bluuebunny/crossref_metadata_2025 huggingface dataset:
CEO Social Capital and Entrepreneurial Orientation of the Firm
Authors: Cao Qing , Simsek Zeki , Jansen Justin J. P.
Published: December 2012

Prior studies demonstrate the role of various facets of CEOs’ individual characteristics in shaping a firm’s entrepreneurial orientation (EO). We complement this line of research by theorizing and testing the impact of CEOs’ social capital on EO. From an original, multisource survey data set of 122 Chinese technology firms, we find that a CEO’s bonding social capital with organizational members from various functional units has an inverted U-shaped relationship with firm EO, while the CEO’s bridging social capital with the firm’s diverse set of external stakeholders has a positive association with EO. In addition, we find that the relationship between CEO bridging social capital and EO becomes stronger as the firm’s environmental instability increases.
Proceedings of the 2012 National Toxicology Program Satellite Symposium
Authors: Elmore Susan A. , Berridge Brian R. , Boyle Michael C. , Cora Michelle C. , Hoenerhoff Mark J. , Kooistra Linda , Laast Victoria A. , Morrison James P. , Rao Deepa , Rinke Matthias , Yoshizawa Katsuhiko
Published: December 2012

The 2012 annual National Toxicology Program (NTP) Satellite Symposium, entitled “Pathology Potpourri,” was held in Boston in advance of the Society of Toxicologic Pathology's 31st annual meeting. The goal of the NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers’ presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for audience voting or discussion. Some lesions and topics covered during the symposium include eosinophilic crystalline pneumonia in a transgenic mouse model; differentiating adrenal cortical cystic degeneration from adenoma; atypical eosinophilic foci of altered hepatocytes; differentiating cardiac schwannoma from cardiomyopathy; diagnosis of cardiac papillary muscle lesions; intrahepatocytic erythrocytes and venous subendothelial hepatocytes; lesions in Rathke’s cleft and pars distalis; pernicious anemia and megaloblastic disorders; embryonic neuroepithelial dysplasia, holoprosencephaly and exencephaly; and INHAND nomenclature for select cardiovascular lesions.
Occurrence of Spontaneous Amphophilic-Vacuolar Renal Tubule Tumors in Sprague-Dawley Rats from Subchronic Toxicity Studies
Authors: Crabbs Torrie A. , Frame Steve R. , Laast Victoria A. , Patrick Daniel J. , Thomas Johnson , Zimmerman Bevin , Hardisty Jerry F.
Published: December 2012

The low background incidence of tumors in rodents from subchronic toxicity studies makes it difficult to assess their relevance, especially when present only in treated animals. This report investigates the occurrence of renal tubule tumors (RTTs), specifically the amphophilic-vacuolar (AV) phenotypic variant, in young Sprague-Dawley (SD) rats from a survey of laboratories conducting subchronic toxicity studies spanning a period of 10 years (2002–2012). This survey establishes a general profile of tumor occurrence; it does not estimate overall incidence or prevalence. AV tumors are spontaneous, nontreatment-related tumors of familial origin, and morphologically distinct from conventional RTTs induced by exposure to renal carcinogens. They are composed of distinct lobules of large, round to polyhedral cells with vacuolated amphophilic to eosinophilic cytoplasm and prominent nucleoli. Data from five collaborating laboratories, representing 37 qualifying studies, are presented. In total, 58 renal tubule neoplasms were recorded in this data set. The AV tumor variant was reported more commonly than the conventional RTT ( n = 45 and 13, respectively), and it was recorded in both experimental ( n = 32) and control ( n = 13) groups. AV tumors occurred more often in females ( n = 34) than in males ( n = 11); conventional RTTs were recorded more often in males ( n = 9) than in females ( n = 4). AV tumors often occurred in more than one rat within the same study (up to 7) and were documented to occur in rats as young as 7 to 10 weeks of age. Results from this survey indicate that AV tumors are being reported more commonly in recent years; the majority ( n = 33) were reported in studies commencing since 2009. In conclusion, this study reaffirms that AV tumors are spontaneous, nontreatment-related lesions, and suggests that they may be more common than conventional RTTs in young SD rats. The authors propose that AV tumors be recorded separately from conventional RTTs in order to clearly distinguish these two renal tubule neoplasms from one another and allow for appropriate interpretation of a compound’s potential carcinogenic effect in the kidney.
Toxicant-associated Steatohepatitis
Authors: Wahlang Banrida , Beier Juliane I. , Clair Heather B. , Bellis-Jones Heather J. , Falkner K. Cameron , McClain Craig J. , Cave Matt C.
Published: December 2012

Hepatotoxicity is the most common organ injury due to occupational and environmental exposures to industrial chemicals. A wide range of liver pathologies ranging from necrosis to cancer have been observed following chemical exposures both in humans and in animal models. Toxicant-associated fatty liver disease (TAFLD) is a recently named form of liver injury pathologically similar to alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD). Toxicant-associated steatohepatitis (TASH) is a more severe form of TAFLD characterized by hepatic steatosis, inflammatory infiltrate, and in some cases, fibrosis. While subjects with TASH have exposures to industrial chemicals, such as vinyl chloride, they do not have traditional risk factors for fatty liver such as significant alcohol consumption or obesity. Conventional biomarkers of hepatotoxicity including serum alanine aminotransferase activity may be normal in TASH, making screening problematic. This article examines selected chemical exposures associated with TAFLD in human subjects or animal models and concisely reviews the closely related NAFLD and ALD.
Perceptions of surveillance: Reflexivity and trust in a mediatized world (the case of Sweden)
Authors: Jansson André
Published: December 2012

Even though the field of surveillance studies has expanded during the last decade, there is still a need for studies that empirically explain and contextualize people’s perceptions of the increasingly mediatized ‘surveillance society’. This article provides a ‘middle range’ social theorization, following Giddens, as well as an updated empirical account, based on a nationwide Swedish survey, of how various forms of surveillance are perceived as social phenomena. Through factor analysis three dimensions are elaborated: state surveillance, commercial surveillance and mediated interveillance. The article argues that the realm of interveillance blurs the line between systemic and social trust, and thus calls for context-specific modes of routinized reflexivity. Whereas such modes of boundary maintenance may potentially run across social lines of division, the results suggest that the management of interveillance primarily constitutes an instance of sociocultural structuration.
Intellectual Closure: A Theoretical Framework Linking Knowledge, Power, and the Corporate University
Authors: Subramaniam Mangala , Perrucci Robert , Whitlock David
Published: December 2012

Scholars have recently called attention to the changing nature of the American university in the wake of the current economic downturn. Considering the transformative nature of knowledge production in the United States, we introduce the concept of intellectual closure in illustration of the unintended outcomes of individual decisions and career trajectories as they operate under the forces of social closure. Intellectual closure is defined as subtle and hidden forms of constraint on individual agency. Intellectual closure includes calculative thinking about how to publish in flagship journals, avoidance of high-risk projects, and preference for short-term projects with more immediate rewards. Structural constraints, specifically within sociology, are enabling the emergence of narrower perspectives and eroding former professional norms as individual decisions aggregate, unintentionally, to constitute a more competitive discipline with narrower definitions of productivity and quality.
Feature ranking for support vector machine classification and its application to machinery fault diagnosis
Authors: Liu Zhiliang , Zuo Ming J , Xu Hongbing
Published: December 2012

This article provides a feature ranking criterion for multi-class support vector machine classification. In the proposed criterion, feature effectiveness is estimated for individual features by their contributions to class separability in the kernel space. Class separability, measured by cosine similarity, is defined by an objective function that consists of within-class and between-class separabilities. Feature ranking is achieved for individual features by sorting their effectiveness scores. The proposed criterion is validated on University of California Irvine benchmark datasets and also applied to pitting diagnosis for a planetary gearbox. The experimental results demonstrate that the proposed criterion of feature ranking is computationally economic and effective.
Finite element modelling of substrate thermal distortion in direct laser additive manufacture of an aero-engine component
Authors: Marimuthu S , Clark D , Allen J , Kamara AM , Mativenga P , Li L , Scudamore R
Published: December 2012

The shape complexity of aerospace components is continuously increasing, which encourages researchers to further refine their manufacturing processes. Among such processes, blown powder direct laser deposition process is becoming an economical and energy efficient alternative to the conventional machining process. However, depending on their magnitudes, the distortion and residual stress generated during direct laser deposition process can affect the performance and geometric tolerances of manufactured components. This article reports an investigation carried out using the finite element analysis method to predict the distortion generated in an aero-engine component produced by the direct laser deposition process. The computation of the temperature induced during the direct laser deposition process and the corresponding distortion on the component was accomplished through a three-dimensional thermo-structural finite element analysis model. The model was validated against measured distortion values of the real component produced by direct laser deposition process using a Trumpf DMD505 CO2 laser. Various direct laser deposition fill patterns (orientation strategies/tool movement) were investigated in order to identify the best parameters that will result in minimum distortion.
Modelling and optimization of the cutting conditions in hard turning of high-alloy white cast iron (Ni-Hard)
Authors: Yücel Emre , Günay Mustafa
Published: December 2012

The aim of this study is to model and optimize the cutting conditions for the cutting force ( Fc) and average surface roughness ( Ra) that result from the machining of high-alloy white cast iron (Ni-Hard). The hard turning experiments were carried out on a CNC lathe with ceramic and CBN inserts. Cutting tool material, cutting speed, feed rate and depth of cut were chosen as the cutting conditions (control factors). Taguchi’s L18 orthogonal array was used for design of experiment. Optimum levels of the cutting conditions were determined using signal-to-noise ( S/N) ratio, which was calculated for machining output variables ( Fc and Ra) according to the ‘the-smaller-the-better’ approach. The effects of the cutting conditions on machining output variables were evaluated by the analysis of variance. The analysis of variance results showed that the depth of cut and feed rate were the most significant factors on Fc and Ra, respectively. Besides, the optimal cutting conditions for main cutting force and surface roughness were found at the different levels.
Combined control strategy using internal model control and adaptive inverse control for electro-hydraulic shaking table
Authors: Shen Gang , Zhu Zhencai , Tang Yu , Zhang Lei , Liu Guangda , Zhao Jinsong , Yang Chifu , Han Junwei
Published: December 2012

An electro-hydraulic shaking table is a useful experimental apparatus to real-time replicate the desired acceleration signal for evaluating the performance of the tested structural systems. The article proposes a combined control strategy to improve the tracking accuracy of the electro-hydraulic shaking table. First, the combined control strategy utilizes an adaptive inverse control as a feedforward controller for extending the acceleration frequency bandwidth of the electro-hydraulic shaking table when the estimated plant model may be a nonminimum phase system and its inverse model is an unstable system. The adaptive inverse control feedforward compensator guarantees the stability of the estimated inverse transfer function. Then, the combined control strategy employs an improved internal model control for obtaining high fidelity tracking accuracy after the modeling error between the estimated inverse transfer function using adaptive inverse control and the electro-hydraulic shaking table actual inverse system is improved by the improved internal model control. So, the proposed control strategy combines the merits of adaptive inverse control feedforward compensator and improved internal model control. The combined strategy is programmed in MATLAB/Simulink, and then is compiled to a real-time PC system with xPC target technology for implementation. The experimental results demonstrate that a better tracking performance with the proposed combined control strategy is achieved in an electro-hydraulic shaking table than with a conventional controller.
Application of the geometry of conjugate curves to the design of internal-meshing rotary compressors
Authors: Feng Shiyu , Wang Zanshe , Gao Xiufeng , Li Yun , Gu Zhaolin
Published: December 2012

The internal-meshing rotary compressor can be applied to the CO2 transcritical refrigeration cycle due to its simple structure, self-balanced initial mass, and high pressure endurance. Because of the different fluids transmitted by compressor and pump, the design method of the internal meshing rotary pump cannot be entirely and directly employed. In order to simplify the further study of the internal-meshing rotary compressors, the essential profile equations for the inner and outer rotors are derived and explicitly formulated based on the equidistant curve of curtate epicycloid and the multi-section circular arc, respectively. Then, the relationship between the meshes of the inner and outer rotors, the position of the instantaneous center, the meshing range of the tooth tip arc, and the modification of the profiles are discussed. These basic geometric theories are expected to lay the principles for the design of the compressor of interest.
Mobility and kinematic simulations of cyclically symmetric deployable truss structures
Authors: Chen Yao , Feng Jian , Fan Linzi
Published: December 2012

Based on the mechanism of four-fold rigid origami, this study proposes a type of deployable truss structures that consist of repetitive basic parts and retain full cyclic symmetry in the folding/deployment process. On the basis of the irreducible representations and the great orthogonality theorem, symmetry-adapted analysis using group theory is described to identify the symmetry of mobility and kinematic behavior. Equivalent three-dimensional pin-jointed frameworks are employed for the symmetric structures. To verify that the structures can be foldable while retaining their full symmetries, numerical simulations on a series of structures with different symmetries and geometries are carried out. An artificial damping is introduced to stabilize the nonlinear folding behavior with singularity. Symmetry-adapted mobility analysis reveals that the structures of this type can be continuously folded with one degree-of-freedoms. Numerical simulations using the nonlinear iterative method accurately predict the folding behavior, as the results agree very well with the theoretic value.
Optimal operation scheduling and platform track assignment in a passenger railway station
Authors: Jánošíková Ĺudmila , Kavička Antonín , Bažant Michael
Published: December 2012

This paper deals with selected problems encountered in the real-time operation of a passenger railway station. Delays to incoming trains can negate a valid timetable and track assignment plan. In such situations the dispatcher has to flexibly solve problems related to potential train routing conflicts. This paper models the dispatcher’s decision-making process using a mathematical programming approach. Inputs to the mathematical programming model reflect potential delays to incoming trains. Outputs from the model concentrate mainly on solving the following problems: first, which platform track is assigned to an arriving train, and second, how long connecting trains are allowed to wait for the delayed incoming train. The objective function applies a multi-criteria approach with two goals: to reduce the influence of the delays on departing trains (i.e. to minimise the deviations from the valid timetable), and, at the same time, to minimise the inconvenience caused to passengers. The proposed model can be used to support the dispatching control of real-time traffic or as a part of a railway station simulation model.
Simulation of gas flow and additional thrust with missile launching from concentric canister launcher
Authors: Fu Debin , Yu Yong
Published: December 2012

A computational fluid dynamics method has been applied to simulate the exhaust gas flow and the additional thrust during a missile launching from concentric canister launcher. The unsteady, axisymmetric Reynolds-averaged Navier–Stokes equations with renormalization group [Formula: see text] turbulence model are numerically solved here. The dynamic mesh method is utilized to simulate the movement of the missile. Computational fluid dynamics results show that the additional thrust is an important thrust and fluctuates with the movement of the missile for launching from concentric canister launcher. The mechanism for producing and influencing the additional thrust is typically relevant to the choking states of exhaust gases at the inlet and outlet of the annular tube of concentric canister launcher, responding to the jet impinging on the bottom of the launcher, the approximate wall jet, and the friction effect in the tube.
Buckling/post-buckling strength of friction stir welded aircraft stiffened panels
Authors: Murphy A , Ekmekyapar T , Özakça M , Poston K , Moore G , Elliott M
Published: December 2012

Assembling aircraft stiffened panels using friction stir welding offers potential to reduce fabrication time in comparison to current mechanical fastener assembly, making it economically feasible to select structurally desirable stiffener pitching and novel panel configurations. With such a departure from the traditional fabrication process, much research has been conducted on producing strong reliable welds, with less examination of the impact of welding process residual effects on panel structural behaviour and the development of appropriate design methods. This article significantly expands the available panel level compressive strength knowledge, demonstrating the strength potential of a welded aircraft panel with multiple lateral and longitudinal stiffener bays. An accompanying computational study has determined the most significant process residual effects that influence panel strength and the potential extent of panel degradation. The experimental results have also been used to validate a previously published design method, suggesting accurate predictions can be made if the conventional aerospace design methods are modified to acknowledge the welding altered panel properties.
A three-dimensional numerical investigation on drag reduction of a supersonic spherical body with an opposing jet
Authors: Zhou ChaoYing , Ji WenYing
Published: December 2012

A three-dimensional numerical simulation of a supersonic free-stream at Mach 2.5 over a spherical body with a sonic opposing jet from its stagnation point is carried out by solving the three-dimensional Navier–Stokes equations coupled with the standard k–ɛ turbulence model. It is aimed to investigate the effects of the jet on the drag reduction on the body and the flow field around the body. The influences of the jet pressure, the nozzle size of the jet, and the angle of attack are systematically studied for the purpose. An unsteady oscillatory motion mode and a nearly steady motion mode are identified depending upon the jet total pressure. There exists a critical jet pressure where the flow mode transition from one to the other happens suddenly and this critical pressure value varies approximately linearly with the jet nozzle exit size inversely. For the zero angle of attack, the results show that there exists a maximum overall drag reduction as the jet pressure changes for each jet nozzle size and the maximum overall drag reduction always happens at the unsteady oscillatory motion mode. The main shock in front of the body is pushed backward by the jet and the displacement of the shock decreases with the increase of the angle of attack, and the drag reduction efficiency also decreases with the angle. Regarding to the mode transition, it is found that the drag rises suddenly when the transition happens for the angle of attack smaller than or equal to 5° but it does not result in the rise for the angle larger than 5°. The results show that the maximum overall drag reduction can be reached as high as 32.6% for the cases studied. The present results provide useful information for drag reduction applications using an opposing jet.
Airflow hazard prediction for helicopter flight in icing condition
Authors: Cao Yihua , Li Guozhi , Sheridan J
Published: December 2012

A methodology to predict the airflow hazard of helicopter flight in icing conditions is developed. By incorporating the existent ice accretion codes into an established basic helicopter flight dynamic model and considering airflow disturbance that mainly covers downdraft, head/tail wind, and left/right wind, the hazardous effects on trims, stability, and controllability of UH-60A single rotor helicopter in icing/ice-free conditions and within/without different types of wind field are investigated. The stability and controllability of helicopter that encounters airflow disturbance from wind velocity of 0 to 2.5–5.0 m/s for forward flight are examined. The indications of all the work are summarized at the end of this article. Furthermore, this method can be used to helicopter inflight safety prediction or airflow hazard avoidance analysis in icing conditions. It can also be laid as the foundation of the further research about the more complex airflow hazard prediction in icing conditions for helicopter flight safety.
Optimal feedback stabilization of a two-axis gimbaled system subject to saturation nonlinearity and multiple disturbances
Authors: Zhan ST , Yan WX , Fu Z , Zhao YZ
Published: December 2012

Disturbances induced from platform motion, gimbal imbalance and state couplings, may severely degrade the line-of-sight tracking accuracy of a two-axis gimbaled system and even induce instability. This article intends to present a stable approach to realize optimal disturbance attenuation for a yaw-pitch gimbaled system, in the presence of saturation nonlinearity and multiple disturbances. A dynamic model of the line-of-sight dynamics is formulated and linearized; feedback controllers are synthesized via linear matrix inequalities and convex optimization; state trajectories of the system before and after stabilization are compared to examine the effectiveness of the feedback approach. The simulation results show that the synthesized controllers are effective in stabilizing the system and realizing optimal disturbance attenuation.
Adjustment and ethno-lingual identification of Kazakh repatriates: Results of sociolinguistic research
Authors: Bokayev Baurzhan , Kazhenova Aigul , Zharkynbekova Sholpan , Beisembayeva Gulshat , Nurgalieva Saniya
Published: December 2012

This article discusses the process of adjustment for repatriates into their country of origin and considers their ethno-lingual identification. This article also presents the results of a sociolinguistic survey among Kazakh repatriates, in particular the questions connected with the influence of language on the process of ethno-lingual identification and the role of language competence in readapting to the country of origin.
Nietzsche’s money
Authors: Dodd Nigel
Published: December 2012

Although Nietzsche rarely features in discussions of money, he offered important insights into such matters as the relationship between the money economy and the permanent decadence of modernity, money’s impact on social hierarchy and individualism and the moral economy of debt. His remarks on these themes are closely connected to two of his best known, but controversial, ideas: the eternal return and the Übermensch. In this paper, I explore how Nietzsche’s arguments, and these two concepts in particular, have been taken up by three thinkers who have made distinctive and original contributions to the sociological and philosophical understanding of money, credit and debt: Georg Simmel in The Philosophy of Money (1907), Walter Benjamin in ‘Capitalism as Religion’ (1921), and Norman Brown in Life Against Death (1959). Nietzsche’s ideas fulfil a pivotal role in each of these treatments of money: in particular, he informs Simmel’s exploration of the relationship between money, individualism and socialism; Benjamin’s examination of the ‘guilt history’ of modern capitalism and its moral economy of debt; and, finally, Brown’s explorations of the roots and consequences of our neurotic money complex. Each of these thinkers puts a different complexion on Nietzsche’s own thoughts regarding money, as well as his broader philosophy. Nevertheless, he provides all three thinkers with a sharply critical perspective on the idea that money’s expansion in the modern world reflects the individual’s liberation from traditional social ties and ancient moral bonds.
Pod Stalinem: Field notes from another modernity
Authors: Sayer Derek
Published: December 2012

David Frisby’s work was a career-long engagement with modernity, informed by a tradition of classical social theory whose neglect in Anglo-American sociology David did much to remedy through his translations as well as his writings: the ‘sociological impressionism’ that seeks to grasp totalities through ‘snapshots’ and ‘fragments’ whose representatives included Georg Simmel, Siegfried Kracauer, and Walter Benjamin. Conceived as a homage to David’s legacy (and his personal influence on my own intellectual development) rather than a commentary on his work, this essay is a Benjaminian dérive through twentieth-century Prague, which complements and counterpoints David’s beloved Vienna and Berlin. Prague’s modern history, I argue, gives Baudelaire’s celebrated definition of modernity as ‘ le transitoire, le fugitif, le contingent’ surreally new dimensions. Indeed, the city might well be regarded as a ‘capital of the twentieth century’ in whose ‘ruins’ we can begin to excavate the ‘prehistory of postmodernity.’
Determining optimal sample sizes for multistage adaptive randomized clinical trials from an industry perspective using value of information methods
Authors: Chen Maggie H , Willan Andrew R
Published: December 2012

Background

 Most often, sample size determinations for randomized clinical trials are based on frequentist approaches that depend on somewhat arbitrarily chosen factors, such as type I and II error probabilities and the smallest clinically important difference. As an alternative, many authors have proposed decision-theoretic (full Bayesian) approaches, often referred to as value of information methods that attempt to determine the sample size that maximizes the difference between the trial’s expected utility and its expected cost, referred to as the expected net gain. Taking an industry perspective, Willan proposes a solution in which the trial’s utility is the increase in expected profit. Furthermore, Willan and Kowgier, taking a societal perspective, show that multistage designs can increase expected net gain.

Purpose

 The purpose of this article is to determine the optimal sample size using value of information methods for industry-based, multistage adaptive randomized clinical trials, and to demonstrate the increase in expected net gain realized. At the end of each stage, the trial’s sponsor must decide between three actions: continue to the next stage, stop the trial and seek regulatory approval, or stop the trial and abandon the drug.

Methods

 A model for expected total profit is proposed that includes consideration of per-patient profit, disease incidence, time horizon, trial duration, market share, and the relationship between trial results and probability of regulatory approval. The proposed method is extended to include multistage designs with a solution provided for a two-stage design. An example is given.

Results

 Significant increases in the expected net gain are realized by using multistage designs.

Limitations

 The complexity of the solutions increases with the number of stages, although far simpler near-optimal solutions exist. The method relies on the central limit theorem, assuming that the sample size is sufficiently large so that the relevant statistics are normally distributed.

Conclusion

 From a value of information perspective, the use of multistage designs in industry trials leads to significant gains in the expected net gain.
Bipolar plasma vaporization versus standard transurethral resection in secondary bladder neck sclerosis: a prospective, medium-term, randomized comparison
Authors: Geavlete Bogdan , Moldoveanu Cristian , Iacoboaie Catalin , Geavlete Petrisor
Published: December 2012

Objectives:

This prospective, randomized, medium-term trial aimed to assess the efficiency, safety and postoperative results of bipolar plasma vaporization (BPV) in comparison with monopolar transurethral resection (TUR) in cases of secondary bladder neck sclerosis (BNS).

Methods:

A total of 70 patients with BNS secondary to transurethral resection of the prostate (TURP; 46 cases), open prostatectomy for benign prostatic hypertrophy (BPH; 18 cases) and radical prostatectomy for prostate cancer (6 cases) were enrolled in the trial. The inclusion criteria consisted of maximum flow rate ( Qmax) <10 ml/s and International Prostate Symptom Score (IPSS) >19. All patients were evaluated preoperatively and at 1, 3, 6, 12 and 18 months after surgery by IPSS, quality of life score (QoL), Qmax and postvoiding residual urinary volume (PVR).

Results:

The mean operation time (10.3 versus 14.9 minutes), catheterization period (0.75 versus 2.1 days) and hospital stay (1.1 versus 3.2 days) were significantly reduced in the BPV series. During the immediate postoperative follow up, recatheterization for acute urinary retention only occurred in the TUR series (5.7%). The medium-term retreatment requirements due to BNS recurrence were lower in the BPV study arm (2.8% versus 8.5%). At the 1, 3, 6, 12 and 18 months assessments, statistically similar parameters were found concerning the IPSS and QoL symptom scores, Qmax and PVR values specific for the two therapeutic alternatives.

Conclusions:

BPV constitutes a valuable endoscopic treatment approach for secondary BNS. The method emphasized superior efficacy, a satisfactory safety profile and similar medium-term follow-up features when compared with standard TUR.
Targeted therapy and immunotherapy in advanced melanoma: an evolving paradigm
Authors: Khattak Muhammad , Fisher Rosalie , Turajlic Samra , Larkin James
Published: December 2012

Metastatic melanoma is one of the most challenging malignancies to treat and often has a poor outcome. Until recently, systemic treatment options were limited, with poor response rates and no survival advantage. However, the treatment of metastatic melanoma has been revolutionized by developments in targeted therapy and immunotherapy; the BRAF inhibitor, vemurafenib, and anticytotoxic T-lymphocyte antigen 4 antibody, ipilimumab, are the first agents to demonstrate a survival benefit. Despite the success of these treatments, most patients eventually progress, and research into response and resistance mechanisms, rationally designed combination therapies and evaluation of the role of these agents in the adjuvant setting is critically important.
Cutaneous Myoepithelioma in the Foot
Authors: Dix Brian T. , Hentges Matthew J. , Saltrick Karl R. , Krishnamurti Uma
Published: December 2012

Cutaneous myoepithelioma is a very rare, benign, subcutaneous and dermal tumor. It usually presents as a slow-growing and painless mass on the extremities. We report a case of cutaneous myoepithelioma that was located on the foot. A 68-yearold woman presented with a slowly growing pain-free mass on the right third toe measuring 0.8 × 0.7 × 0.4 cm3. We performed an elliptical excision, with histological and immunohistochemical analysis. The lesion showed dermis with cords of cytologically uniform ovoid cells with moderate amount of pale cytoplasm. No pleomorphism, mitotic activity, or necrosis was visualized. The tumor cells were positive for S-100 protein, epithelial membrane antigen and negative for smooth-muscle actin. From these findings, the tumor was diagnosed as a cutaneous myoepithelioma extending to the deep resection margin. To our knowledge, there are only 2 documented cases in the literature in English, and none have been reported in the foot and ankle literature.

Levels of Evidence: Therapeutic, Level IV, Case study
Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation
Authors: Haroche Julien , Cohen-Aubart Fleur , Emile Jean-François , Arnaud Laurent , Maksud Philippe , Charlotte Frédéric , Cluzel Philippe , Drier Aurélie , Hervier Baptiste , Benameur Neïla , Besnard Sophie , Donadieu Jean , Amoura Zahir
Published: December 2012

Key Points

Treatment with vemurafenib induced a dramatic response in 3 patients with histiocytosis harboring BRAF V600E mutations. Tumor response was observed in both Erdheim-Chester disease and Langerhans cell histiocytosis.
Parthenolide eliminates leukemia-initiating cell populations and improves survival in xenografts of childhood acute lymphoblastic leukemia
Authors: Diamanti Paraskevi , Cox Charlotte V. , Moppett John P. , Blair Allison
Published: December 2012

Key Points

First report demonstrating in vivo elimination of multiple LIC populations from childhood ALL cases using animal models. In vivo models of leukemia are essential for drug evaluation studies.
HIF-1α is a protective factor in conditional PHD2-deficient mice suffering from severe HIF-2α–induced excessive erythropoiesis
Authors: Franke Kristin , Kalucka Joanna , Mamlouk Soulafa , Singh Rashim Pal , Muschter Antje , Weidemann Alexander , Iyengar Vasuprada , Jahn Steffen , Wieczorek Kathrin , Geiger Kathrin , Muders Michael , Sykes Alex M. , Poitz David M. , Ripich Tatsiana , Otto Teresa , Bergmann Sybille , Breier Georg , Baretton Gustavo , Fong Guo-Hua , Greaves David R. , Bornstein Stefan , Chavakis Triantafyllos , Fandrey Joachim , Gassmann Max , Wielockx Ben
Published: December 2012

Erythropoiesis must be tightly balanced to guarantee adequate oxygen delivery to all tissues in the body. This process relies predominantly on the hormone erythropoietin (EPO) and its transcription factor hypoxia inducible factor (HIF). Accumulating evidence suggests that oxygen-sensitive prolyl hydroxylases (PHDs) are important regulators of this entire system. Here, we describe a novel mouse line with conditional PHD2 inactivation (cKO P2) in renal EPO producing cells, neurons, and astrocytes that displayed excessive erythrocytosis because of severe overproduction of EPO, exclusively driven by HIF-2α. In contrast, HIF-1α served as a protective factor, ensuring survival of cKO P2 mice with HCT values up to 86%. Using different genetic approaches, we show that simultaneous inactivation of PHD2 and HIF-1α resulted in a drastic PHD3 reduction with consequent overexpression of HIF-2α-related genes, neurodegeneration, and lethality. Taken together, our results demonstrate for the first time that conditional loss of PHD2 in mice leads to HIF-2α–dependent erythrocytosis, whereas HIF-1α protects these mice, providing a platform for developing new treatments of EPO-related disorders, such as anemia.
Hemolysis and free hemoglobin revisited: exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins
Authors: Schaer Dominik J. , Buehler Paul W. , Alayash Abdu I. , Belcher John D. , Vercellotti Gregory M.
Published: December 2012

Hemolysis occurs in many hematologic and nonhematologic diseases. Extracellular hemoglobin (Hb) has been found to trigger specific pathophysiologies that are associated with adverse clinical outcomes in patients with hemolysis, such as acute and chronic vascular disease, inflammation, thrombosis, and renal impairment. Among the molecular characteristics of extracellular Hb, translocation of the molecule into the extravascular space, oxidative and nitric oxide reactions, hemin release, and molecular signaling effects of hemin appear to be the most critical. Limited clinical experience with a plasma-derived haptoglobin (Hp) product in Japan and more recent preclinical animal studies suggest that the natural Hb and the hemin-scavenger proteins Hp and hemopexin have a strong potential to neutralize the adverse physiologic effects of Hb and hemin. This includes conditions that are as diverse as RBC transfusion, sickle cell disease, sepsis, and extracorporeal circulation. This perspective reviews the principal mechanisms of Hb and hemin toxicity in different disease states, updates how the natural scavengers efficiently control these toxic moieties, and explores critical issues in the development of human plasma–derived Hp and hemopexin as therapeutics for patients with excessive intravascular hemolysis.
Chest computed tomography: a validated surrogate endpoint of cystic fibrosis lung disease?
Authors: Loeve Martine , Krestin Gabriel P. , Rosenfeld Margaret , de Bruijne Marleen , Stick Stephen M. , Tiddens Harm A.
Published: December 2012

Clinical trials for the treatment of cystic fibrosis (CF) lung disease are important to test and optimise new therapeutic interventions. To evaluate the effect of these interventions, sensitive and accurate outcome measures are needed. The most commonly used endpoints are spirometric variables such as the forced expiratory volume in 1 s and respiratory tract exacerbations. Unfortunately, these endpoints are relatively insensitive for monitoring progression of CF lung disease, and thus require a large number of patients when used in clinical studies. In addition, these endpoints are not suitable to study CF lung disease in young children. Chest computed tomography (CT) holds great promise for use as a sensitive surrogate endpoint in CF. A large body of evidence has been produced to validate the use of chest CT as a primary endpoint to study CF lung disease. However, before chest CT can be used in clinical trials, it has to be recognised as a validated surrogate endpoint by regulatory agencies. The aim of this review is to summarise what is currently known about the use of chest CT as surrogate endpoint in clinical trials in CF.
Cellular microparticles in the pathogenesis of pulmonary hypertension
Authors: Amabile Nicolas , Guignabert Christophe , Montani David , Yeghiazarians Yerem , Boulanger Chantal M. , Humbert Marc
Published: December 2012

Pulmonary hypertension (PH) is a fatal disease with no treatment options, characterised by elevated pulmonary vascular resistanzce and secondary right ventricular failure. The aetiology of pulmonary arterial hypertension is multiple and its pathogenesis is complex. Although the exact role of cellular microparticles remains partially understood, there is increasing evidence to suggest an active role for microparticles in PH pathophysiology. Patients with PH exhibited higher circulating levels of microparticles compared to control subjects andin vitroorin vivogenerated microparticles can induce endothelial dysfunction, interfere with coagulation pathways or modulate inflammatory phenomenon. Whether or not these new conveyors of biological information contribute to the acquisition and/or maintenance of the altered endothelial phenotype is unexplored in PH and requires further study.
Echocardiography and pulmonary embolism severity index have independent prognostic roles in pulmonary embolism
Authors: Sanchez Olivier , Trinquart Ludovic , Planquette Benjamin , Couturaud Francis , Verschuren Franck , Caille Vincent , Meneveau Nicolas , Pacouret Gérard , Roy Pierre-Marie , Righini Marc , Perrier Arnaud , Bertoletti Laurent , Parent Florence , Lorut Christine , Meyer Guy
Published: December 2012

We analysed a cohort of patients with normotensive pulmonary embolism (PE) in order to assess whether combining echocardiography and biomarkers with the pulmonary embolism severity index (PESI) improves the risk stratification in comparison to the PESI alone.

The PESI was calculated in normotensive patients with PE who also underwent echocardiography and assays of cardiac troponin I and brain natriuretic peptide. 30-day adverse outcome was defined as death, recurrent PE or shock.

529 patients were included, 25 (4.7%, 95% CI 3.2–6.9%) had at least one outcome event. The proportion of patients with adverse events increased from 2.1% in PESI class I–II to 8.4% in PESI class III–IV, and to 14.3% in PESI class V (p<0.001). In PESI class I–II, the rate of outcome events was significantly higher in patients with abnormal values of biomarkers or right ventricular dilatation. In multivariate analysis, the PESI (class III–IVversusI–II, OR 3.1, 95% CI 1.2–8.3; class VversusI–II, OR 5.5, 95% CI 1.5–25.5 and echocardiography (right ventricular/left ventricular ratio, OR (for an increase of 0.1) 1.3, 95% CI 1.1–1.5) were independent predictors of an adverse outcome.

In patients with normotensive PE, biomarkers and echocardiography provided additional prognostic information to the PESI.
Hypereosinophilic obliterative bronchiolitis: a distinct, unrecognised syndrome
Authors: Cordier Jean-François , Cottin Vincent , Khouatra Chahéra , Revel Didier , Proust Clément , Freymond Nathalie , Thivolet-Béjui Françoise , Glérant Jean-Charles
Published: December 2012

Biopsy-proven cases of eosinophilic bronchiolitis have only been reported in isolation, and all come from Japan.

We present six patients with hypereosinophilic obliterative bronchiolitis (HOB), defined by the following criteria: 1) blood eosinophil cell count >1 G·L−1and/or bronchoalveolar lavage eosinophil count >25%; 2) persistent airflow obstruction despite high-dose inhaled bronchodilators and corticosteroids; and 3) eosinophilic bronchiolitis at lung biopsy (n=1) and/or direct signs of bronchiolitis (centrilobular nodules and branching opacities) on computed tomography (n=6).

Chronic dyspnoea and cough which was often severe, without the characteristic features of asthma, were the main clinical manifestations. Atopy and asthma were present in the history of three and two patients, respectively. One patient met biological criteria of the lymphoid variant of idiopathic hypereosinophilic syndrome. Mean blood eosinophil cell count was 2.7 G·L−1and mean eosinophil differential percentage at bronchoalveolar lavage was 63%. Mean initial forced expiratory volume in 1 s/forced vital capacity ratio was 50%, normalising with oral corticosteroid therapy in all patients. HOB manifestations recurred when oral prednisone was decreased to 10–20 mg·day−1, but higher doses controlled the disease.

HOB is a characteristic entity deserving to be individualised among the eosinophilic respiratory disorders. Thorough analysis is needed to determine whether unrecognised and/or smouldering HOB may further be a cause of irreversible airflow obstruction in chronic eosinophilic respiratory diseases.
Respiratory muscle function in interstitial lung disease
Authors: Walterspacher Stephan , Schlager Daniel , Walker David J. , Müller-Quernheim Joachim , Windisch Wolfram , Kabitz Hans-Joachim
Published: December 2012

Interstitial lung diseases limit daily activities, impair quality of life and result in (exertional) dyspnoea. This has mainly been attributed to a decline in lung function and impaired gas exchange. However, the contribution of respiratory muscle dysfunction to these limitations remains to be conclusively investigated.

Interstitial lung disease patients and matched controls performed body plethysmography, a standardised 6-min walk test, volitional tests (respiratory drive (P0.1), global maximal inspiratory mouth occlusion pressure (PImax), sniff nasal pressure (SnPna) and inspiratory muscle load) and nonvolitional tests on respiratory muscle function and strength (twitch mouth and transdiaphragmatic pressure during bilateral magnetic phrenic nerve stimulation (TwPmoand TwPdi)).

25 patients and 24 controls were included in the study.PImaxand SnPnaremained unaltered (both p>0.05), whereasP0.1and the load on the inspiratory muscles were higher (both p<0.05) in interstitial lung disease patients compared with controls. TwPmoand TwPdiwere lower in interstitial lung disease patients (mean±sdTwPmo0.86±0.4versus1.32±0.4, p<0.001; TwPdi1.34±0.6versus1.88±0.5, p=0.022).

Diaphragmatic force generation seems to be impaired in this cohort of interstitial lung disease patients while global respiratory muscle strength remains preserved. Central respiratory drive and the load imposed on the inspiratory muscles are increased. Whether impaired respiratory muscle function impacts morbidity and mortality in interstitial lung disease patients needs to be investigated in future studies.
Comparisons of health status scores with MRC grades in COPD: implications for the GOLD 2011 classification
Authors: Jones Paul W. , Adamek Lukasz , Nadeau Gilbert , Banik Norbert
Published: December 2012

The 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy document recommends assessment of chronic obstructive pulmonary disease (COPD) using symptoms and future exacerbation risk, employing two score cut-points: COPD Assessment Test (CAT) score ≥10 or modified Medical Research Council dyspnoea scale (mMRC) grade ≥2. To explore the equivalence of these two symptom cut-points, the relationship between the CAT and the mMRC and St George's Respiratory Questionnaire (SGRQ), the Short-form Health Survey and the Functional Assessment of Chronic Illness Therapy Fatigue scores were retrospectively analysed using a primary care dataset.

Data from 1817 patients (mean±sdforced expiratory volume in 1 s 1.6±0.6 L) showed a significant association between mMRC grades and all health status scores (ANOVA p<0.0001). mMRC grade 1 was associated with significant levels of health status impairment (SGRQ 39.4±15.5 and CAT 15.7±7.0); even patients with mMRC grade 0 had modestly elevated scores (SGRQ 28.5±15.1 and CAT 11.7±6.8). An mMRC grading ≥2 categorised 57.2% patients with low symptom (groups A and C)versus17.2% with the CAT. Using the mMRC cut-point (≥1) resulted in similar GOLD group categorisations as the CAT (18.9%).

The mMRC showed a clear relationship with health status scores; even low mMRC grades were associated with health status impairment. Cut-points of mMRC grade ≥1 and CAT score ≥10 were approximately equivalent in determining low-symptom patients. The GOLD assessment framework may require refinement.