bluuebunny/crossref_metadata_2025 huggingface dataset:
The Problem of Woman as Hero in the Work of Joseph Campbell
Authors: Nicholson Sarah
Published: December 2010

Through the frame of the Sumerian myth of Inanna, this essay explores Joseph Campbell’s body of work on the hero’s journey and living mythology. Particular focus is placed on examining both the place of woman as hero and the symbol of woman for the (male) hero in Campbell’s work. This essay suggests that Campbell’s theories present both possibilities and problems from the perspective of feminist analysis for the representation of woman as hero.
Friends in Need: The Protective Effect of Social Relationships Under Low-Safety Climate
Authors: Yagil Dana , Luria Gil
Published: December 2010

Previous studies have explored the role of social relationships, mainly with the supervisor, in promoting a high organizational safety climate. Not much is known, however, about the effect of social relationships when the safety climate is low. This study explored whether high-quality social relationships could compensate for a low level of safety climate. Hypotheses were tested among 673 employees and 46 managers from 46 departments in 11 manufacturing organizations in Israel. Results of both partial least squares and mixed-model procedures showed that employees’ climate perceptions mediate the relationship of supervisors’ climate perceptions with employees’ safety behavior. In addition, employees’ climate perceptions interacted with the quality of relationships with colleagues to affect safety behavior. However, the quality of the relationship with supervisors did not moderate the relationship between supervisors’ and employees’ climate perceptions. The results suggest that high-quality social relationships with colleagues could buffer the effects of low-level safety climate.
Doing Good and Doing Better despite Negative Information?: The Role of Corporate Social Responsibility in Consumer Resistance to Negative Information
Authors: Eisingerich Andreas B. , Rubera Gaia , Seifert Matthias , Bhardwaj Gunjan
Published: December 2010

Despite increased research on the various effects of Corporate Social Responsibility (CSR), the question of whether CSR is worthwhile for firms still remains to be addressed. Prior work suggests that CSR offers firms insurance-like protection against negative publicity due to greater levels of goodwill with various stakeholders. Yet, we still miss an answer to the following question: How effective, if at all, is CSR in insulating firms from scrutiny compared to other important marketing measures, such as customer orientation and service quality orientation? This study develops and empirically tests a theoretical framework that demonstrates the relative impact of CSR on consumer resistance to negative information when confronted with negative information about a firm. The results demonstrate that CSR shields firms from negative information about CSR practices but not information related to firms’ core service offerings. Managerially, the findings demonstrate that CSR may offer less of blanket insurance than assumed in previous research. Furthermore, results indicate that firms with a consumer base of experts should favor a focus on service quality orientation over CSR; conversely, when consumers are novices firms should focus on CSR for greater consumer resistance to negative information.
Magnetic resonance active lesions as individual-level surrogate for relapses in multiple sclerosis
Authors: Sormani Maria Pia , Stubinski Bettina , Cornelisse Peter , Rocak Sanda , Li David , Stefano Nicola De
Published: December 2010

Background: Use of quantitative magnetic resonance imaging (MRI) metrics as surrogates for clinical outcomes in multiple sclerosis (MS) trials is controversial.

Objectives: We sought to validate, at the individual-patient level, the number of MRI active lesions, as a surrogate marker for relapses in MS.

Methods: Individual-patient data from two large, placebo-controlled clinical trials of subcutaneous interferon β-1a in patients with relapsing–remitting or secondary progressive (SP) MS were analysed separately and as pooled data. The four Prentice criteria were applied to assess surrogacy for the number of new T2 MRI lesions. The predictive value of short-term treatment effects on this MRI marker for longer-term clinical relapses was also assessed.

Results: All Prentice criteria were satisfied. The number of new T2 MRI lesions correlated with the number of relapses over the follow-up period. The proportion of treatment effect on relapses accounted for by the effect of treatment on new T2 MRI lesions over 2 years was 53% in patients with relapsing–remitting MS, 67% in patients with secondary progressive MS, and 62% in pooled data. In the pooled data, treatment effects on new lesions over 1 year mediated a good proportion (70%) of effects on relapses over the subsequent year.

Conclusions: This study provides evidence that new T2 MRI lesion count is a surrogate for relapses in patients with MS treated with interferon or drugs with a similar mechanism of action. Short-term treatment effects on this MRI measure can predict longer-term effects on relapses.
Ivabradine: a new rate-limiting therapy for coronary artery disease and heart failure
Authors: Rushworth Gordon F. , Lambrakis Philippe , Leslie Stephen J.
Published: December 2010

Ivabradine is a new bradycardic agent acting on the If channels of sinoatrial nodal cells to decrease the rate of diastolic depolarization and thus heart rate. The benefit of ivabradine over other negatively chronotropic agents is its absence of negative inotropy. Effective management of coronary artery disease, in terms of reducing morbidity and mortality, is reliant on controlling heart rate. Ivabradine has been shown to safely and effectively reduce heart rate without compromising cardiac function in patients with coronary artery disease and more recently in patients with heart failure and raised heart rate. Furthermore, ivabradine has been shown to have a favourable side-effect profile compared with alternative bradycardic agents. This article reviews the evidence for ivabradine in coronary artery disease and heart failure and compares its safety with alternative bradycardic agents for these conditions.
Creating the Carbon Market Institution: Analysis of the Organizations and Relationships That Build the Market
Authors: Knox-Hayes Janelle
Published: December 2010

Countries around the world are developing carbon emission markets as a governance mechanism to reduce greenhouse gas emissions and mitigate anthropogenic climate change. These markets are social institutions, designed to solve the transnational collective action problem of climate change. This paper explores the development of carbon emission markets from an institutional perspective to understand how market networks specifically and social institutions in general are constructed. Drawing on seminal work of institutional theorists and economic sociologists, this paper explores the way in which organizations build the institution of the carbon markets. As this paper aims to demonstrate, a number of public and private organizations, rather than regulatory bodies, build and operationalize the market. The paper analyses how networks of organizations develop the three pillars of the carbon market institution: regulative, normative and cultural-cognitive constructs. Since organizations build the institutional pillars of the carbon market network, the strength of the institution cannot be determined by regulation alone. Certainly regulation gives the carbon markets credibility, but their ability to become an institution of common practice relies on the strength and embeddedness of the organizations that build them. The paper concludes by suggesting that, while the carbon market institution serves to communicate and disseminate a common social value of reducing emissions, it generates a dangerous over-reliance on markets to address environmental concerns.
Peripheral Financialization and Vulnerability to Crisis: A Regulationist Perspective
Authors: Becker Joachim , Jäger Johannes , Leubolt Bernhard , Weissenbacher Rudy
Published: December 2010

The current crisis confirmed that highly financialized regimes of accumulation are extremely crisis-prone. Most of the literature on financialization is focused on the economies of the centre. This paper analyses the peculiarities of financialization in the periphery, which is characterized by a high degree of extraversion and/or by considerable socio-economic heterogeneity. The theory of regulation permits analysis of different forms of financialization and the social dynamics linked with them. In contrast to Keynesian approaches, the state, international organizations and social forces shaping norms and policies are an explicit part of the theory. This allows for looking at policy-making within the analysis. Such an analysis enables us to explain policy changes (or lack of them) that are crucial for the processes of financialization and de-financialization in the periphery.
International Financialization and Depreciation: The Brazilian Real in the International Financial Crisis
Authors: Kaltenbrunner Annina
Published: December 2010

Despite sound macroeconomic fundamentals, the Brazilian currency, the real, experienced one of the world's largest exchange rate depreciations during the recent international financial crisis. This depreciation resulted from Brazil's rising ‘international financialization’, i.e. the increased participation of foreign investors in short-term domestic Brazilian assets. One important manifestation of this process, in particular, was the increased internationalization of the Brazilian real, which has become one of the most widely traded emerging-market currencies. However, the rising influence of international investors on Brazil's domestic currency weakened its exchange rate management during the international financial crisis as rapid international portfolio adjustment led to the real's sharp depreciation. Such exchange rate volatility has important implications for macroeconomic policy, especially exchange rate management, since, in the presence of increased international financialization, the standard prudent macroeconomic management that has been advocated by mainstream economics will prove inadequate — and might even undermine efforts — to maintain financial stability.
Two Waves of Globalization in the Istanbul Stock Exchange since 1985 and the Evolution of the Domestic Retail Investor
Authors: Tarim Emre
Published: December 2010

This paper reviews the quarter century of the Istanbul Stock Exchange (ISE) since its opening in 1985. The review focuses on the ISE's articulation to the global financial system in two different macro-economic modalities in the 1990s and the new millennium and its repercussions for domestic retail investors (DRIs). It is argued that macroeconomic business cycles and inadequate institutionalization of the ISE in the 1990s and early 2000s have generated a domestic investor profile which is short-termist, opportunistic and relatively ill-informed about the markets in general and fundamentals of equity investment in particular. The post-2000-01 crisis period has structurally transformed the Turkish economy and boosted the ISE's performance with a new wave of global institutional investor interest. Despite these positive changes, the domestic retail investor profile of the 1990s has largely remained the same in the present decade but with positive aggregate market returns for domestic investors and better and more democratic access to market information and knowledge.
From 'Anti-Scot', to 'Anti-Scottish Sentiment': Cultural Nationalism and Scottish Song in the Late Eighteenth to Nineteenth Centuries
Authors: McAulay Karen E
Published: December 2010

The unique appeal of Scottish song has resulted in considerable interest in the repertoire for over three centuries. Two particular English scholars provoked controversy with their own published song collections, one of Scottish songs, and the other largely of English songs. In each case, the questions of origin and concomitant cultural capital loomed large. In the lateeighteenth century, Joseph Ritson published his two-volume Scotish Song, despite having signed himself as 'Anti-Scot' ten years earlier, in 1784. Meanwhile, William Chappell's Popular Music of the Olden Time was published in the mid-nineteenth century, appearing in subsequent editions until the early twentieth century. Chappell stood accused of being anti-Scottish by song collectors north of the Border. The background to the accusations, and indeed the subsequent history of his book posthumously, show the situation to have been more complex than one would at first imagine. Both stories demonstrate the fact that information history embraces more than just the printed word, and underline the importance of national and cultural considerations in the study of popular traditions. We owe some of our current understanding to the far-sightedness of two further collectors, David Laing and Andrew Wighton, whose papers survive in major collections to this day.
Adsorption of adenine, cytosine, uracil, ribose, and phosphate by Mg-exchanged montmorillonite
Authors: Hashizume H. , van der Gaast S. , Theng B. K. G.
Published: December 2010

We have determined the adsorption of RNA components (adenine, cytosine, uracil, ribose and phosphate) by Mg2+-exchanged montmorillonite. The isotherms for adenine, cytosine and uracil were of the C-type, the amount adsorbed increasing linearly with the equilibrium solute concentration. All three nucleic acid bases were apparently adsorbed by coordination to Mg2+ions through a water bridge. Very little ribose was adsorbed by Mg-exchanged montmorillonite. The isotherm for phosphate was of the L-type. The plateau value of about 0.012 mmol g–1indicated that phosphate adsorbed on the edge surface of montmorillonite. At comparable solute concentrations, adsorption decreased in the order adenine > cytosine > uracil. This observation reflects differences in basicity, size, and aqueous solubility among the three compounds.
Crystal chemistry of natural layered double hydroxides. I. Quintinite-2H-3c from the Kovdor alkaline massif, Kola peninsula, Russia
Authors: Krivovichev S. V. , Yakovenchuk V. N. , Zhitova E. S. , Zolotarev A. A. , Pakhomovsky Y. A. , Ivanyuk G. Yu.
Published: December 2010

The crystal structure of quintinite-2H-3c, [Mg4Al2(OH)12](CO3)(H2O)3, from the Kovdor alkaline massif, Kola peninsula, Russia, was solved by direct methods and refined to an agreement index (R1) of 0.055 for 484 unique reflections with |Fo| ≥ 4σF. The mineral is rhombohedral, R32, a = 5.2745(7), c = 45.36(1) Å. The diffraction pattern of the crystal has strong and sharp Bragg reflections having h–k = 3n and l = 3n and lines of weak superstructure reflections extended parallel to c* and centred at h–k ≠ 3n. The structure contains six layers within the unit cell with the layer stacking sequence of …AC=CA=AC=CA=AC=CA… The Mg and Al atoms are ordered in metal hydroxide layers to form a honeycomb superstructure. The full superstructure is formed by the combination of two-layer stacking sequence and Mg-Al ordering. This is the first time that a long-range superstructure in carbonate-bearing layered double hydroxide (LDH) has been observed. Taking into account Mg-Al ordering, the unique layer sequence can be written as …=Ab1C=Cb1A=Ab2C=Cb2A=Ab3C=Cb3A=… The use of an additional suffix is proposed in order to distinguish between LDH polytypes having the same general stacking sequence but with different c parameters compared with the ‘standard’ polytype. According to this notation, the quintinite studied here can be described as quintinite-2H-3c or quintinite-2H-3c[6R], indicating the real symmetry.
Crystal chemistry of natural layered double hydroxides. 3. The crystal structure of Mg,Al-disordered quintinite-2H
Authors: Zhitova E. S. , Yakovenchuk V. N. , Krivovichev S. V. , Zolotarev A. A. , Pakhomovsky Y. A. , Ivanyuk G. Yu.
Published: December 2010

Two crystals of Mg, Al-disordered quintinite-2H (Q1 and Q2), [Mg4Al2(OH)12](CO3)(H2O)3, from the Kovdor alkaline massif, Kola peninsula, Russia, have been characterized chemically and structurally. Both crystals have hexagonal symmetry, P63/mcm, a = 3.0455(10)/3.0446(9), c = 15.125(7)/15.178(5) Å, V = 121.49(8)/121.84(6) Å3. The structures of the two crystals have been solved by direct methods and refined to R1 = 0.046 and 0.035 on the basis of 76 and 82 unique observed reflections for Q1 and Q2, respectively. Diffraction patterns obtained using an image-plate area detector showed the almost complete absence of superstructure reflections which would be indicative of the Mg-Al ordering in metal hydroxide layers, as has been observed recently for other quintinite polytypes. The crystal structures are based on double hydroxide layers [M(OH)2] with an average disordered distribution of Mg2+ and Al3+ cations. Average  bond lengths for the metal site are 2.017 and 2.020 Åfor Q1 and Q2, respectively, and are consistent with a highly Mg-Al disordered, average occupancy. The layer stacking sequence can be expressed as …=AC=CA=…, corresponding to a Mg-Al-disordered 2H polytype of quintinite. The observed disorder is probably the result of a relatively high temperature of formation for the Q1 and Q2 crystals compared to ordered polytypes. This suggestion is in general agreement with the previous observations which demonstrated, for the Mg-Al system, a higher-temperature regime of formation of the hexagonal (or pseudo-hexagonal in the case of quintinite-2H-3c) 2H polytype in comparison to the rhombohedral (or pseudo-rhombohedral in the case of quintinite-1M) 3R polytype.
The electrical conductivity of dry polycrystalline olivine compacts at high temperatures and pressures
Authors: Dai Lidong , Li Heping , Li Chunhai , Hu Haiying , Shan Shuangming
Published: December 2010

The electrical conductivity of dry polycrystalline olivine compacts (hot-pressed and sintered pellets) was measured at pressures of 1.0–4.0 GPa, at temperatures of 1073–1423 K, and at different oxygen fugacities via the use of a YJ-3000t multi-anvil press. Oxygen fugacity was controlled successfully by means of five solid buffers: Fe3O4-Fe2O3, Ni-NiO, Fe-Fe3O4, Fe-FeO and Mo-MoO2. Within the selected frequency range of 102–106 Hz, the experimental results indicate that the grain interior conduction mechanism is characterized by a semi-circular curve on an impedance diagram. As a function of increasing pressure, the electrical conductivity of polycrystalline olivine compacts decreases, whereas the activation enthalpy and the temperature-independent pre-exponential factors increase slightly. The activation energy and activation volume of polycrystalline olivine compacts were determined to be 141.02±2.53 kJ/mol and 0.25±0.05 cm3/mol, respectively. At a pressure of 4.0 GPa, electrical conductivity was observed to increase as a function of increasing oxygen fugacity, and the relationship between electrical conductivity and oxygen fugacity can be described as log10 (σ) = (2.47±0.085) + (0.096±0.023)×log10fO2 + (–0.55±0.011)/T, which presents the exponential factor q (˜0.096). Our observations demonstrate that the primary conduction mechanism for polycrystalline olivine compacts is a small polaron.
Kirschsteinite in the Capo di Bove melilite leucitite lava (cecilite), Alban Hills, Italy
Authors: Melluso L. , Conticelli S. , de' Gennaro R.
Published: December 2010

Kirschsteinite (mainly CaFeSiO4), in association with forsterite-fayalite solid solutions, melilite, clinopyroxene, leucite, nepheline and several minor phases, is reported for the first time in the 290 ka Capo di Bove melilite-leucitite lava flow of the Alban Hills volcanic complex (Italy). Kirschsteinite appears very late in the crystallization sequence, as indicated by textural and chemical evidence (Mg# ≈ 25). It shows significant solid solution towards fayalite, and is found with groundmass phases indicating a relatively low-temperature melt composition more silica-undersaturated than phonolite (i.e. devoid of alkali feldspar). This clearly points to the very silica-undersaturated nature of almost all the Alban Hills volcanic rocks.
The decomposition of konyaite: importance in CO2fixation in mine tailings
Authors: Mills S. J. , Wilson S. A. , Dipple G. M. , Raudsepp M.
Published: December 2010

The sodium-magnesium hydrated double salt konyaite, Na2Mg(SO4)2·5H2O, has been studied by single-crystal X-ray diffraction and thermogravimetry on synthetic samples and by quantitative X-ray diffraction utilizing the Rietveld method on natural samples from the Mount Keith mine, Western Australia. Konyaite crystallizes in space groupP21/c, with the cell parameters:a= 5.7594(10),b= 23.914(4),c= 8.0250(13) Å, β = 95.288(9)°,V= 1100.6(3) Å3and Z = 4. The crystal structure has been refined toR1= 3.41% for 2155 reflections [Fo>4σ(Fo)] and 6.44% for all 3061 reflections, with all atoms located.

Quantitative phase analysis utilizing the Rietveld method was undertaken on five samples of konyaite-bearing mine tailings from the Mount Keith Nickel Mine, Western Australia. Konyaite was found to decompose over time and after 22 months had transformed to other sulphate and amorphous phases. Blödite did not increase in any ofthe samples indicating that konyaite may not always transform to blödite. Over the same time frame, synthetic konyaite completely decomposed to a mixture of thenardite (Na2SO4), hexahydrite (MgSO4·6H2O), blödite (Na2Mg(SO4)2·4H2O) and löweite (Na12Mg7(SO4)13). Detection of konyaite and other Mg-rich sulphates is important in terms of CO2fixation. Magnesium bound to sulphate mineral phases reduces the overall potential of tailings piles to lock up atmospheric carbon in Mg carbonates, such as hydromagnesite. Amorphous sulphates are also highly reactive and may contribute to acid mine drainage ifpresent in large quantities, and may dissolve carbonate phases which have already sequestered carbon.
Natropharmacoalumite, NaAl4[(OH)4(AsO4)3].4H2O, a new mineral of the pharmacosiderite supergroup and the renaming of aluminopharmacosiderite to pharmacoalumite
Authors: Rumsey M. S. , Mills S. J. , Spratt J.
Published: December 2010

Natropharmacoalumite, ideally NaAl4[(OH)4(AsO4)3]·4H2O, is a new mineral from the Maria Josefa Gold mine, Rodalquilar, Andalusia region, Spain. It occurs as colourless, intergrown cubic crystals with chenevixite, kaolinite, jarosite and indeterminable mixtures of Fe and Sb oxyhydroxides. Individual crystals are up to 0.5 mm on edge, although crystals are more commonly ˜0.25 mm across and occur in patchy aggregates several millimetres across. The mineral is transparent with a vitreous to adamantine lustre. It is brittle with an imperfect cleavage, irregular fracture and a white streak. The Mohs hardness is ˜2.5 with a calculated densityof 2.56 g cm–3 for the empirical formula. Electron microprobe analyses yielded Na2O 2.52%, K2O 1.49%, Al2O3 29.50%, As2O5 48.84% and H2O was calculated in line with the structural analysis as 16.28% totalling 98.63%. The empirical formula, based upon 20.21 oxygen atoms, is [Na0.57K0.22(H3O)0.21]Σ1.00Al4.05(As2.97O12)(OH)4·4H2O. The five strongest lines in the X-ray powder diffraction pattern are [dobs(Å), Iobs,(hkl)]: 7.759,100,(100); 4.473,40,(111); 3.870,50,(200); 2.446,9,(301); 2.331,12,(311). Natropharmacoalumite is cubic, space group with a = 7.7280(3) Å, V = 461.53(3) Å3 and Z = 1. The crystal structure was solved by direct methods and refined to R1 = 0.063 for 295 reflections with F>4σ(F). The structure conforms broadly to that of the general pharmacosiderite structure type, with Na as the dominant cation in cavities of strongly distorted Al octahedra and As tetrahedra. A new group nomenclature system for minerals with the pharmacosiderite structure has been established, including the renaming of aluminopharmacosiderite to pharmacoalumite.
RUNX1 mutations are frequent in de novo AML with noncomplex karyotype and confer an unfavorable prognosis
Authors: Schnittger Susanne , Dicker Frank , Kern Wolfgang , Wendland Nicole , Sundermann Jana , Alpermann Tamara , Haferlach Claudia , Haferlach Torsten
Published: December 2010

Analyses of 164 RUNX1 mutations (RUNX1mut) in 147 of 449 patients (32.7%) with normal karyotype or noncomplex chromosomal imbalances were performed. RUNX1mut were most frequent in acute myeloid leukemia French-American-British classification M0 (65.2%) followed by M2 (32.4%) and M1 (30.2%). Considering cytogenetics, RUNX1mut were most frequent in cases with +13 (27 of 30, 90%), whereas frequencies were similar in other cytogenetic groups (26%-36%). The molecular genetic markers most frequently associated with RUNX1mut were partial tandem duplication in the MLL gene (19.7%), internal tandem duplication in the FLT3 gene (FLT3-ITD; 16.3%), and NRAS mutations (9.5%). Patients with RUNX1mut had shorter overall and event-free survival compared with RUNX1 wild-type cases (median, 378 days vs not reached, P = .003; and median, 285 vs 450 days, P = .003, respectively). In addition, it was shown that the adverse effect of RUNX1 was independent of the adverse effect of FLT3-ITD as well as of the high frequency of prognostically favorable NPM1mut and CEBPAmut in the RUNX1wt group. No effect of the type or localization of the individual RUNX1 mutations was observed. Multivariate analysis showed independent prognostic relevance for overall survival for RUNX1mut (P = .029), FLT3-ITD (P = .003), age (P < .001), and white blood cell count (P < .002).
Comparison of treatment strategies for patients with intestinal diffuse large B-cell lymphoma: surgical resection followed by chemotherapy versus chemotherapy alone
Authors: Kim Seok Jin , Kang Hye Jin , Kim Jin Seok , Oh Sung Yong , Choi Chul Won , Lee Soon Il , Won Jong Ho , Kim Min Kyoung , Kwon Jung Hye , Mun Yeung-Chul , Kwak Jae-Yong , Kwon Jung Mi , Hwang In Gyu , Kim Hyo Jung , Park Jinny , Oh Sukjoong , Huh Jooryung , Ko Young Hyeh , Suh Cheolwon , Kim Won Seog
Published: December 2010

The aim of this retrospective cohort study was to analyze the impact of surgery on the outcomes and qualities of life (QOL) in patients with intestinal diffuse large B-cell lymphoma (DLBCL). We assessed 345 patients with either localized or disseminated intestinal DLBCL and compared them according to treatment: surgical resection followed by chemotherapy versus chemotherapy alone. In patients with localized disease (Lugano stage I/II), surgery plus chemotherapy yielded a lower relapse rate (15.3%) than did chemotherapy alone (36.8%, P < .001). The 3-year overall survival rate was 91% in the surgery plus chemotherapy group and 62% in the chemotherapy-alone group (P < .001). The predominant pattern in the chemotherapy group was local relapse (27.6%). When rituximab was used with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP), there was no improvement of the outcomes in patients treated with primary surgical resection. The QOL of patients who underwent surgery and chemotherapy was lower than chemotherapy alone, but its difference was acceptable. Multivariate analysis showed that surgical resection plus chemotherapy was an independent prognostic factor for overall survival. Surgical resection followed by chemotherapy might be an effective treatment strategy with acceptable QOL deterioration for localized intestinal DLBCL. This study was registered at www.clinicaltrials.gov as #NCT01043302.
Antiviral and lung protective activity of a novel respiratory syncytial virus fusion inhibitor in a mouse model
Authors: Olszewska W. , Ispas G. , Schnoeller C. , Sawant D. , Van de Casteele T. , Nauwelaers D. , Van Kerckhove B. , Roymans D. , De Meulder M. , Rouan M.C. , Van Remoortere P. , Bonfanti J.F. , Van Velsen F. , Koul A. , Vanstockem M. , Andries K. , Sowinski P. , Wang B. , Openshaw P. , Verloes R.
Published: December 2010

Respiratory syncytial virus (RSV) causes bronchiolitis in young children and common colds in adults. There is no licensed vaccine, and prophylactic treatment with palivizumab is very expensive and limited to high-risk infants. Ribavirin is used as an antiviral treatment in infants and immunosuppressed patients, and its use is limited due to side-effects, toxicity to the recipient and staff, and evidence of marginal clinical efficacy. Therefore, we studied thein vivokinetics, and the antiviral and protective properties of a novel candidate for RSV disease treatment.

The drug is a small molecule (TMC353121) discovered by screening for fusion inhibitory properties against RSV in a cellular infection model. The pharmacokinetics of TMC353121 was studied in BALB/c mice and antiviral effects determined by testing viral loads in lung tissue by quantitative RT-PCR and plaque assay after intranasal RSV infection.

At doses of 0.25–10 mg·kg−1, TMC353121 significantly reduced viral load, bronchoalveolar lavage cell accumulation and the severity of lung histopathological change after infection. Treatment remained effective if started within 48 h of infection, but was ineffective thereafter.

Therefore, TMC353121 is a novel potent antiviral drug,in vivoreducing RSV replication and inhibiting consequential lung inflammation, with a great potential for further clinical development.
Mast cells promote lung vascular remodelling in pulmonary hypertension
Authors: Hoffmann J. , Yin J. , Kukucka M. , Yin N. , Saarikko I. , Sterner-Kock A. , Fujii H. , Leong-Poi H. , Kuppe H. , Schermuly R.T. , Kuebler W.M.
Published: December 2010

Left heart disease (LHD) frequently causes lung vascular remodelling and pulmonary hypertension (PH). Yet pharmacological treatment for PH in LHD is lacking and its pathophysiological basis remains obscure. We aimed to identify candidate mechanisms of PH in LHD and to test their relevance and therapeutic potential.

In rats, LHD was induced by supracoronary aortic banding. Whole genome microarray analyses were performed, candidate genes were confirmed by RT-PCR and Western blots and functional relevance was testedin vivoby genetic and pharmacological strategies.

In lungs of LHD rats, mast cell activation was the most prominently upregulated gene ontology cluster. Mast cell gene upregulation was confirmed at RNA and protein levels and remodelled vessels showed perivascular mast cell accumulations. In LHD rats treated with the mast cell stabiliser ketotifen, or in mast cell deficientWs/Wsrats, PH and vascular remodelling were largely attenuated. Both strategies also reduced PH and vascular remodelling in monocrotaline-induced pulmonary arterial hypertension, suggesting that the role of mast cells extends to non-cardiogenic PH.

In PH of different aetiologies, mast cells accumulate around pulmonary blood vessels and contribute to vascular remodelling and PH. Mast cells and mast cell-derived mediators may present promising targets for the treatment of PH.
Time interval to conversion of interferon-γ release assay after exposure to tuberculosis
Authors: Lee S.W. , Oh D.K. , Lee S.H. , Kang H.Y. , Lee C-T. , Yim J-J.
Published: December 2010

The proper interval for repeating an interferon-γ release assay (IGRA) among tuberculosis contacts with initially negative results is unknown. The interval for IGRA conversion after exposure to patients with active pulmonary tuberculosis in an outbreak setting was evaluated.

In a platoon of 32 soldiers, four active pulmonary tuberculosis patients, in addition to one index patient, were diagnosed during a contact investigation. For the other 27 contacts, a tuberculin skin test (TST) and QuantiFERON®TB-Gold In-Tube (QFT-GIT) assay were performed. For soldiers with a negative result on the initial QFT-GIT assay, the test was repeated at 2, 4, 8, 14, 18 and 30 weeks until positive conversion occurred. When conversion was identified, the subject was treated for latent tuberculosis infection.

Initially, 17 (63.0%) soldiers gave positive QFT-GIT results, whereas 21 (77.8%) showed positive TST results. Among 10 participants with initially negative QFT-GIT results, three showed conversion at 2 weeks, three at 4 weeks and three at 14 weeks. Conversion did not occur during the 30-week observation period in one contact.

Based on the tuberculosis exposure time-points among the contacts, IGRA conversion generally occurred 4–7 weeks after exposure, although it could occur as late as 14–22 weeks after exposure.
Long-term effects of lung cancer computed tomography screening on health-related quality of life: the NELSON trial
Authors: van den Bergh K.A.M. , Essink-Bot M.L. , Borsboom G.J.J.M. , Scholten E.T. , van Klaveren R.J. , de Koning H.J.
Published: December 2010

The long-term effects of lung cancer computed tomography (CT) screening on health-related quality of life (HRQoL) have not yet been investigated.

In the Dutch–Belgian Randomised Lung Cancer Screening Trial (NELSON trial), 1,466 participants received questionnaires before randomisation (T0), 2 months after baseline screening (screen group only; T1) and at 2-yr follow-up (T2). HRQoL was measured as generic HRQoL (12-item short-form questionnaire and EuroQoL questionnaire), anxiety (Spielberger State-Trait Anxiety Inventory) and lung cancer-specific distress (impact of event scale (IES)). Repeated measures of ANOVA were used to analyse differences between the screen and control groups, and between indeterminate (requiring a follow-up CT) and negative screening result groups.

At T0 and T2 there were no significant differences in HRQoL scores over time between the screen and control groups, or between the indeterminate or negative second-round screening result group. There was a temporary increase in IES scores after an indeterminate baseline result (T0: mean 4.0 (95% CI 2.8–5.3); T1: mean 7.8 (95% CI 6.5–9.0); T2: mean 4.5 (95% CI 3.3–5.8)).

At 2-yr follow-up, the HRQoL of screened subjects was similar to that of control subjects, the unfavourable short-term effects of an indeterminate baseline screening result had resolved and an indeterminate result at the second screening round had no impact on HRQoL.
IFN-γ response on T-cell based assays in HIV-infected patients for detection of tuberculosis infection
Authors: Latorre Irene , Martínez-Lacasa Xavier , Font Roser , Lacoma Alicia , Puig Jordi , Tural Cristina , Lite Josep , Prat Cristina , Cuchi Eva , Ausina Vicente , Domínguez Jose
Published: December 2010

Background

Individuals infected with human immunodeficiency virus (HIV) have an increased risk of progression to active tuberculosis following Mycobacterium tuberculosis infection. The objective of the study was to determine IFN-γ responses for the detection of latent tuberculosis infection (LTBI) with QuantiFERON-TB GOLD In Tube (QFT-G-IT) and T-SPOT.TB in HIV patients, and evaluate the influence of CD4 cell count on tests performance.

Methods

We studied 75 HIV patients enrolled for ongoing studies of LTBI with T-SPOT.TB, QFN-G-IT and TST. Mean CD4 cell counts ± standard deviation was 461.29 ± 307.49 cells/μl. Eight patients had a BCG scar.

Results

T-SPOT.TB, QFN-G-IT and TST were positive in 7 (9.3%), 5 (6.7%) and 9 (12%) cases, respectively. Global agreement between QFN-G-IT and T-SPOT.TB was 89% (κ = 0.275). The overall agreement of T-SPOT.TB and QFN-G-IT with TST was 80.8% (κ = 0.019) and 89% (κ = 0.373), respectively. We have found negative IFN-γ assays results among 2 BCG-vaccinated HIV-infected individuals with a positive TST. In non BCG-vaccinated patients, QFN-G-IT and TST were positive in 5 cases (7.5%) and T-SPOT.TB in 7 (10.4%). In contrast, in BCG-vaccinated patients, only TST was positive in 4/8 (50%) of the cases. The differences obtained in the number of positive results between TST and both IFN-γ assays in BCG vaccinated patients were significant (95% CI 3-97%, p = 0.046), however, the confidence interval is very wide given the small number of patients. In patients with CD4< 200, we obtained only one (5%) positive result with T-SPOT.TB; however, QFN-G-IT and TST were negative in all cases. On the contrary, percentages of positive results in patients with CD4> 200 were 10.9% (6/55), 9.1% (5/55) and 16.4% (9/55) with T-SPOT.TB, QFN-G-IT and TST, respectively.

Conclusions

IFN-γ tests have the benefit over TST that are less influenced by BCG vaccination, consequently they are more specific than TST. Although our number of patients with advance immunosuppression is limited, our study suggests that IFN-γ assays are influenced with level of immunosuppression. The use of IFN-γ assays could be a helpful method for diagnosing LTBI in HIV population.
Proteomic profiling of proteins associated with the rejuvenation of Sequoia sempervirens (D. Don) Endl
Authors: Chang Ing-Feng , Chen Peng-Jen , Shen Chin-Hui , Hsieh Tsung-Ju , Hsu Ya-Wen , Huang Bau-Lian , Kuo Ching-I , Chen Yu-Ting , Chu Hsiu-An , Yeh Kai-Wun , Huang Li-Chun
Published: December 2010

Background

Restoration of rooting competence is important for rejuvenation inSequoia sempervirens(D. Don) Endl and is achieved by repeatedly graftingSequoiashoots after 16 and 30 years of cultivationin vitro.

Results

Mass spectrometry-based proteomic analysis revealed three proteins that differentially accumulated in different rejuvenation stages, including oxygen-evolving enhancer protein 2 (OEE2), glycine-rich RNA-binding protein (RNP), and a thaumatin-like protein. OEE2 was found to be phosphorylated and a phosphopeptide (YEDNFDGNSNVSVMVpTPpTDK) was identified. Specifically, the protein levels of OEE2 increased as a result of grafting and displayed a higher abundance in plants during the juvenile and rejuvenated stages. Additionally,SsOEE2displayed the highest expression levels inSequoiashoots during the juvenile stage and less expression during the adult stage. The expression levels also steadily increased during grafting.

Conclusion

Our results indicate a positive correlation between the gene and protein expression patterns ofSsOEE2and the rejuvenation process, suggesting that this gene is involved in the rejuvenation ofSequoia sempervirens.
Characterization of influenza virus sialic acid receptors in minor poultry species
Authors: Kimble Brian , Nieto Gloria Ramirez , Perez Daniel R
Published: December 2010

It is commonly accepted that avian influenza viruses (AIVs) bind to terminal α2,3 sialic acid (SA) residues whereas human influenza viruses bind to α2,6 SA residues. By a series of amino acid changes on the HA surface protein, AIVs can switch receptor specificity and recognize α2,6 SA positive cells, including human respiratory epithelial cells. Animal species, like pigs and Japanese quail, that contain both α2,3 and α2,6 SA become ideal environments for receptor switching. Here, we describe the SA patterns and distributions in 6 common minor domestic poultry species: Peking duck, Toulouse geese, Chinese ring-neck pheasant, white midget turkey, bobwhite quail, and pearl guinea fowl. Lectins specific to α2,3 and α2,6 SA (Maakia amurensis agglutinin and Sambuca nigra agglutinin, respectively) were used to detect SA by an alkaline phosphotase-based method and a fluorescent-based method. Differences in SA moieties and their ability to bind influenza viruses were visualized by fluorescent labeling of 4 different H3N2 influenza viruses known to be specific for one receptor or the other. The geese and ducks showed α2,3 SA throughout the respiratory tract and marginal α2,6 SA only in the colon. The four other avian species showed both α2,3 and α2,6 SA in the respiratory tract and the intestines. Furthermore, the turkey respiratory tract showed a positive correlation between age and α2,6 SA levels. The fact that these birds have both avian and human flu receptors, combined with their common presence in backyard farms and live bird markets worldwide, mark them as potential mixing bowl species and necessitates improved surveillance and additional research about the role of these birds in influenza host switching.
Temporomandibular Joint Inflammation Activates Glial and Immune Cells in Both the Trigeminal Ganglia and in the Spinal Trigeminal Nucleus
Authors: Villa Giovanni , Ceruti Stefania , Zanardelli Matteo , Magni Giulia , Jasmin Luc , Ohara Peter T , Abbracchio Maria P
Published: December 2010

Background:

Glial cells have been shown to directly participate to the genesis and maintenance of chronic pain in both the sensory ganglia and the central nervous system (CNS). Indeed, glial cell activation has been reported in both the dorsal root ganglia and the spinal cord following injury or inflammation of the sciatic nerve, but no data are currently available in animal models of trigeminal sensitization. Therefore, in the present study, we evaluated glial cell activation in the trigeminal-spinal system following injection of the Complete Freund's Adjuvant (CFA) into the temporomandibular joint, which generates inflammatory pain and trigeminal hypersensitivity.

Results:

CFA-injected animals showed ipsilateral mechanical allodynia and temporomandibular joint edema, accompanied in the trigeminal ganglion by a strong increase in the number of GFAP-positive satellite glial cells encircling neurons and by the activation of resident macrophages. Seventy-two hours after CFA injection, activated microglial cells were observed in the ipsilateral trigeminal subnucleus caudalis and in the cervical dorsal horn, with a significant up-regulation of Iba1 immunoreactivity, but no signs of reactive astrogliosis were detected in the same areas. Since the purinergic system has been implicated in the activation of microglial cells during neuropathic pain, we have also evaluated the expression of the microglial-specific P2Y12receptor subtype. No upregulation of this receptor was detected following induction of TMJ inflammation, suggesting that any possible role of P2Y12in this paradigm of inflammatory pain does not involve changes in receptor expression.

Conclusions:

Our data indicate that specific glial cell populations become activated in both the trigeminal ganglia and the CNS following induction of temporomandibular joint inflammation, and suggest that they might represent innovative targets for controlling pain during trigeminal nerve sensitization.
Unusual histological findings after partial pancreaticoduodenectomy including benign multicystic mesothelioma, adenomyoma of the ampulla of Vater, and undifferentiated carcinoma, sarcomatoid variant: a case series
Authors: Lehwald Nadja , Cupisti Kenko , Baldus Stephan E , Kröpil Patric , Schulte am Esch Jan , Eisenberger Claus F , Knoefel Wolfram T
Published: December 2010

Introduction

The standard operation for carcinoma of the pancreatic head is a partial pancreaticoduodenectomy. Unusual histological findings may occasionally occur in the surgical specimen. We present three unusual histologic diagnoses after pancreaticoduodenectomy.

Case presentations

In the first case, an 86-year-old Caucasian woman was admitted with abdominal pain and nausea. Preoperative evaluation showed a 3 cm cystic lesion in the head of the pancreas. Pathology revealed a benign multicystic mesothelioma. In the second case, a 45-year-old Caucasian man complained of nausea, vomiting and general malaise for several months. Endoscopic retrograde cholangiopancreatographic examination and a computed tomography scan showed a stenosis of the distal bile duct secondary to a mass in the head of the pancreas and duodenum. Histology showed an adenomyoma of the ampulla. In the third case, a 59-year-old Caucasian man presented with chronic alcoholic pancreatitis. A computed tomography scan revealed a 3.5 cm lesion in the head of the pancreas with cystic and solid components. Pathology showed an undifferentiated carcinoma, sarcomatoid variant.

Conclusion

Partial pancreaticoduodenectomy is usually performed for ductal adenocarcinomas, neuroendocrine tumors or chronic pancreatitis. Compared to the majority of the above diagnoses, the three cases in our study are very rare. Benign multicystic mesothelioma is a very rare tumor that originates from the peritoneum. Although it demonstrates a benign clinical behaviour, it frequently recurs after resection. Adenomyoma of the bile duct or ampullary region is a very unusual, benign, localized lesion characterized by adenomyomatous hyperplasia. Undifferentiated carcinoma, sarcomatoid variant, is an aggressive tumor and is characterized by spindle cells. As the lesions were suspicious for carcinoma, partial pancreaticoduodenectomy was justified in all three patients. The histologic diagnosis after partial pancreaticoduodenectomy may differ from the preoperative and intraoperative findings. These cases demonstrate that a definitive diagnosis may only be obtained by a pathologic examination of the surgical specimen.
High-dose steroid therapy for idiopathic optic perineuritis: a case series
Authors: Tatsugawa Maria , Noma Hidetaka , Mimura Tatsuya , Funatsu Hideharu
Published: December 2010

Introduction

It has been reported that the prognosis of optic perineuritis may be poor when initiation of treatment is delayed. Here we report the successful treatment of three patients with idiopathic optic perineuritis, including two in whom initiation of therapy was delayed.

Case presentation

Three Japanese patients (two women aged 73 and 66 years, and one man aged 27 years) presented with loss of vision (for five months, several months, and two months respectively) and pain on eye movement in the third case only, and were diagnosed as having idiopathic optic perineuritis. Fat-suppressed T2-weighted magnetic resonance images showed high signal intensity areas around the affected optic nerves, suggesting the presence of optic perineuritis. Two patients received steroid pulse therapy and the third was given high-dose steroid therapy. The visual acuity improved in all three cases.

Conclusion

High-dose steroid therapy may be effective for idiopathic perineuritis in patients without optic nerve atrophy, even if initial treatment (including moderate-dose steroids) has failed.
Noise reduction and drift removal using least-squares support vector regression with the implicit bias term
Authors: Deng Xiaoying , Yang Dinghui , Peng Jiming , Guan Xin , Yang Baojun
Published: December 2010

Random noise and drifts often degrade the quality of the seismic data and harm further processing. The support vector machine (SVM) is a universal machine learning method based on the statistical learning theory, which has been widely used in classification and regression. On the basis of the least squares support vector regression (LS-SVR), we propose the least squares support vector regression with implicit bias term (ILS-SVR) to reduce the random noise and remove the drifts in seismic data. The proposed method stacks the weight vector and the bias term into a new vector, and incorporates the bias term into the objective function of the optimization problem in the LS-SVR model. As a result, for the translation invariant kernel we obtain a simpler solution that can be computed more efficiently than the LS-SVR. More importantly, the ILS-SVR with a Ricker wavelet kernel can not only effectively suppress the random noise, but also remove drifts in seismic data. Behind the proposed method, the implicit bias term and the special choice of the kernel (such as the Ricker wavelet kernel) are two key ingredients to remove drifts. We test the proposed method on both synthetic and real seismic data, and compare it with the ILS-SVR using the popular radial basis function (RBF) kernel, the [Formula: see text] prediction filtering, and the wavelet transform-based method. Our experimental results illustrate that the proposed algorithm achieves better performance over the other three algorithms.