bluuebunny/crossref_metadata_2025 huggingface dataset:
Varieties of corporate networks: Network analysis and fsQCA
Authors: Cárdenas Julián
Published: November 2012

The present research analyzes national corporate interlock networks and their causal conditions. The objective is two-fold: 1) to specify types of corporate networks, and 2) to pinpoint the causal configurations that give rise to each type of corporate network. First, corporate networks on basis of interlocking directorates are analyzed and compared using social network analysis to empirically derive a typology. The results show two types of corporate networks: cohesive corporate networks which are based on unification, centralization and strength ties; and dispersed corporate networks which are characterized by fragmentation, decentralization and single ties. Second, combinations of causal conditions that explain the emergence of each type of corporate networks are identified using fuzzy set qualitative comparative analysis (fsQCA). Finally, avenues of research on corporate interlock networks are suggested.
Shear Mechanics of the TMJ Disc
Authors: Juran C.M. , Dolwick M.F. , McFetridge P.S.
Published: November 2012

The temporomandibular joint (TMJ) is a complex hinge and gliding joint that induces significant shear loads onto the fibrocartilage TMJ disc during jaw motion. The purpose of this study was to assess regional variation in the disc’s shear loading characteristics under physiologically relevant loads and to associate those mechanical findings with common clinical observations of disc fatigue and damage. Porcine TMJ discs were compressed between an axially translating bottom platen and a 2.5-cm-diameter indenter within a hydrated testing chamber. Discs were cyclically sheared at 0.5, 1, or 5 Hz to 1, 3, or 5% shear strain. Within the anterior and intermediate regions of the disc when sheared in the anteroposterior direction, both shear and compressive moduli experienced a significant decrease from instantaneous to steady state, while the posterior region’s compressive modulus decreased approximately 5%, and no significant loss of shear modulus was noted. All regions retained their shear modulus within 0.5% of instantaneous values when shear was applied in the mediolateral direction. The results of the disc’s regional shear mechanics suggest an observable and predictable link with the common clinical observation that the posterior region of the disc is most often the zone in which fatigue occurs, which may lead to disc damage and perforation.
The duration and durability of cabinet ministers
Authors: Fischer Jörn , Dowding Keith , Dumont Patrick
Published: November 2012

This article surveys the growing research programme on the duration of cabinet ministers. It examines some of the conceptual and methodological issues confronting research, including the nature and measurement of durability, ministerial terms and techniques. It considers some of the theories and hypotheses that have been generated by researchers. Using evidence from studies from around the world, it argues that institutional factors, including regime type, constitutional and parliamentary rules, and party systems, affect ministerial durability. Personal ministerial characteristics, such as gender, education and age, also affect durability. It examines future avenues of research in this field.
The Governmentality of Battlefield Space
Authors: Kontour Kyle
Published: November 2012

With the rise of the so-called military-entertainment complex, critical scholars note with alarm the integration of the political economies of entertainment companies and the military, in particular its potential influence on millions of young people who consume its concomitant films, toys and especially video games. Seen from a broad perspective, a potentially productive means of understanding the complexities of this sphere is through the lens of Michel Foucault’s notion of governmentality—a concept that ties together the actions and preferred outcomes of the modern surveillance state with the microlevel actions of individual behavior. In this analytical framework, social norms are inculcated through subtle forms of coercion, where the state establishes the field of action in which state subjects ultimately perform self-discipline. This article argues that the first person shooter genre inculcates what I refer to as the governmentality of battlefield space: a form of discipline in which players adhere to gamic norms of performance—efficiency, proficiency, and masculine performativity—which are delineated by ludic structures and largely understood on terms which originate within the social ecology of gaming. The genre accomplishes this though disciplinary techniques such as informational verisimilitude, statistics, and masculinized “gamer” discourse, particularly during multiplayer instances, in which players constitute social understandings of what is “good” and “bad” play. It is on these terms that virtual combat performance and player performance become conflated in a kind of masculinized performance, which both adheres to and undermines traditional, hegemonic norms of (Western) military masculinity. This phenomenon transcends local social realities, and highlights the ways in which particular aspects of gaming and combat appear to have increasingly overlapping phenomenological and ontological qualities, working to produce a form of self-performance that may be required of tomorrow’s soldiers.
“Sure, I Would Like to Continue”
Authors: Schønau-Fog Henrik , Bjørner Thomas
Published: November 2012

In order to explore one aspect of the engaging nature of computer games, this study will propose a method that aims at classifying the experience of engagement in video games. Inspired by a literature review, we will focus on the fundamental causes of engagement that motivate a player so much that he or she wants to continue playing. By organizing this willingness to continue playing into six broad types of causes of engagement—intellectual, physical, sensory, social, narrative, and emotional—we describe a typology of player engagement and a method that is intended to map players’ experience of engagement while playing video games. The engagement mapping method is inspired by card sorting found from a perspective of usability testing, and in order to exemplify the use of the method, occurrences of the six types of engagement were investigated during gameplay in Angry Birds and Wii Sports.
Randomized, double-blind, placebo-controlled, phase II trial of gabapentin enacarbil for migraine prophylaxis
Authors: Silberstein Stephen , Goode-Sellers Stacey , Twomey Colleen , Saiers Jane , Ascher John
Published: November 2012

Objective

The objective of this article is to evaluate the efficacy and safety of gabapentin enacarbil (GEn) for migraine prophylaxis.

Methods

In this randomized, double-blind, parallel-group study, patients with International Headache Society-defined migraine who met criteria suggesting the need for prophylactic therapy were randomized 2:1:2:2:1 to one of the following five groups, designated according to target daily dose of study medication during the 20-week treatment period: placebo, GEn 1200 mg, GEn 1800 mg, GEn 2400 mg, or GEn 3000 mg.

Results

The intent-to-treat population included 523 patients ( n = 128 placebo, n = 66 GEn 1200 mg, n = 134 GEn 1800 mg, n = 133 GEn 2400 mg, n = 62 GEn 3000 mg). No statistically significant difference between active treatment (the average of 1800 mg and 2400 mg treatment groups) and placebo was found for change from baseline in the number of migraine headache days during the last four weeks of treatment prior to taper (the primary endpoint). Results of analyses of the primary endpoint using the per protocol population, analyses using imputation methods different from those of the primary analysis, and nonparametric analyses were consistent with the primary analysis in showing no difference between active treatment and placebo. The pattern of results was similar for the secondary efficacy endpoints. Pharmacokinetic data demonstrate that patients had adequate estimated exposure to GEn. The adverse event profile of GEn was consistent with that in previous studies.

Conclusion

GEn did not significantly differ from placebo for migraine headache prophylaxis. A high placebo effect should be considered when interpreting these results.
Nepalese diasporic websites: Signs and conditions of a diaspora in the making?
Authors: Bruslé Tristan
Published: November 2012

Since the beginning of the 21st century, the expression ‘Nepalese diaspora’ has increasingly been used by the Nepalese government, expatriates, reporters and intellectuals. The Nepalese diaspora, or those who speak on behalf of it, occupies a growing amount of Nepalese public space, especially on the Internet. Taking into account the performativity of the term ‘diaspora’, the author tries to understand how Nepalese diasporic websites are the sign and conditions of an ‘incipient diaspora’. Analysis of authoritative websites and links between different websites helps understand the structure of the Nepalese diaspora and the issues at stake. The Internet is hardly egalitarian and reflects the tensions in Nepalese society. However, links between websites are real. Non-Resident Nepalis’ Association websites are central to the associative Web, and cultural association websites are in the majority. The ‘etic’ study of ‘emic’ discourses of self-presentation by the diaspora shows that, through their public and performative dimensions, Nepalese diasporic websites are at the very heart of the process of constructing the Nepalese diaspora.
Are Anti-LGBT Homicides in the United States Unique?
Authors: Gruenewald Jeff
Published: November 2012

An integral issue to the study of bias crimes is how violence targeting lesbian, gay, bisexual, and transgender (LGBT) victims is different from other more common forms of violent crimes. Limitations in official bias crimes data have inhibited our understanding of the relative nature of anti-LGBT crimes. The purpose of this study is to examine the similarities and differences in anti-LGBT homicides and average homicides in the United States between 1990 and 2008. The current study addresses methodological issues by relying on an open-source database of anti-LGBT homicides. This study found that the nature of these homicides is both similar and significantly different from the average homicide. Implications for the ongoing bias crimes discourse are discussed.
Educating the Spirit of Activism
Authors: Wheeler-Bell Quentin
Published: November 2012

Often when philosophers of education address the issue of civic education, they focus on the characteristics individuals should possess to participate in the preexisting democracy; these skills include the ability to listen carefully, reasonably reflect and weigh evidence, articulate one’s demands and concerns in the public sphere, and so forth. However, little consideration is given to the type of collective sensibility necessary to move toward the more ideal society. This article aims to broaden our conception of civic education by detailing the type of citizen that is necessary to create and maintain an ideal society—a deep socialist democracy.
Designing and testing an advanced pneumatic braking system for heavy vehicles
Authors: Miller Jonathan I , Henderson Leon M , Cebon David
Published: November 2012

Heavy goods vehicles exhibit poor braking performance in emergency situations when compared to other vehicles. Part of the problem is caused by sluggish pneumatic brake actuators, which limit the control bandwidth of their antilock braking systems. In addition, heuristic control algorithms are used that do not achieve the maximum braking force throughout the stop. In this article, a novel braking system is introduced for pneumatically braked heavy goods vehicles. The conventional brake actuators are improved by placing high-bandwidth, binary-actuated valves directly on the brake chambers. A made-for-purpose valve is described. It achieves a switching delay of 3–4 ms in tests, which is an order of magnitude faster than solenoids in conventional anti-lock braking systems. The heuristic braking control algorithms are replaced with a wheel slip regulator based on sliding mode control. The combined actuator and slip controller are shown to reduce stopping distances on smooth and rough, high friction ( μ = 0.9) surfaces by 10% and 27% respectively in hardware-in-the-loop tests compared with conventional ABS. On smooth and rough, low friction ( μ = 0.2) surfaces, stopping distances are reduced by 23% and 25%, respectively. Moreover, the overall air reservoir size required on a heavy goods vehicle is governed by its air usage during an anti-lock braking stop on a low friction, smooth surface. The 37% reduction in air usage observed in hardware-in-the-loop tests on this surface therefore represents the potential reduction in reservoir size that could be achieved by the new system.
Investigations on the viscoelastic behaviour of a human healthy heel pad: In vivo compression tests and numerical analysis
Authors: Matteoli Sara , Fontanella Chiara G , Carniel Emanuele L , Wilhjelm Jens E , Virga Antonio , Corbin Nadège , Corvi Andrea , Natali Arturo N
Published: November 2012

The aim of this study was to investigate the viscoelastic behaviour of the human heel pad by comparing the stress–relaxation curves obtained from a compression device used on an in vivo heel pad with those obtained from a three-dimensional computer-based subject-specific heel pad model subjected to external compression. The three-dimensional model was based on the anatomy revealed by magnetic resonance imaging of a 31-year-old healthy female. The calcaneal fat pad tissue was described with a viscohyperelastic model, while a fibre-reinforced hyperelastic model was formulated for the skin. All numerical analyses were performed to interpret the mechanical response of heel tissues, with loading conditions and displacement rate in agreement with experimental tests. The heel tissues showed a non-linear, viscoelastic behaviour described by characteristic hysteretic curves, stress–relaxation and viscous recovery phenomena. The reliability of the investigations was validated by the interpretation of the mechanical response of heel tissues under the application of three pistons with diameter of 15, 20 and 40 mm, at the same displacement rate of about 1.7 mm/s. The maximum and minimum relative errors were found to be less than 0.95 and 0.064, respectively.
The eastern Australian magnetic inclination record: Dating the recent past and re-assessing the historical geomagnetic archive
Authors: Gale SJ , Cook DE , Dorrington NJ
Published: November 2012

A new compilation of historical observations and archaeomagnetic measurements of magnetic inclination for the last 1000 years from eastern Australia (the eastern Australian Inclination Record [ eAIR2012]) has revealed the existence of a well-defined inclination anomaly in the region. Evidence of this magnetic feature has been preserved in sedimentary records from across eastern Australia, though this has not previously been recognised. Analyses of additional sedimentary sequences have confirmed the incidence and timing of this feature, revealing its presence between the 13th and 18th centuries ad. The inclination of the field during this episode appears to have been steeper than at any time since the start of the Holocene. Lake sediment evidence suggests that the anomaly is a composite feature, displaying a distinct peak at cal. ad 1270–1386 (±2 σ uncertainty), reappearing after cal. ad 1431–1651 (±2 σ uncertainty) and disappearing before cal. ad 1822±46 (±2 σ uncertainty). The disappearance of the anomaly is tightly bracketed in the historical record between ad 1770 and 1777. The rapid shift in inclination during the 18th century ad offers considerable potential as a means of dating a critical period of Australian environmental history, an episode that currently lies beyond the reach of established dating methods. This information also provides a valuable constraint on models of regional geomagnetic field change over centennial and millennial timescales. Our examination of the historical record has revealed that the inclination measurements made by the 18th-century French explorer La Pérouse are consistently erroneous. Since La Pérouse’s data make up 13% of the total body of pre-19th century inclination records, the inclusion of these measurements in global compendia of magnetic observations may seriously skew attempts to model the geomagnetic field. We advocate that La Pérouse’s inclination measurements should therefore be employed only with considerable caution.
Patterns of Alcohol and Tobacco Use in Cambodia
Authors: Banta Jim E. , Addison Askari , Job Jayakaran S. , Yel Daravuth , Kheam They , Singh Pramil N.
Published: November 2012

Few studies have considered whether the habitual use of tobacco in Southeast Asia is part of an established pattern of addiction that includes regular alcohol use. As part of a national survey of adult tobacco use in Cambodia (n = 13 988), we found that men who smoked were 2 times more likely to have drank alcohol in the past week (odds ratio = 2.53, 95% confidence interval = 2.10-3.03). By age 18 to 25 years, 47% of male smokers drank alcohol, and this pattern of alcohol and tobacco use increased to >55% through the fifth decade. Women using smokeless tobacco with betel quid were more likely to be alcohol drinkers (odds ratio = 1.49, 95% confidence interval = 1.12-1.98). Past week’s drinking declined by late middle age and was associated with lower education and being currently married; the behavior was lower in some ethnic groups (ie, Cham). Our findings indicate an important association between alcohol and tobacco use, and raise the possibility that reducing alcohol consumption can be an important component of tobacco control.
Value of histopathology, immunohistochemistry, and real-time polymerase chain reaction in the confirmatory diagnosis of Encephalitozoon cuniculi infection in rabbits
Authors: Leipig Miriam , Matiasek Kaspar , Rinder Heinz , Janik Dirk , Emrich Daniela , Baiker Kerstin , Hermanns Walter
Published: November 2012

Morphological lesions in kidneys and brain are all too often considered diagnostic for confirmation of encephalitozoonosis in rabbits. The current study evaluated the diagnostic value of histology versus other etiological tests, including immunohistochemistry and real-time polymerase chain reaction (PCR) for Encephalitozoon cuniculi infection diagnosis. Samples of brain, heart, lungs, intestine, liver, and kidneys from 81 rabbits were examined for morphological lesions attributed to E. cuniculi infection as well as for the presence of spores and E. cuniculi antigen. Of these, 55 rabbits were tested for E. cuniculi DNA. Histological changes consistent with E. cuniculi infection were seen in 33 rabbits (41%, 33/81) representing 87% (33/38) of all rabbits with confirmed E. cuniculi infection. Brains of these rabbits displayed 6 different types of focal lesions corresponding to the stage of infection and specific tissue response. In 5 rabbits that were tested positive, histology was either inconclusive or inconspicuous. Etiological diagnosis was based on histological spore detection in 16% (6/38) of infected rabbits. Immunohistochemistry was more sensitive (42%, 16/38) than histological spore detection, and real-time PCR proved to be the most sensitive of all investigated methods (30/35, 86% of the examined rabbits with E. cuniculi infection). Encephalitozoon cuniculi infection rarely occurs without characteristic kidney and brain lesions. However, the spectrum of brain changes is wider than previously reported. Based on these findings, confirmation of pathogenic E. cuniculi infection should include standard histology of the predilection sites and a specific etiological assay, preferably real-time PCR.
A case of umbilical cord teratoma in an aborted foal
Authors: Binanti Diana , Livini Marco , Riccaboni Pietro , Sironi Giuseppe
Published: November 2012

A 16-year-old primiparous mare aborted an apparently normal fetus at 240 days of gestation. A large, oval mass, measuring approximately 20 cm × 30 cm × 20 cm, was detected attached to the umbilical cord of the fetus. On the cut surface, the mass showed multifocal cystic structures, foci of mineralization, and diffuse hemorrhages. Histological examination of the mass revealed haphazardly arranged cartilage, bone, mesenchymal stroma, adipose tissue, vascular structures, smooth muscle, ciliated epithelium, squamous cornifying epithelium, and undifferentiated germ cells with areas of necrosis and mineralization. The mass was diagnosed as an umbilical cord teratoma, which is an extremely rare tumor in human beings and, to the authors’ knowledge, has only described in the veterinary literature on one occasion.
Integrating nondestructive inspections with autonomic logistics and structural health monitoring strategies for aeronautic systems
Authors: Gyekenyesi Andrew
Published: November 2012

In recent years, there has been much activity concerning health management of aviation systems. Many government- and industry-based research projects/programs are focused on integrated vehicle health management strategies that include sensor development for automated or manual fault detection, diagnostics, prognostics to define remaining useful life, as well as mitigation plans for continued safe operation during a fault. The overall objectives for such activities include increased safety as well as efficient and economic operation of an aircraft fleet. Currently, to assess structural faults, visual inspections and/or nondestructive inspection techniques are utilized as a required routine for certain design and life management strategies. The inspections are manually involved and are carried out during aircraft downtime (e.g. on the runway or nightly hangar maintenance) or during a more extensive aircraft overhaul. Even with the potential of automated structural health monitoring within an integrated vehicle health management system, it is foreseen that manual and nondestructive inspections will continue to be an integral part of fleet life management. This article addresses and clarifies the role of nondestructive inspections in aircraft life management and its potential inclusion in future integrated vehicle health management systems.
Data-driven journalism and the public good: “Computer-assisted-reporters” and “programmer-journalists” in Chicago
Authors: Parasie Sylvain , Dagiral Eric
Published: November 2012

Since the mid-2000s, some US and British news organizations have hired programmers to design data-driven news projects within the newsroom. But how does the rise of these “programmer-journalists,” armed with their skills and technical artifacts, really affect the way journalism can contribute to the public good? Based on an empirical study in Chicago, we show in this article that although they have built on previous historical developments, these programmer-journalists have also partly challenged the epistemology conveyed by the computer-assisted reporting tradition in the US, grounded in the assumption that data can help journalists to set the political agenda through the disclosure of public issues. Involved in open source communities and open government advocacy, these programmers and their technical artifacts have conveyed challenging epistemological propositions that have been highly controversial in the journalism community.
Schema-Focused Therapy for Major Depressive Disorder and Personality Disorder
Authors: Seavey Amanda , Moore Todd M.
Published: November 2012

This is a single case study of a college age male with major depressive disorder and personality disorder not otherwise specified (NOS). The patient endorsed feelings of sadness, worthlessness, inattention, isolation, and suicidal and homicidal ideation. In addition, the patient endorsed inflexible and pervasive behavioral patterns such as paranoia, isolation, and narcissism. Treatment consisted of schema therapy, with an emphasis on the therapeutic relationship (limited reparenting). The patient completed Young’s Schema Questionnaire (YSQ) prior to initiating treatment and again following treatment. Schemas endorsed at moderate to high levels include Failure, Enmeshment, Abandonment, Emotional Deprivation, Punitiveness, Negativity/Pessimism, and Social Isolation. Following 68 weeks of schema therapy, the patient endorsed all 18 schemas at a “low” level. In addition, whether these findings demonstrated clinically significant change was examined. Results indicate that four out of seven of the patient’s endorsed schemas demonstrated clinically significant change (Emotional Deprivation, Punitiveness, Negativity/Pessimism, and Social Isolation).
A Pharmacological/Physiological Comparison of Metformin and Exercise
Authors: Lenz Thomas L. , Seyer Matthew R.
Published: November 2012

Type 2 diabetes is a significant health concern in the United States and its prevalence is expected to triple by 2050. Both metformin and exercise have shown to be effective in the management of blood glucose control. The pharmacological mechanism of action of metformin is largely based on the activation of AMPK to induce glucose transport. Likewise, the physiological actions of exercise appear to be a potent activator of AMPK, resulting in glucose uptake by the muscle. Research shows that metformin may control blood glucose slightly better than exercise in persons with type 2 diabetes. However, it appears that lifestyle interventions outperform metformin when trying to prevent the onset of diabetes. Both metformin and exercise have a positive and significant role in the management of type 2 diabetes and appear to work similarly to help manage blood glucose control.
Presentation and impact of market-driven journalism on sensationalism in global TV news
Authors: Wang Tai-Li
Published: November 2012

This study conducted a cross-national television news content analysis in 14 countries to compare the elements of sensationalism appearing in four types of media systems. A secondary analysis was further employed to examine the relationship between news sensationalization, news competition levels, and professionalism of these countries. Results reveal that crime-, accident-, and disaster-related news remain the staples of sensational news across countries. Dual broadcasting systems devoted more sensational news coverage than commercial broadcasting systems. Sensational formal features were found to be limited in all broadcasting systems. Celebrities and ordinary people tended to pose as news actors to personalize and dramatize the news more frequently than allowing officials or authoritative sources to legitimate the stories. Furthermore, news competition has been confirmed as an impact to the boom of news sensationalization. More professional journalists report more soft news than less professional ones.
Selective detection of endotoxin using an impedance aptasensor with electrochemically deposited gold nanoparticles
Authors: Su Wenqiong , Kim Sung-Eun , Cho MiSuk , Nam Jae-Do , Choe Woo-Seok , Lee Youngkwan
Published: November 2012

Using a single-stranded DNA (ssDNA) aptamer exhibiting high binding affinity (Kd = 12 nM) to endotoxin as a probe, an impedance sensor where aptamer-conjugated gold nanoparticles (AuNPs) were electrochemically deposited on a gold electrode was fabricated and its performance in regard to endotoxin detection assessed. AuNPs have been employed widely as biosensors because of their unique physical and chemical properties. In order to maximize the performance of the impedance aptasensor on endotoxin detection, some critical factors affecting aptamer conjugation to AuNPs and target recognition ability (i.e. concentrations of aptamer coupled with AuNPs, pH, ion strength and cation effect at the time of aptamer–endotoxin interaction) were optimized. Electrochemical impendence spectroscopy, cyclic voltametry, atomic force microscope, scanning electron microscope and quartz crystal microbalance were employed to characterize all the modification/detection procedures during the sensor fabrication. The developed aptasensor showed a broad linear dynamic detection range (0.01–10.24 ng/ml) with a very low detection limit for endotoxin (0.005 ng/ml), despite the presence of several biomolecules (e.g. plasmid DNA, RNA, serum albumin, Glc and sucrose) known to interfere with other endotoxin assays. The demonstrated aptasensor required a detection time of only 10 min, providing a simple and fast analytical method to specifically detect endotoxin from complex biological liqors.
Effect of Subject Restraint and Resistance Pad Placement on Isokinetic Knee Flexor and Extensor Strength
Authors: Otten Roald , Whiteley Rod , Mitchell Tim
Published: November 2012

Background:

In clinical practice, several subject restraint and resistance pad placement variations are used when an isokinetic knee flexion/extension test is performed. However, it is unknown if these variations affect the outcome measures. The aims of this study were to determine if these setup variations affect isokinetic outcomes and to establish the smallest detectable difference for these setup variations.

Hypothesis:

Variation in isokinetic setup affects outcome measures.

Study Design:

Cross-sectional repeated-measures crossover study.

Methods:

Ten recreationally active adult men were examined with isokinetic dynamometry on 4 separate days. In the first 3 days, fully strapped and trunk-unstrapped testing was conducted with the resistance pad placed distally on the shin. On days 1 and 3, the unstrapped condition was performed first, followed by the strapped condition. On day 4, the resistance pad was placed proximal on the shin (anterior cruciate ligament testing).

Results:

There were no within-condition differences for days 1, 2, or 3 for the strapped and unstrapped conditions ( P > 0.05). Between-condition comparisons were significant (eg, quadriceps peak torque, P < 0.001; hamstring peak torque, P = 0.043) for the strapped, unstrapped, and proximal resistance pad placement conditions. The strapped condition generally showed the largest torques, and the unstrapped, the least. The smallest detectable differences were relatively large (eg, quadriceps peak torque strapped = 20.6%). The greatest intraclass correlation values were found when strapped.

Conclusions:

Subject setup significantly influences isokinetic outcome measures at the knee. Since the strapped condition demonstrated the greatest repeatability, it is recommended. The smallest detectable differences were relatively high for all variables and should be considered in the interpretation of the effect size of interventions.

Clinical Relevance:

Subject setup strapping must be considered when investigating test-retest values or when comparing subjects after isokinetic testing at the knee. The fully strapped condition has the best repeatability and highest torque values.
Emergency Preparedness
Authors: Flaherty Elizabeth A.
Published: November 2012

Nurses are trained to think in terms of the nursing process, which encompasses the five steps of assessment, diagnosis, outcomes/planning, implementation, and evaluation. Cities and towns have developed emergency plans based on the “all-hazards” approach. School district plans are also formulated based on the all-hazards approach of hazard mitigation, preparedness, response, and recovery, which mirrors the nursing process. Individual school efforts focus on these four principles to facilitate development of a comprehensive plan for each school. Utilizing the principles of education, collaboration, resource utilization, leadership, and advocacy throughout the evolution of an updated and functional plan allows for an inclusive and adaptable plan. Like the nursing process, these steps are not separate and distinct, but a continuous process.
“We Are Against Islam!”
Authors: Testa Alberto , Armstrong Gary
Published: November 2012

Since 1995, the Italian Lega Nord (LN) political party has depicted itself as the defender of Padania, a territory that covers the mainly affluent regions of Northern Italy. Around this politico-spatial territory, the LN has shaped an identity based on the notion of Popolo Padano (the Padanian People). Since the new millennium, LN rhetoric has increasingly focused—stemming more from the demands of realpolitik than those of conviction—on opposing irregular immigration per se and, more specifically, Islam and Muslim immigration. In the eyes of the LN propagandists and their media, the theology of Islam and its practitioners represent a growing threat to the modern Italian and Padanian identity (and tradition). The LN has not been alone in using the media to oppose Islam; the Italian media has reinforced LN messages; Muslims are generally depicted as dangerous and compared with terrorists and their religion and culture are described as the opposite of Italian/West values. Something approximating to a “moral panic” around this issue has ensued. Integral to this are notions of morality combined with practices of moral entrepreneurship. What follows seeks to highlight the LN’s stereotypical depictions of Islam. This evaluation is important because the LN was a major player in former Prime Minister Silvio Berlusconi’s government (2008-2011) and is still a significant party among the Italian political spectrum. Integral to what follows are the following questions: “Is contemporary Islamic immigration a threat to the Italian (and Padanian) way of life?” and “Are the perceived threats to be found in the periodic uncertainties that societies suffer or might we need to search for wider processes?”
Discovery and validation of graft-versus-host disease biomarkers
Authors: Paczesny Sophie
Published: November 2012

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective tumor immunotherapy available. Although allo-HSCT provides beneficial graft-versus-tumor effects, acute GVHD (aGVHD) is the primary source of morbidity and mortality after HSCT. Diagnosis of aGVHD is typically based on clinical symptoms in one or more of the main target organs (skin, liver, gastrointestinal tract) and confirmed by biopsy. However, currently available diagnostic and staging tools often fail to identify patients at higher risk of GVHD progression, unresponsiveness to therapy, or death. In addition, there are shortcomings in the prediction of GVHD before clinical signs develop, indicating the urgent need for noninvasive and reliable laboratory tests. Through the continuing evolution of proteomics technologies seen in recent years, plasma biomarkers have been identified and validated as promising diagnostic tools for GVHD and prognostic tools for nonrelapse mortality. These biomarkers may facilitate timely and selective therapeutic intervention but should be more widely validated and incorporated into a new grading system for risk stratification of patients and better-customized treatment. This review identifies biomarkers for detecting GVHD, summarizes current information on aGVHD biomarkers, proposes future prospects for the blinded evaluation of these biomarkers, and discusses the need for biomarkers of chronic GVHD.
Combined targeting of AKT and mTOR synergistically inhibits proliferation of hepatocellular carcinoma cells
Authors: Grabinski Nicole , Ewald Florian , Hofmann Bianca T , Staufer Katharina , Schumacher Udo , Nashan Björn , Jücker Manfred
Published: November 2012

Background

Due to the frequent dysregulation of the PI3K/AKT/mTOR signaling pathway, mTOR represents a suitable therapeutic target in hepatocellular carcinoma (HCC). However, emerging data from clinical trials of HCC patients indicate that mTOR inhibition by RAD001 (Everolimus) alone has only moderate antitumor efficacy which may be due to the feedback activation of AKT after mTOR inhibition. In this study, we analyzed the effects of dual inhibition of mTOR and AKT on the proliferation of HCC cell lines. In addition, we measured the feedback activation of each of the AKT isoforms after mTOR inhibition in HCC cell lines and their enzymatic activity in primary samples from HCC patients.

Methods

The activation status of specific AKT isoforms in human HCC samples and corresponding healthy liver tissue was analyzed using an AKT isoform specific in vitro kinase assay. AKT isoform activation after mTOR inhibition was analyzed in three HCC cell lines (Hep3B, HepG2 and Huh7), and the impact of AKT signaling on proliferation after mTOR inhibition was investigated using the novel AKT inhibitor MK-2206 and AKT isoform specific knockdown cells.

Results

AKT isoforms become differentially activated during feedback activation following RAD001 treatment. The combination of mTOR inhibition and AKT isoform knockdown showed only a weak synergistic effect on proliferation of HCC cell lines. However, the combinatorial treatment with RAD001 and the pan AKT inhibitor MK-2206 resulted in a strong synergism, both in vitro and in vivo. Moreover, by analyzing primary HCC tissue samples we were able to demonstrate that a hotspot mutation (H1047R) of PI3KCA, the gene encoding the catalytic subunit of PI3K, was associated with increased in vitro kinase activity of all AKT isoforms in comparison to healthy liver tissue of the patient.

Conclusion

Our results demonstrate that dual targeting of mTOR and AKT by use of RAD001 and the pan AKT inhibitor MK-2206 does effectively inhibit proliferation of HCC cell lines. These data suggest that combined treatment with RAD001 and MK-2206 may be a promising therapy approach in the treatment of hepatocellular carcinoma.
Involvement of formyl peptide receptors in receptor for advanced glycation end products (RAGE) - and amyloid beta 1-42-induced signal transduction in glial cells
Authors: Slowik Alexander , Merres Julika , Elfgen Anne , Jansen Sandra , Mohr Fabian , Wruck Christoph J , Pufe Thomas , Brandenburg Lars-Ove
Published: November 2012

Background

Recent studies suggest that the chemotactic G-protein-coupled-receptor (GPCR) formyl-peptide-receptor-like-1 (FPRL1) and the receptor-for-advanced-glycation-end-products (RAGE) play an important role in the inflammatory response involved in neurodegenerative disorders such as Alzheimer’s disease (AD).

Therefore, the expression and co-localisation of mouse formyl peptide receptor (mFPR) 1 and 2 as well as RAGE in an APP/PS1 transgenic mouse model using immunofluorescence and real-time RT-PCR were analysed. The involvement of rat or human FPR1/FPRL1 (corresponds to mFPR1/2) and RAGE in amyloid-β 1–42 (Aβ1-42)-induced signalling were investigated by extracellular signal regulated kinase 1/2 (ERK1/2) phosphorylation. Furthermore, the cAMP level in primary rat glial cells (microglia and astrocytes) and transfected HEK 293 cells was measured. Formyl peptide receptors and RAGE were inhibited by a small synthetic antagonist WRW4 and an inactive receptor variant delta-RAGE, lacking the intracytoplasmatic domains.

Results

We demonstrated a strong increase of mFPR1/2 and RAGE expression in the cortex and hippocampus of APP/PS1 transgenic mice co-localised to the glial cells. In addition, the Aβ1-42-induced signal transduction is dependant on FPRL1, but also on FPR1. For the first time, we have shown a functional interaction between FPRL1/FPR1 and RAGE in RAGE ligands S100B- or AGE-mediated signalling by ERK1/2 phosphorylation and cAMP level measurement. In addition a possible physical interaction between FPRL1 as well as FPR1 and RAGE was shown with co-immunoprecipitation and fluorescence microscopy.

Conclusions

The results suggest that both formyl peptide receptors play an essential role in Aβ1-42-induced signal transduction in glial cells. The interaction with RAGE could explain the broad ligand spectrum of formyl peptide receptors and their important role for inflammation and the host defence against infections.
Cabozantinib in Patients With Advanced Prostate Cancer: Results of a Phase II Randomized Discontinuation Trial
Authors: Smith David C. , Smith Matthew R. , Sweeney Christopher , Elfiky Aymen A. , Logothetis Christopher , Corn Paul G. , Vogelzang Nicholas J. , Small Eric J. , Harzstark Andrea L. , Gordon Michael S. , Vaishampayan Ulka N. , Haas Naomi B. , Spira Alexander I. , Lara Primo N. , Lin Chia-Chi , Srinivas Sandy , Sella Avishay , Schöffski Patrick , Scheffold Christian , Weitzman Aaron L. , Hussain Maha
Published: November 2012

Purpose

Cabozantinib (XL184) is an orally bioavailable tyrosine kinase inhibitor with activity against MET and vascular endothelial growth factor receptor 2. We evaluated the activity of cabozantinib in patients with castration-resistant prostate cancer (CRPC) in a phase II randomized discontinuation trial with an expansion cohort.

Patients and Methods

Patients received 100 mg of cabozantinib daily. Those with stable disease per RECIST at 12 weeks were randomly assigned to cabozantinib or placebo. Primary end points were objective response rate at 12 weeks and progression-free survival (PFS) after random assignment.

Results

One hundred seventy-one men with CRPC were enrolled. Random assignment was halted early based on the observed activity of cabozantinib. Seventy-two percent of patients had regression in soft tissue lesions, whereas 68% of evaluable patients had improvement on bone scan, including complete resolution in 12%. The objective response rate at 12 weeks was 5%, with stable disease in 75% of patients. Thirty-one patients with stable disease at week 12 were randomly assigned. Median PFS was 23.9 weeks (95% CI, 10.7 to 62.4 weeks) with cabozantinib and 5.9 weeks (95% CI, 5.4 to 6.6 weeks) with placebo (hazard ratio, 0.12; P < .001). Serum total alkaline phosphatase and plasma cross-linked C-terminal telopeptide of type I collagen were reduced by ≥ 50% in 57% of evaluable patients. On retrospective review, bone pain improved in 67% of evaluable patients, with a decrease in narcotic use in 56%. The most common grade 3 adverse events were fatigue (16%), hypertension (12%), and hand-foot syndrome (8%).

Conclusion

Cabozantinib has clinical activity in men with CRPC, including reduction of soft tissue lesions, improvement in PFS, resolution of bone scans, and reductions in bone turnover markers, pain, and narcotic use.
Use of Radiation Therapy in the Last 30 Days of Life Among a Large Population-Based Cohort of Elderly Patients in the United States
Authors: Guadagnolo B. Ashleigh , Liao Kai-Ping , Elting Linda , Giordano Sharon , Buchholz Thomas A. , Shih Ya-Chen Tina
Published: November 2012

Purpose:

Our goal was to evaluate use and associated costs of radiation therapy (RT) in the last month of life among those dying of cancer.

Methods:

We used the Surveillance, Epidemiology, and End Results (SEER) -Medicare linked databases to analyze claims data for 202,299 patients dying as a result of lung, breast, prostate, colorectal, and pancreas cancers from 2000 to 2007. Logistic regression modeling was used to conduct adjusted analyses of potential impacts of demographic, health services, and treatment-related variables on receipt of RT and treatment with greater than 10 days of RT. Costs were calculated in 2009 dollars.

Results:

Among the 15,287 patients (7.6%) who received RT in the last month of life, its use was associated with nonclinical factors such as race, gender, income, and hospice care. Of these patients, 2,721 (17.8%) received more than 10 days of treatment. Nonclinical factors that were associated with greater likelihood of receiving more than 10 days of RT in the last 30 days of life included: non-Hispanic white race, no receipt of hospice care, and treatment in a freestanding, versus a hospital-associated facility. Hospice care was associated with 32% decrease in total costs of care in the last month of life among those receiving RT.

Conclusion:

Although utilization of RT overall was low, almost one in five of patients who received RT in their final 30 days of life spent more than 10 of those days receiving treatment. More research is needed into physician decision making regarding use of RT for patients with end-stage cancer.
High-Dose Vincristine Sulfate Liposome Injection for Advanced, Relapsed, and Refractory Adult Philadelphia Chromosome–Negative Acute Lymphoblastic Leukemia
Authors: O'Brien Susan , Schiller Gary , Lister John , Damon Lloyd , Goldberg Stuart , Aulitzky Walter , Ben-Yehuda Dina , Stock Wendy , Coutre Steven , Douer Dan , Heffner Leonard T. , Larson Melissa , Seiter Karen , Smith Scott , Assouline Sarit , Kuriakose Philip , Maness Lori , Nagler Arnon , Rowe Jacob , Schaich Markus , Shpilberg Ofer , Yee Karen , Schmieder Guenter , Silverman Jeffrey A. , Thomas Deborah , Deitcher Steven R. , Kantarjian Hagop
Published: November 2012

Purpose

Relapsed adult acute lymphoblastic leukemia (ALL) is associated with high reinduction mortality, chemotherapy resistance, and rapid progression leading to death. Vincristine sulfate liposome injection (VSLI), sphingomyelin and cholesterol nanoparticle vincristine (VCR), facilitates VCR dose-intensification and densification plus enhances target tissue delivery. We evaluated high-dose VSLI monotherapy in adults with Philadelphia chromosome (Ph) –negative ALL that was multiply relapsed, relapsed and refractory to reinduction, and/or relapsed after hematopoietic cell transplantation (HCT).

Patients and Methods

Sixty-five adults with Ph-negative ALL in second or greater relapse or whose disease had progressed following two or more leukemia therapies were treated in this pivotal phase II, multinational trial. Intravenous VSLI 2.25 mg/m2, without dose capping, was administered once per week until response, progression, toxicity, or pursuit of HCT. The primary end point was achievement of complete response (CR) or CR with incomplete hematologic recovery (CRi).

Results

The CR/CRi rate was 20% and overall response rate was 35%. VSLI monotherapy was effective as third-, fourth-, and fifth-line therapy and in patients refractory to other single- and multiagent reinduction therapies. Median CR/CRi duration was 23 weeks (range, 5 to 66 weeks); 12 patients bridged to a post-VSLI HCT, and five patients were long-term survivors. VSLI was generally well tolerated and associated with a low 30-day mortality rate (12%).

Conclusion

High-dose VSLI monotherapy resulted in meaningful clinical outcomes including durable responses and bridging to HCT in advanced ALL settings. The toxicity profile of VSLI was predictable, manageable, and comparable to standard VCR despite the delivery of large, normally unachievable, individual and cumulative doses of VCR.