bluuebunny/crossref_metadata_2025 huggingface dataset:
Vibration control of the engine body of a vehicle utilizing the magnetorheological roll mount and the piezostack right-hand mount
Authors: Jeon Juncheol , Han Young-Min , Lee Dong-Young , Choi Seung-Bok
Published: July 2013

In this study, a new controllable engine mounting system for vibration control of passenger vehicles is proposed. The proposed mounting system consists of two smart material actuators: a piezostack actuator and a magnetorheological-fluid actuator. First, the dynamic responses of an in-line four-cylinder engine supported by three rubber mounts are mathematically analysed by considering the six-degree-of-freedom motion of the engine body, whose excitation is generated by the inner forces during the engine combustion process. Second, the proper positions of the two actuators are determined. Two magnetorheological mounts are used as roll mounts, and one piezostack mount is used as the right-hand mount, in order to reduce the unwanted engine vibration in a broadband frequency range. Third, the piezostack mount and the magnetorheological mount are designed and manufactured, followed by installation in the engine mounting system. Subsequently, for effective vibration isolation, a sliding-mode controller, which is robust to disturbances and system uncertainties, is designed. Finally, in order to demonstrate the effectiveness of the proposed new engine mounting system, vibration control performances are evaluated by adopting the hardware-in-the-loop simulation test method associated with the sliding-mode controller. The vibration control responses are presented at various engine operating speeds in the time domain and the frequency domain. It was found that the vibration control performance is improved by 30% at an engine speed of 750 r/min and by 17% at an engine speed of 2000 r/min using the proposed engine mounting system associated with the controllers.
Hybrid learning control for improving suppression of hand tremor
Authors: As’arry Azizan , Md Zain Mohd Zarhamdy , Mailah Musa , Hussein Mohamed
Published: July 2013

Patients with hand tremors may find routine activities such as writing and holding objects affected. In response to this problem, an active control technique has been examined in order to lessen the severity of tremors. In this article, an online method of a hybrid proportional–integral control with active force control strategy for tremor attenuation is presented. An intelligent mechanism using iterative learning control is incorporated into the active force control loop to approximate the estimation mass parameter. Experiments were conducted on a dummy hand model placed horizontally in a tremor test rig. When activated by a shaker in the vertical direction, this resembles a postural tremor condition. In the proportional–integral plus active force control, a linear voice coil actuator is used as the main active tremor suppressive element. A sensitivity analysis is presented to investigate the robustness of the proposed controller in a real-time control environment. The findings of this study demonstrate that the intelligent active force control and iterative learning controller show excellent performance in reducing tremor error compared to classic pure proportional, proportional–integral and hybrid proportional–integral plus active force control controllers.
A case of severe thallium poisoning successfully treated with hemoperfusion and continuous veno-venous hemofiltration
Authors: Huang C , Zhang X , Li G , Jiang Y , Wang Q , Tian R
Published: July 2013

Thallium poisoning is a rare condition that is often misdiagnosed, delaying appropriate treatment. Left untreated, thallium toxicity can permanently damage the nervous and digestive systems or, in severe cases, lead to paralysis and death. It is most often treated by an oral administration of Prussian blue. Thallium has a long physiological half-life, and Prussian blue cannot sequester thallium outside the digestive tract. Therefore, the first priority in treating severe thallium poisoning is to lower blood levels as soon as possible. We report the case of a patient with supralethal blood levels of thallium treated successfully using combined hemoperfusion (HP) and continuous veno-venous hemofiltration (CVVH). Three rounds of HP alone decreased blood thallium levels by 20.2%, 34.8%, and 32.2%, while each of the five subsequent rounds of CVVH reduced thallium blood levels by 63.5%, 64.2%, 42.1%, 18.6%, and 22.6%. The reversal of symptoms and prevention of lasting neurological damage indicates that HP, CVVH, 2,3-dimercaptopropane-1-sulfonate, neuroprotective agents along with supportive therapy were used successfully to treat a case of severe thallium poisoning.
Governance and transportation policy networks in the cross-border metropolitan region of Luxembourg: A social network analysis
Authors: Dörry Sabine , Decoville Antoine
Published: July 2013

Two major processes have increased the need for cross-border public transportation policies in European metropolitan regions in the recent past: the imperative of a region’s accessibility within the inter-urban competition and the aspired EU-wide regional harmonization and de-bordering process. Governing such multifaceted issues in cross-border regions requires the implementation of suitable and efficient organizational solutions. In the example of the cross-border metropolitan region of Luxembourg, we discuss the contradicting ‘border effects’ of a complex cross-border governance network. Such flexible policy networks are supposed to make the proclaimed economic, socio-cultural, and spatial European integration work on the very local level. We suggest that the governance typology of Liesbet Hooghe and Gary Marks offers a useful guiding heuristics for function-specific governance arrangements in cross-border regional contexts. We utilize a method mix of a quantitative social network analysis and a complementary qualitative survey to illuminate structural notions of the policy network relations to relate our empirical results to the conceptual debate on governance structures in the politically proclaimed de-bordering regions within the EU.
Being an iPadist
Authors: Randles Clint
Published: July 2013

This column offers the personal reflections of the author on being a member of the band Touch, an iPad performing ensemble composed of music education faculty members and doctoral students at the University of South Florida. The ensemble primarily performed its own arrangements of popular music selections from a number of genres including, but not limited to, rock, hip-hop, and classical. The group began when the iPad was created by Apple in 2010 and had been performing all over the Tampa Bay (Florida) region, Texas, and Georgia, at the time of this publication. In this article, the reflections of the author are presented to inform the profession on how tablet technology can be used in the music performance arena and on how these devices can function as musical instruments in the general music classroom.
Predictors of Symptoms and Site of Death in Pediatric Palliative Patients With Cancer at End of Life
Authors: Schindera Christina , Tomlinson Deborah , Bartels Ute , Gillmeister Biljana , Alli Amanda , Sung Lillian
Published: July 2013

Objective:

To describe how preferences and treatment influence symptoms at end of life and site of death in pediatric cancer.

Methods:

We included 61 pediatric palliative patients with cancer whose parents previously participated in a study that elicited preferences for aggressive chemotherapy versus supportive care alone and who subsequently died. Main outcomes were severe pain and dyspnea proximal to death and site of death.

Results:

Choice of aggressive chemotherapy predicted significantly more severe pain (odds ratio [OR] 3.1, 95% confidence interval [CI] 1.0-9.6; P = .049). Intravenous chemotherapy 4 weeks before death predicted severe dyspnea (OR 15.8, 95% CI 3.7-67.5; P < .001) and death outside the home (OR 0.3, 95% CI 0.1-0.9; P = .038).

Conclusions:

Parental choice of aggressive chemotherapy and more aggressive treatment proximal to death predicted more pain, dyspnea, and death in hospital. Strategies to improve quality of life are needed.
Major Incongruence and Career Development Among American and South Korean College Students
Authors: Shin Joo Yeon , Steger Michael F. , Lee Ki-Hak
Published: July 2013

The present study examined whether college students who have academic majors that are incongruent with their career aims experience diminished career development. Because the value placed on self-expression differs across cultures, we tested hypotheses in both the United States ( N = 301) and South Korea ( N = 200). Similar proportions of American (20.2%) and South Korean students (25.5%) reported having an incongruent major. In both samples, students with incongruent majors reported significantly lower levels of career decision self-efficacy, meaningful work, and calling, with medium effect sizes. Potential moderators and mediator in the link of major incongruence to calling and meaningful work were also examined. The patterns of relations among major incongruence and career development indicators (i.e., career decision self-efficacy, meaningful work, and calling) did not differ by nationality or the levels of collectivism, indicating no significant moderating effects. Career decision self-efficacy was found to partially mediate the relation of major incongruence to calling and meaningful work in both samples. These results indicate that major incongruence relates to lower sense of calling and meaningful work in part because of decreased career decision self-efficacy. Directions for future research are discussed.
Exploring the Role of Work Volition Within Social Cognitive Career Theory
Authors: Duffy Ryan D. , Bott Elizabeth M. , Allan Blake A. , Autin Kelsey L.
Published: July 2013

The current study examined the role of work volition within social cognitive career theory (SCCT; Lent, Brown, & Hackett, 1994) with a sample of 292 undergraduate students in science-related majors. Students with higher levels of volition endorsed higher levels of science self-efficacy, outcome expectations, interests, and goals. Analyses revealed that work volition was a significant moderator in the link of self-efficacy and outcomes expectations and self-efficacy and goals; stronger links were found in students with lower levels of volition. A structural model was tested with all hypothesized SCCT paths and examined whether work volition continued to moderate these two paths. The model was an excellent fit to the data, and all theorized direct and indirect effects were significant. However, in the full model, work volition was no longer a significant moderator, suggesting that the direction and strength of the relations within the SCCT model are equivalent for students at varying levels of work volition. Practical implications are discussed.
New Options for Usability Testing Projects in Business Communication Courses
Authors: Jameson Daphne A.
Published: July 2013

The increasing availability of recording technologies makes it easier to include usability testing projects in business communication courses. Usability testing is a method of discovering whether people can navigate, read, and understand a print or electronic communication well enough to achieve a particular purpose in a reasonable time frame. Usability projects increase students’ knowledge and motivation by forcing them to experience the audience’s frustrations with poorly written and designed communications. By following the suggestions and examples provided, faculty can develop effective usability project materials and capitalize on new technologies for data collection and sharing.
Working Memory Contributes to Elevated Motor Activity in Adults With ADHD
Authors: Hudec Kristen L. , Alderson R. Matt , Kasper Lisa J. , Patros Connor H. G.
Published: July 2013

Objective: The relationship between working memory (WM) and objectively measured motor activity was examined in adults with ADHD and healthy controls (HCs). Method: Thirty-five adults (ADHD = 20, HC = 15) were grouped using self-report and collateral-report measures in addition to a semistructured clinical interview. All participants completed control conditions with minimal WM demands, and separate phonological (PH) and visuospatial (VS) WM tasks with recall demands ranging from four to seven stimuli. Results: The ADHD group exhibited significantly more motor activity relative to the HC group, and both groups exhibited greater activity during PH and VS WM tasks, relative to control conditions. Finally, the central executive (CE) and PH storage/rehearsal subsystems were associated with large-magnitude between-group differences in activity. Conclusion: Findings suggest that increased demands on WM, particularly the CE and PH storage/rehearsal, contribute to ADHD-related hyperactivity, though a portion of excessive motor activity in adults with ADHD may occur independently of WM demands.
Police Departments’ Use of Facebook
Authors: Lieberman Joel D. , Koetzle Deborah , Sakiyama Mari
Published: July 2013

Police departments (PDs) are increasingly using social networking sites (SNS) as a method of public communication. Over 75% of the largest U.S. departments currently have a presence on at least one of the three major SNS (i.e., Facebook, Twitter, and MySpace). However, little is known about how departments are actually using these sites. To explore this issue, we conducted a content analysis of messages posted by the 23 largest U.S. PDs using Facebook over a 3-month period. Our results indicate that the content pattern was, to some extent, dependent upon the frequency that departments posted messages. Departments posting more frequently typically used Facebook for crime-related messages, whereas those posting less often were more likely to convey public relations messages. We also identified several message characteristics associated with greater responsiveness on the part of individuals following departments on Facebook. Policy implications of these trends are discussed.
Evaluation of the influences of wax content on the tribological and mechanical performance of polytetrafluoroethylene-blended polyamide
Authors: Ozsoy I , Ozsoy N , Unal H , Mimaroglu A
Published: July 2013

In this study, the influences of wax content on the tribological and mechanical performance of nylon-polytetrafluoroethylene blend were evaluated. Wear tests were carried out using nylon 6 + 10% polytetrafluoroethylene + wax pins on AISI 316 L disc material. The wax percentages in the blend are 2%, 4% and 6% by weight. Tests were carried out at room temperature with applied loads of 50–100 N and sliding speeds of 0.4–1.6 m/s. These conditions are equvilent to a combined pressure and speed factor values of 0.141–5.664 MPa m/s. Although the results showed a slight drop in mechanical properties, the friction coefficients and the wear rates of nylon blend were significantly reduced by the addition of wax filler. The friction coefficient was reduced from 0.29 to 0.13 and the reduction in the wear rate was up to 73%. Furthermore, the results also showed that the change in pressure and speed factor values did not have a significant influence on the specific wear rate values. Finally, micrographs of the the worn surfaces showed the presence of transfer film, deformation and adhesive wear mechanisms.
An importance-performance analysis of food service attributes in gastro-tourism development in Western Tourist Circuit, Kenya
Authors: Obonyo George Otieno , Ayieko Monica Awuor , Kambona Oscar Ouma
Published: July 2013

Tourism development has principally focused on the tangible tourism products thereby overlooking the intangible element such as service. This study aimed to evaluate food service attributes in gastro-tourism development in the Western Tourist Circuit, Kenya. A total of 166 top and middle level managers were selected from 62 hotels for this study using multi-stage sampling method. Several food service attributes were identified and used to structure self-administered questionnaires. The data collected were analyzed using descriptive statistics, Factor, regression and importance-performance analysis. The findings indicate that perceived importance-performance of food service attributes in gastro-tourism development varied considerably. Three factors identified were food service output, food service input both perceived to be important with good performance; and food service process perceived important but hoteliers’ performance on the same was poor. The findings provide intuitively appealing strategies for hoteliers and tourism promoters in Western Tourist Circuit, Kenya to set priorities for developing gastro-tourism through food service attributes.
How images work: An analysis of a visual intervention used to facilitate a difficult conversation and promote understanding
Authors: Chapman Mimi V , Hall William J , Colby Robert , Sisler Laurel AG
Published: July 2013

This study centers on an intervention that uses visual methods to structure conversations among teachers about their undocumented Latino/Latina immigrant students living in the US. Given negative perceptions of undocumented immigrants and cultural misunderstandings, recent demographic shifts have challenged many communities, and presented issues especially relevant to majority-culture teachers who teach immigrant students. We describe an innovative intervention methodology that incorporates photographs with facilitated discussion using Visual Thinking Strategies to promote awareness, empathy, and understanding. This study uses qualitative data to identify the ways in which images function to facilitate difficult discussions; to determine the relationship between images, facilitated discussion, and attitude shifts; and to determine whether such attitude shifts are schema changes. Findings show images effectively engage participants in discussion, elicit openness and reflection, and increase empathy. Indications of schema change derive from participants’ descriptions of shifts in awareness, perspective-taking, attitude change, and more complex thinking about Latino/Latina immigrants.
Cross-cultural transition: International teachers’ experience of ‘culture shock’
Authors: Roskell Donna
Published: July 2013

Decades of ‘culture shock’ research has generally focused on student and business sojourners; few studies have examined the experience of teachers who relocate abroad to teach in international schools. This study addresses this imbalance and examines the perspective of 12 teachers who experienced cross-cultural transition in moving abroad to teach in an international school in South East Asia. An underlying assumption is that such teachers will inevitably experience some degree of culture shock. This study proffers a detailed description and analysis of the first year of these 12 teachers, delineating how they negotiated the stages of culture shock and whether they adjusted successfully. Their experience is also interpreted and discussed from the perspective of ‘loss’.
Friendship in young children: Construction of a behavioural sociometric method
Authors: van Hoogdalem Anne-Greth , Singer Elly , Eek Anneloes , Heesbeen Daniëlle
Published: July 2013

We need methods to measure friendship among very young children to study the beginnings of friendship and the impact of experiences with friendship for later development. This article presents an overview of methods for measuring very young children’s friendships. A behavioural sociometric method was constructed to study degrees of friendship among children in daycare centres. Friendship indications of earlier studies were verified. Data were collected by behavioural observations of 674 dyads during their free play in daycare groups. Explorative factor analysis showed a strong significant relationship among playing together, prosocial behaviour, initiatives and imitation, which could be explained by friendship. This association with friendship was not found for quarrels, rejections and proximity during snack and lunch times. Our study showed that the number of children who have one or more friends in daycare depends on the behavioural criteria used in several studies.
Fibrinogen Level as a Surrogate for the Outcome of Thrombolytic Therapy Using Tissue Plasminogen Activator for Acute Lower Extremity Intravascular Thrombosis
Authors: Skeik Nedaa , Gits Colton C. , Ehrenwald Eduardo , Cragg Andrew H.
Published: July 2013

Purpose:

Monitoring of fibrinogen level is used to predict bleeding during lower extremity tissue plasminogen activator (tPA) infusions for peripheral arterial or venous thrombolysis. This practice is not fully addressed in the literature.

Materials and Methods:

We retrospectively reviewed fibrinogen levels and studied bleeding rate from charts of patients who underwent lower extremity tPA infusions at a single hospital from January 2010 to May 2012.

Results:

The rate of thrombolytic success did not correlate with fibrinogen level ( P = .53). The rate of major bleeding was significantly higher for patients with a fibrinogen level at or below 150 mg/dL ( P = .01). Patients whose tPA infusion was terminated within 46 hours had significantly lower rates of major bleeding ( P = .01) and thrombolytic failure ( P < .01). Periprocedural systolic blood pressure above 160 mm Hg was a risk factor for major bleeding ( P = .02). There was no association between concomitant aspirin use ( P = .90, .51) or hourly tPA dose ( P = .71, .62) and thrombolytic success or major bleeding, respectively.

Conclusion:

Fibrinogen level ≤150 mg/dL is associated with increased risk of major bleeding during tPA infusions. We suggest serial fibrinogen measurement as a viable method to monitor bleeding risk during lower extremity tPA infusions.
Older, Wiser, and a Bit More Badass? Exploring Differences in Juvenile and Adult Gang Members’ Gang-Related Attitudes and Behaviors
Authors: Watkins Adam M. , Moule Richard K.
Published: July 2013

Concerns regarding older gang members have persisted for nearly a century, and yet, these members have received minimal attention from gang scholars. Drawing conceptually from Thornberry, Krohn, Lizotte, Smith, and Tobin’s enhancement model and recent research on gang embeddedness, this study uses data from active gang members ( N = 99) to qualitatively compare juvenile and adult gang members’ gang-related attitudes and behaviors. This research finds considerable overlap in the responses of juvenile and adult gang members. Both groups defined the gang in social terms and expressed a willingness to violently defend gang turf. Adult members, however, reported greater ownership of multiple firearms, supporting Spergel’s contention that lethal violence is more common among adult members due to greater availability of “sophisticated” weapons. The theoretical and policy implications of these findings are discussed.
Examining Leader–Follower Congruence of Social Responsibility Values in Transformational Leadership
Authors: Groves Kevin S.
Published: July 2013

Recent reviews of corporate social responsibility (CSR) research indicate a need for studies of micro-level influence processes addressing CSR values. Transformational leadership is a values-laden influence process whereby leaders elicit superior follower performance through the alignment of work values. Using data from 129 leaders and 582 of their direct reports, this study’s results demonstrated that leader CSR values were associated with transformational leadership. Transformational leadership was positively associated with follower stakeholder CSR values and negatively related to follower shareholder CSR values. Leader stakeholder CSR values moderated the relationship between transformational leadership and follower stakeholder values, offering evidence of leader–follower value congruence while addressing a limitation of prior studies that adopted perceptual measures of values congruence. Implications for transformational leadership theory, practice, and future research are discussed.
Gender Role Self-Concept, Categorical Gender, and Transactional-Transformational Leadership
Authors: Wolfram Hans-Joachim , Gratton Lynda
Published: July 2013

Prior research has shown that female managers are more likely to display transactional–transformational leadership, but they are less likely than their male colleagues to benefit from this in terms of leadership effectiveness. The aim of this study is to address this intriguing finding. Our expectations were that female managers need masculinity so that their leadership can display positive effects on perceived workgroup performance, whereas androgyny would be advantageous in male managers. We collected data from 67 workgroups, and asked managers to report on their gender role self-concept as well as workgroup performance, and 473 workgroup members to report on their manager’s leadership style. Our analyses revealed that, expectedly, androgyny might be advantageous in male managers using contingent reward, intellectual stimulation, and charisma/inspiration. For female managers, however, a lack of gender-typical attributes might be disadvantageous, especially when using charisma/inspiration.
Pure Transvaginal Ventral Hernia Repair in Humans
Authors: Wood Stephanie G. , Panait Lucian , Duffy Andrew J. , Bell Robert L. , Roberts Kurt E.
Published: July 2013

Introduction. Transvaginal natural orifice transluminal endoscopic surgery procedures are at the forefront of minimally invasive innovation, remarkable for shorter recovery times and decreased postoperative pain. We aim to demonstrate a novel technique of pure transvaginal laparoscopic ventral hernia repair in a series of patients performed in our institution. Technique Description. The patient was placed in lithotomy position and steep Trendelenburg. A 2-cm transverse colpotomy incision was made and a SILS port was introduced. One 12-mm trocar and two 5-mm trocars were placed through the SILS port and standard straight laparoscopic instruments were used. An appropriately sized round mesh was deployed within a specimen retrieval bag into the peritoneal cavity. Complete anterior circumferential fixation of the mesh was achieved using an AbsorbaTack device. The colpotomy incision was closed. Results. There were a total of 6 pure transvaginal ventral hernia repair procedures performed in our institution between November 2010 and February 2012. The first case was converted to an open procedure after a rectal injury was recognized and repaired. Two patients had transient urinary retention that resolved after 24 hours. One patient had vaginal wound granulation noted at 2 months postoperatively. No long-term complications or recurrences were noted with a median follow-up of 9 months. The mean operative time was 107 minutes. Conclusion. Our initial experience with transvaginal ventral hernia repair in humans suggests that this procedure is feasible, safe, and associated with improved cosmetic results.
Subxyphoid Thyroidectomy
Authors: Sharata Ahmed , Aliabadi-Wahle Shaghayegh , Bhayani Neil H. , Kurian Ashwin A. , Reavis Kevin M. , Dunst Christy M. , Swanstrom Lee L.
Published: July 2013

Objective. The cultural desire to avoid cervical incisions and increasing concern for cosmetic outcomes has motivated surgeons to develop alternative approaches to thyroid surgery. The Direct Drive Endoscopic System (DDES) platform combines a flexible endoscope with a pair of separately controlled articulating instruments through a single, flexible, access system. We hypothesized that the DDES platform would permit single-incision minimally invasive thyroid lobectomy without robotic assistance. Methods. This is a single-cadaver feasibility study. A single, 2.2-cm subxyphoid incision was used for access. The platform’s 55-cm flexible sheath was secured to the operating table rails and introduced into the subcutaneous space. A flexible pediatric endoscope was simultaneously introduced with 2 interchangeable 4-mm instruments. Blunt dissection and electrocautery were used to create the tunnel in the otherwise free central plane. The thyroid was dissected using a superior to inferior technique while maintaining the critical steps of traditional thyroid surgery. A Veress needle introduced through the lateral neck provided additional retraction. Results. The total operating time was 2.5 hours. The subcutaneous tunnel was safe and accommodated the DDES well. Visualization was adequate. Graspers, scissors, and hook cautery were used to complete the lobectomy. The ergonomics, articulation, and strength of the instrumentation were sufficient. Conclusions. Subxyphoid thyroidectomy is technically possible and avoids the difficulties inherent to a transaxillary approach while still avoiding cosmetically unappealing cervical scars. Continued technological refinement will only expand the therapeutic possibilities of flexible endoscopy while minimizing the physical insult to patients and maximizing aesthetics for patients.
Investigative Journalism in Central and Eastern Europe
Authors: Stetka Vaclav , Örnebring Henrik
Published: July 2013

This article presents a comparative study of investigative journalism in nine countries in the Central and Eastern European region (Bulgaria, the Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, and Slovakia). The purpose is descriptive and analytical. Descriptively, the article charts the presence and provision of investigative journalism across the region and inventories and assesses the various funding forms that exist against the background of the recent (2008–2009) financial crisis. Analytically, the article focuses on assessing the relative autonomy (defined as autonomy from external actors) and effects (defined as the removal from office and sentencing of political actors revealed to be engaged in legal and moral transgressions, commonly various forms of corruption). The article finds investigative journalism across the region in general to be weak in terms of autonomy and effects, but stronger in countries that have had more stable and richer media markets (notably Estonia, Poland, and the Czech Republic). The article further finds that in some countries (notably Romania and Bulgaria), alternative news online sources play an increasingly important role as providers of investigative journalism.
Preparing for safety issues following drug approval: pre-approval risk management considerations
Authors: Dieck Gretchen S. , Sharrar Robert G.
Published: July 2013

Risk management plans and risk minimization plans as well as postapproval commitment studies are based on risks identified pre-approval that need to be further characterized or minimized in the postmarketing environment. Although the implementation of these activities are conducted in the postapproval arena, the design of the plans and studies as well as the development of effective postapproval tools and mitigation strategies should be carried out pre-approval. The pre-approval period also provides the opportunity to fully understand the treatment population that is included in the clinical trial program and to determine how the target population for the drug after approval may differ from the clinical trial patient population. When regulators or sponsors have expressed concerns about safety issues identified during clinical development, the result may be a postapproval commitment in the form of a registry or an observational safety study or, in the US, a Risk Evaluation and Mitigation Strategy (REMS) as a condition of approval. Specific examples are given for risk mitigation activities that can be conducted pre-approval.
Perinatal outcomes following maternal asthma and cigarette smoking during pregnancy
Authors: Hodyl Nicolette A. , Stark Michael J. , Scheil Wendy , Grzeskowiak Luke E. , Clifton Vicki L.
Published: July 2013

Does cigarette smoking in pregnancy explain the increased risk of adverse perinatal outcomes that occur with maternal asthma or does it compound the effect?

Using population based birth records, a retrospective analysis was conducted of all singleton pregnancies in South Australia over 10 years (1999–2008; n=172 305), examining maternal asthma, cigarette smoking and quantity of smoking to estimate odds ratios.

Compared with nonasthmatic females who did not smoke during pregnancy, both asthmatic females who smoked and those who did not smoke during pregnancy had a significantly increased risk of gestational diabetes, antepartum haemorrhage, polyhydramnios, premature rupture of membranes, emergency Caesarean section, and the child being small for gestational age and having congenital abnormalities. These associations suggest that asthma, independently of maternal smoking, increases the risk of these adverse perinatal outcomes. Maternal smoking was itself associated with an increased risk of a number of poor neonatal outcomes, with a dose–response relationship observed. Notably, maternal asthma combined with cigarette smoking significantly increased the risk of preterm birth and urinary tract infections to a greater degree than with either exposure alone.

Maternal asthma and cigarette smoking during pregnancy are both independently associated with adverse perinatal outcomes and, combined, compound the risk of preterm birth and urinary tract infections.
APOMand high-density lipoprotein cholesterol are associated with lung function and per cent emphysema
Authors: Burkart Kristin M. , Manichaikul Ani , Wilk Jemma B. , Ahmed Firas S. , Burke Gregory L. , Enright Paul , Hansel Nadia N. , Haynes Demondes , Heckbert Susan R. , Hoffman Eric A. , Kaufman Joel D. , Kurai Jun , Loehr Laura , London Stephanie J. , Meng Yang , O’Connor George T. , Oelsner Elizabeth , Petrini Marcy , Pottinger Tess D. , Powell Charles A. , Redline Susan , Rotter Jerome I. , Smith Lewis J. , Soler Artigas María , Tobin Martin D. , Tsai Michael Y. , Watson Karol , White Wendy , Young Taylor R. , Rich Stephen S. , Barr R. Graham
Published: July 2013

Chronic obstructive pulmonary disease (COPD) is linked to cardiovascular disease; however, there are few studies on the associations of cardiovascular genes with COPD.

We assessed the association of lung function with 2100 genes selected for cardiovascular diseases among 20 077 European-Americans and 6900 African-Americans. We performed replication of significant loci in the other racial group and an independent consortium of Europeans, tested the associations of significant loci with per cent emphysema and examined gene expression in an independent sample. We then tested the association of a related lipid biomarker with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio and per cent emphysema.

We identified one new polymorphism for FEV1/FVC (rs805301) in European-Americans (p=1.3×10−6) and a second (rs707974) in the combined European-American and African-American analysis (p=1.38×10−7). Both single-nucleotide polymorphisms (SNPs) flank the gene for apolipoprotein M (APOM), a component of high-density lipoprotein (HDL) cholesterol. Both were replicated in an independent cohort. SNPs in a second gene related to apolipoprotein M and HDL,PCSK9, were associated with FEV1/FVC ratio among African-Americans. rs707974 was associated with per cent emphysema among European-Americans and African-Americans andAPOMexpression was related to FEV1/FVC ratio and per cent emphysema. Higher HDL levels were associated with lower FEV1/FVC ratio and greater per cent emphysema.

These findings suggest a novel role for the apolipoprotein M/HDL pathway in the pathogenesis of COPD and emphysema.
Alveolar macrophage proteinase/antiproteinase expression in lung function and emphysema
Authors: Ishii Takeo , Abboud Raja T. , Wallace Alison M. , English John C. , Coxson Harvey O. , Finley Richard J. , Shumansky Karey , Paré Peter D. , Sandford Andrew J.
Published: July 2013

Alveolar macrophages play an important role in chronic obstructive pulmonary diseaseviaproduction of matrix metalloproteinases (MMPs) and cathepsins as well as their inhibitors, tissue inhibitors of metalloproteinases and cystatin C. We hypothesised that expression levels of these molecules by alveolar macrophages at baseline and after stimulation would be influenced by genotype and associated with chronic obstructive pulmonary disease phenotypes.

Quantitative PCR and ELISAs/gelatine zymography were used to investigate expression levels of mRNA and protein, respectively. The relationships of expression with genotype, pulmonary function and emphysema were analysed.

The results showed that basal expression level ofMMP12mRNA was inversely related to the diffusing capacity of the lung for carbon monoxide/alveolar volume and to forced expiratory volume in 1 s/forced vital capacity after correction for multiple comparisons. The expression level of MMP12 protein stimulated with lipopolysaccharide was also inversely related to the diffusing capacity of the lung for carbon monoxide/alveolar volume and was positively related to the extent of emphysema. The basal expression ofMMP1mRNA was positively correlated with the extent of emphysema. Cathepsin L protein level was positively associated with forced expiratory volume in 1 s % predicted.

We conclude that increased MMP12 and MMP1 expression may play a role in the pathogenesis of emphysema. Cathepsin L and MMP9 may be involved in the development of airflow limitation.
Propofol sedation for flexible bronchoscopy: a randomised, noninferiority trial
Authors: Grendelmeier Peter , Tamm Michael , Pflimlin Eric , Stolz Daiana
Published: July 2013

Propofol has been established as a reliable method for sedation in flexible bronchoscopy. There are no data comparing propofol administered as intravenous bolusesversuscontinuous infusion.

702 consecutive patients undergoing flexible bronchoscopy were randomly allocated to receive intravenous propofol using either an intermittent bolus technique or a continuous infusion. The primary end-point was the number of adverse events assessed at the end of flexible bronchoscopy and at 24 h.

The number of any adverse event was similar in both randomised groups (219versus211, p=0.810). There were complications in eight cases (seven major bleedings, one respiratory failure). As compared with the bolus group, the amount of propofol required was significantly higher in the infusion group (226 ±147 mgversus308±204.8 mg, p<0.0001). In a multivariate regression model, this difference remained significant independent of the duration and the interventions performed during the procedure. The duration of bronchoscopy was significantly longer in the infusion group (median 14 (interquartile range 9–24)versus17 (12–27) min, p<0.0001).

Propofol continuous infusion is as safe as bolus administration; however, it is associated with higher propofol requirements and a longer duration of the bronchoscopy.
Wave propagation of cortical population activity under urethane anesthesia is state dependent
Authors: Wanger Tim , Takagaki Kentaroh , Lippert Michael T , Goldschmidt Jürgen , Ohl Frank W
Published: July 2013

Background

Propagating waves of excitation have been observed extensively in the neocortex, during both spontaneous and sensory-evoked activity, and they play a critical role in spatially organizing information processing. However, the state-dependence of these spatiotemporal propagation patterns is largely unexplored. In this report, we use voltage-sensitive dye imaging in the rat visual cortex to study the propagation of spontaneous population activity in two discrete cortical states induced by urethane anesthesia.

Results

While laminar current source density patterns of spontaneous population events in these two states indicate a considerable degree of similarity in laminar networks, lateral propagation in the more active desynchronized state is approximately 20% faster than in the slower synchronized state. Furthermore, trajectories of wave propagation exhibit a strong anisotropy, but the preferred direction is different depending on cortical state.

Conclusions

Our results show that horizontal wave propagation of spontaneous neural activity is largely dependent on the global activity states of local cortical circuits.
Acute stress show great influences on liver function and the expression of hepatic genes associated with lipid metabolism in rats
Authors: Gao Xiaoling , Zeng Yuaner , Liu Shuqiang , Wang Shuling
Published: July 2013

Background

The theory of Chinese medicine believes rage harms normal liver function, namely ’raged impairing liver' in short. The purpose of this study is to investigate the impact of acute stress on liver lipid metabolism in rats.

Methods and results

Comparison of liver function indicators, serum lipid level of rats under acute stress and normal rats, as well as detection of liver tissue in the SR - BI, ABCG5 and ABCG8 protein and gene expression changes. Acute stressed rats had shown a lower serum levels of albumin (P<0.01), HDL- cholesterol (P<0.01) than normal rats, with higher serum levels of globulin (P<0.01) and LDL-cholesterol (P<0.05). Acute stressed rat’s liver tissue exhibited a lower protein expression of ABCG5 (P<0.05), ABCG8 (P<0.01) and a higher level of SR-BI (P<0.05), compared with to normal rats. Furthermore, liver gene expression of ABCG5 (P<0.01) and ABCG8 (P<0.05) were lower in acute stressed rats than in normal rats, while SR-BI was higher in acute stressed rats than in normal rats (P<0.01).

Conclusions

Acute stress had a direct influence on rat’s liver lipid metabolism.
Neuropilin2 regulates the guidance of post-crossing spinal commissural axons in a subtype-specific manner
Authors: Tran Tracy S , Carlin Edward , Lin Ruihe , Martinez Edward , Johnson Jane E , Kaprielian Zaven
Published: July 2013

Background

Spinal commissural axons represent a model system for deciphering the molecular logic that regulates the guidance of midline-crossing axons in the developing central nervous system (CNS). Whether the same or specific sets of guidance signals control the navigation of molecularly distinct subtypes of these axons remains an open and largely unexplored question. Although it is well established that post-crossing commissural axons alter their responsiveness to midline-associated guidance cues, our understanding of the repulsive mechanisms that drive the post-crossing segments of these axons away from the midline and whether the underlying guidance systems operate in a commissural axon subtype-specific manner, remains fragmentary at best.

Results

Here, we utilize axonally targeted transgenic reporter mice to visualize genetically distinct dorsal interneuron (dI)1 and dI4 commissural axons and show that the repulsive class 3 semaphorin (Sema3) guidance receptor Neuropilin 2 (Npn2), is selectively expressed on the dI1 population and is required for the guidance of post-crossing dI1, but not dI4, axons. Consistent with these observations, the midline-associated Npn2 ligands, Sema3F and Sema3B, promote the collapse of dI1, but not dI4, axon-associated growth cones in vitro. We also identify, for the first time, a discrete GABAergic population of ventral commissural neurons/axons in the embryonic mouse spinal cord that expresses Npn2, and show that Npn2 is required for the proper guidance of their post-crossing axons.

Conclusions

Together, our findings indicate that Npn2 is selectively expressed in distinct populations of commissural neurons in both the dorsal and ventral spinal cord, and suggest that Sema3-Npn2 signaling regulates the guidance of post-crossing commissural axons in a population-specific manner.
Pricing Payment Cards
Authors: Bedre-Defolie Özlem , Calvano Emilio
Published: July 2013

Payment card networks, such as Visa, require merchants' banks to pay substantial “interchange” fees to cardholders' banks on a per transaction basis. This paper shows that a network's profit-maximizing fee induces an inefficient price structure, oversubsidizing card usage and overtaxing merchants. We show that this distortion is systematic and arises from the fact that consumers make two distinct decisions (membership and usage), whereas merchants make only one (membership). In general, we contribute to the theory of two-sided markets by introducing a model that distinguishes between extensive and intensive margins, thereby explaining why two-part tariffs are useful pricing tools for platforms. (JEL D42, D85, G21, L12)
Laminin Production and Basement Membrane Deposition by Mesenchymal Stem Cells upon Adipogenic Differentiation
Authors: Noro Ariel , Sillat Tarvo , Virtanen Ismo , Ingerpuu Sulev , Bäck Nils , Konttinen Yrjö T. , Korhonen Matti
Published: July 2013

The aim was to study laminin (LM) synthesis, integration, and deposition into the basement membrane (BM) during adipogenesis. Human bone marrow-derived mesenchymal stromal cells (MSCs) were induced along the adipogenic lineage. LM chain mRNA and protein levels were followed using quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence (IF) staining, transmission electron microscopy (TEM), and immunoprecipitation. MSCs produced low levels of LM mRNAs but were not surrounded by BM in IF and TEM imaging. LM-α4, LM-β1, and LM-γ1 mRNAs increased during adipogenesis 3.9-, 5.8-, and 2.8-fold by day 28. LM-411 was immunoprecipitated from the ECM of the differentiated cells. Immunostaining suggested deposition of LM-411 and some LM-421. BM build-up was probably organized in part by integrin (Int) α6β1. At day 28, TEM images revealed BM-like structures around fat droplet-containing cells. The first signs of BM formation and Int α6β1 were seen using IF imaging at day 14. Laminin-411 and Int α6β1 were expressed in vivo in mature human subcutaneous fat tissue. Undifferentiated human MSCs did not organize LM subunits into BM, whereas LM-411 and some LM-421 are precipitated in the BM around adipocytes. This is the first demonstration of LM-411 precipitation during hMSC adipogenesis around adipocytes as a structural scaffold and Int-regulated signaling element.
Utility of a column-switching LC/MS/MS method in cytochrome P450 inhibition assays using human liver microsomes
Authors: Behera Dayanidhi , Pattem Rambabu , Kumar M. Siva Selva , Gudi Girish S.
Published: July 2013

Background: Liquid chromatography-tandem mass spectrometry (LC/MS/MS)-based in vitro cytochrome P450 (CYP) inhibition assays in pooled human liver microsomes using therapeutically relevant probe drugs are recommended by the US Food and Drug Administration to assess the potential for drug-drug interactions. As these assays are used routinely in pharmaceutical drug discovery screening of new chemical entities for drug interaction liabilities, there is a need to have higher analytical throughput. Column-switching methods may offer increased chromatographic throughput while maintaining the quality of data generated.

Methods: In this study, the CYP3A4 inhibition assay was used as a potential application to demonstrate the performance of a dual-column parallel chromatographic system in a column-switching mode. Testosterone 6β-hydroxylation was monitored and IC50 values of known CYP3A4 inhibitors were determined using conventional as well as column-switching LC/MS/MS methods.

Results: Mean IC50 values of ketoconazole, itraconazole and verapamil were 0.056, 0.061 and 23 μM (conventional method) compared to 0.05, 0.057 and 26 μM (column-switching method), respectively. The two different chromatographic methods resulted in IC50 values that were not statistically different and were within a twofold range, demonstrating reproducibility of results. Further, the column-switching method saved nearly 50% of analytical time in comparison to the conventional chromatographic method, indicating increased throughput leading to better utilization of mass spectrometer time without compromising the quality of data.

Conclusions: Similar column-switching methods may be used for other isoforms as well and offer a convenient increased analytical throughput in CYP inhibition assays.
An Interview with Robert K. Ross, M.D.
Authors: Ferris James M.
Published: July 2013

Robert Ross, the President and CEO of The California Endowment, reflects on foundations choices for public policy and systems change, the involvement of The California Endowment in efforts to expand health care access through the Affordable Care Act, and the foundation’s 10-year initiative: Building Healthy Communities.