‐related factor 2 (Nrf2).

Methods and results:  Expression of Nrf2 in third‐trimester placental tissue was compared in preeclamptic and normal gestation‐matched controls. PE was associated with increased Nrf2 activity within cytotrophoblastic nuclei. Nrf2 expression was restricted to proliferative and early post‐proliferative cytotrophoblast only. Syncytiotrophoblast was immunonegative for Nrf2 in both controls and preeclamptic placentas.

Conclusions:  Nrf2 is exclusively active within cytotrophoblast, strongly suggesting that these cells are the origin of Nrf2‐dependent gene products. Syncytiotrophoblast is transcriptionally inactive; therefore in times of oxidative stress essential cytoprotective enzymes must be derived from the cytotrophoblast. Excessive cytotrophoblastic turnover causes disproportionate release of toxic placental factors, manifesting as PE and endangering maternal health. Increased cytotrophoblastic proliferation/fusion could thus be interpreted as a fetal defence mechanism, initiated in response to the requirements of vulnerable syncytiotrophoblast. We therefore propose a direct relationship between fetal defence against oxidative stress and consequent placental toxicity as part of the aetiology of this complex maternal disease.