bluuebunny/crossref_metadata_2025 huggingface dataset:
Re-culturing a university department: a case study
Authors: Giles David , Yates Russell
Published: July 2011

At a time when any number of academics might be forgiven for being distracted by performance-based accountability regimes, some stories and experiences can be found of strong relational and collaborative cultures existing within educational institutions. Indeed, the relational ethos and team priority developed within a particular university department has not only stood the test of time, but is seen as helpful in enabling the individual and collective responsibilities of academic staff. This paper explores leadership re-culturing practices that seek to further enable this continuing relational endeavour. Using a case study approach, the perceptions and experiences of faculty members were drawn on specific re-culturing practices and their influence on the formation of a relational culture within the department. These practices often involve a degree of improvisation and are formed as both proactive and reactive responses to the present ideological context and challenges. What appears to be sustained aspirationally is the leadership’s intent to establish a relational organisational culture which underpins the department’s educational endeavour. This paper seeks to identify a range of leadership practices that influences and re-cultures academics’ individual and collective endeavour within a university department. Such leadership practices focus on open collegial dialogue towards the priority and practice of collaborative relational endeavour in higher education.
Integrative Review of Research Related to Margaret Newman’s Theory of Health as Expanding Consciousness
Authors: Smith Marlaine C.
Published: July 2011

Since 1978 when Margaret Newman first introduced her theory of health as expanding consciousness, the theory has been widely expanded upon by Newman and nursing scholars around the world. This manuscript provides an integrative review of research related to the theory of health as expanding consciousness and analyzes strengths, limitations, and directions for the future. A consistent method of praxis within a unitary, participatory worldview was found. Health as expanding consciousness praxis provides a lens for guiding and interpreting meaning and has cross-cultural appeal and utility.
Patterns of Inquiry
Authors: Lindsay Gail M.
Published: July 2011

Readers are invited to be actors in a text-based theatre, drawn into the stories with their own experiences and discerning patterns that reveal a narrative unity. I show how curriculum-building is inclusive of a teacher’s autobiography, as well as the theoretical/philosophical commitments significant for teaching-learning. This is accomplished through thinking narratively about an experience with my Dad in the healthcare system while simultaneously teaching theory-guided nursing in higher education. Health as expanding consciousness is revealed through a research-as-praxis process that is the content for inquiry.
Compressive mechanical properties of bovine cortical bone under varied loading rates
Authors: Yu B , Zhao G-F , Lim J I , Lee Y-K
Published: July 2011

Bone tissue functions in varied mechanical systems of the body under static and dynamic conditions. Therefore, it is essential to understand the mechanical responses of bone at varied loading rates, especially those at fast loading rates. This study has investigated the effect of loading rate on the compressive mechanical properties of bovine cortical bone. Bone specimens of 3.85 mm in diameter and 7.7 mm in length were compressed longitudinally with the loading rates of 2 to 2000 mm/s (corresponding strain rates of 0.26 to 260 s−1). As a result, bovine cortical bone showed high linear elasticity when the loading rate was slow, and exhibited three definite regions of linear elasticity, plastic deformation, and densification at faster loading rates. The elastic modulus showed no dependency on the loading rate. Compressive strength, strain at fracture, and toughness increased as the loading rate increased under the condition that the loading rates were slower than each critical loading rate of 1000, 100, and 1500 mm/s, respectively. However, all showed no significant changes when the loading rates were faster than the corresponding critical loading rates. In conclusion, as the loading rate increased, changes in the compressive mechanical parameters were different depending on the parameter and the loading rate range. Compressive mechanical behaviour of bovine cortical bone showed a brittle nature under high strain rates (strain rates > 13 s−1). These findings should be reflected in the biomimetic simulation of biomaterials for bone tissue repair and engineering.
Depression and Empathic Accuracy in Couples
Authors: Gadassi Reuma , Mor Nilly , Rafaeli Eshkol
Published: July 2011

We examine the link between depression and empathic accuracy, the ability to infer other people’s thoughts and feelings, as a possible mechanism underlying gender differences in the association between depression and interpersonal difficulties within intimate relationships. Fifty-one heterosexual couples completed questionnaires assessing depressive symptoms and participated in both a lab and a daily diary procedure assessing empathic accuracy. In the lab measures, women’s (but not men’s) higher levels of depressive symptoms were associated with lower empathic accuracy regarding partners’ thoughts and feelings. In the daily diary data, women’s depressive symptoms were specifically associated with lower levels of empathic accuracy for negative feelings but not for positive feelings, and with lower levels of their partners’ empathic accuracy for the women’s negative feelings. Men’s depressive symptoms were again unrelated to levels of empathic accuracy. Our findings suggest that depressive symptoms may have a stronger impact on interpersonal perception in intimate relationships among women than among men.
A Qualitative Study of Family Involvement in Decisions About Life Support in the Intensive Care Unit
Authors: Kryworuchko Jennifer , Stacey Dawn , Peterson Wendy E. , Heyland Daren K. , Graham Ian D.
Published: July 2011

We explored family involvement in decisions about life support interventions in the intensive care unit study using a critical incident technique to focus on specific case exemplars contributed by participants. A total of 6 family members and 9 health care professionals were interviewed. Participants described 2 options (life support or comfort care) and values associated with options: maintaining quality of life, surviving critical illness, minimizing pain and suffering, not being attached to machines, needing adjustment time, and judicious health care resource use. Barriers to involvement included not being offered alternative options; no specific trigger to initiate decision making; dominant influence of professionals’ values; and families lacking understandable information. Family members are unlikely to engage in decision making unless professionals identify the decision and address other barriers to family involvement.
An Experiential Approach to Cultural Intelligence Education
Authors: MacNab Brent R.
Published: July 2011

Cultural intelligence (CQ) represents a promising advancement in the area of cross-cultural training and management. Experiential approaches for CQ development have been proposed as highly effective; however, there is a lack of CQ-specific approaches in the management literature. This work overviews the concept of cultural intelligence and its relevance to management then highlights an experiential CQ education process and framework. The process, designed to increase CQ capacity by engaging in a new cultural contact experience, was initially developed with two cohorts that included a total of 743 management education participants. Details of the process, supporting theory, related teaching materials, participant evaluation, and participant CQ development indicators are presented and future research directions are discussed.
Linking in With LinkedIn®
Authors: Gerard Joseph G.
Published: July 2011

Getting students to network with one another can be one of the biggest challenges in college courses, despite being a highly important function of higher education. Networking can, in fact, lead to that first job or to professional advancement, and technology can improve the success of individual and institutional efforts. This article describes how one instructor moved from a systemwide “Meet the Classmates” assignment nested within the learning management system to the use of a free social networking system, LinkedIn®, and how one icebreaker assignment evolved to three larger, more comprehensive assignments that better leveraged certain social networking system characteristics for greater career preparedness. Exploratory data from 154 respondents from undergraduate capstone strategy courses provides insights into some possible advantages and limitations of the free social networking system to offset networking challenges as well as to enhance those professional and career-based advantages associated with effective network management.
The analysis of inter-laminar stress and electric potential for a laminated piezoelectric plate with interfacial damage
Authors: Yiming Fu , Sheng Li
Published: July 2011

This paper presents a non-linear model for laminated piezoelectric plates with inter-laminar mechanical and electrical damage. The model is based on the general six-degrees-of-freedom plate theory, and the discontinuity of displacement and electric potential on the interfaces are depicted by three shape functions. By using the variation principle, the three-dimensional non-linear equilibrium differential equations of simply supported laminated piezoelectric plates with interfacial damage are derived. Then, an analytical solution is presented by using the finite difference method. In numerical examples, the effects of different damage values, load models, and electric boundary conditions on the inter-laminar stress and electric potential profile of a laminated piezoelectric plate with interfacial imperfections are investigated.
Propagation of plane waves in anisotropic two temperature generalized thermoelasticity
Authors: Singh Baljeet , Bijarnia Rupender
Published: July 2011

The present paper is concerned with the propagation of plane waves in a transversely isotropic generalized thermoelastic solid half-space with two temperatures. The governing equations are modified in the context of Lord and Shulman’s theory of generalized thermoelasticity and are solved to show the existence of three plane waves in the x- z plane. The reflection of these plane waves from a thermally insulated stress-free surface is also studied to obtain a system of three non-homogeneous equations in the reflection coefficients of the reflected waves. For numerical computation of the speeds and reflection coefficients, a particular material is modeled as a transversely isotropic generalized thermoelastic solid half-space. The speeds and reflection coefficients of plane waves are shown graphically against the angle of propagation to observe the effects of anisotropy. The speeds and reflection coefficients of plane waves are also shown graphically against the two-temperature parameter.
Extensional edge waves in pre-stressed incompressible plates
Authors: Pichugin AV , Rogerson GA
Published: July 2011

Consider a semi-infinite layer of an incompressible elastic material subjected to a finite static homogeneous pre-deformation. This paper describes the long-wave low-frequency limiting behaviour of extensional edge waves that may propagate along the free edge of such a layer. The analysis is done by constructing an asymptotic plate theory that describes the extensional motion of thin pre-stressed incompressible plates. The secular equation for edge waves propagating along one of the principal axes of the pre-stress is studied for bi-axial deformations and several specific material models. We show that certain combinations of material models and configurations of pre-stresses do not support the propagation of edge waves, which mirrors the situation with surface waves in pre-stressed media. More unusually, we present a seemingly first explicit example of the non-unique edge wave solutions existing in thin pre-stressed plates.
Improving the performance scalability of the community atmosphere model
Authors: Mirin Arthur A. , Worley Patrick H.
Published: July 2011

The Community Atmosphere Model (CAM), which serves as the atmosphere component of the Community Climate System Model (CCSM), is the most computationally expensive CCSM component in typical configurations. On current and next-generation leadership class computing systems, the performance of CAM is tied to its parallel scalability. Improving performance scalability in CAM has been a challenge, due largely to algorithmic restrictions necessitated by the polar singularities in its latitude–longitude computational grid. Nevertheless, through a combination of exploiting additional parallelism, implementing improved communication protocols, and eliminating scalability bottlenecks, we have been able to more than double the maximum throughput rate of CAM on production platforms. We describe these improvements and present results on the Cray XT5 and IBM BG/P. The approaches taken are not specific to CAM and may inform similar scalability enhancement activities for other codes.
Models and complexity results for performance and energy optimization of concurrent streaming applications
Authors: Benoit Anne , Renaud-Goud Paul , Robert Yves
Published: July 2011

In this paper, we study the problem of finding optimal mappings for several independent but concurrent workflow applications, in order to optimize performance-related criteria together with energy consumption. Each application consists of a linear chain graph with several stages, and processes successive data sets in pipeline mode, from the first to the last stage. The problem is to decide which processors to enroll, at which speed (or mode) to use them, and which stages they should execute. There is a clear trade-off to reach, since running faster and/or more processors leads to better performance, but energy consumption is then very high. Energy savings can be achieved at the price of a lower performance, by reducing processor speeds or enrolling fewer resources. We study the problem complexity on different target execution platforms, ranking from fully homogeneous platforms to fully heterogeneous ones. We consider three mapping strategies: (i) one-to-one mappings, where a processor is assigned a single stage; (ii) interval mappings, where a processor may process an interval of consecutive stages of the same application; and (iii) general mappings, which are fully arbitrary, i.e. a processor may process stages of several distinct applications. Finally, we compare two different models for the computation of the latency, which is the time elapsed between the beginning and the end of the execution of a given data set: with the PATH model, it is computed as the length of the path taken by this data set, while with the WAVEFRONT model, each data set progresses concurrently within a period. For all platform types, all mapping strategies and both latency models, we establish the complexity of several multi-criteria optimization problems, whose objective functions combine period, latency and energy criteria. In particular, we exhibit instances where the problem is NP-hard with concurrent applications, while it can be solved in polynomial time for a single application, and instances whose problem complexity depends upon the latency model.
The Rise of the Productive Non-Place
Authors: Gregory Tim
Published: July 2011

In Non-places: Introduction to an Anthropology of Supermodernity, Marc Augé defines the archetypal spaces of globalization. The defining factor for Augé is that non-places are transitory, hence any effect they have on us is temporary. This article addresses the expansion of non-places into spaces of habitation and the consequences that ensue from perpetual exposure. This article proposes that the middle-class office is a non-place. Giorgio Agamben’s “state of exception” provides a framework for understanding the environment of the contemporary precariat office worker. The non-place and the state of exception share properties of explicit democracy, total visibility, and the perpetual necessity of proving one’s innocence and loyalty. The preservation of a sovereign state is transformed in a non-place office into a series of isolated, individual, and anxious performances in an attempt to preserve one’s employment. The explicit availability of the individual worker prevents the appearance of identity and community.
Evidence-based dialectics
Authors: Morrell Kevin
Published: July 2011

‘Evidence-based policy’ and ‘evidence-based management’ are increasingly popular ways of describing the relationship between research and practice. The majority discussing the evidence-based approach have tended to be in favour: here, ‘believers’. Yet this approach has also attracted critics: ‘heretics’. Understanding of such a division can be enhanced by dialectics: a process which tries to destabilize, reconcile or transcend apparent opposites. This divide is not simply a consequence of differences relating to epistemology, but also aesthetics: a set of reactions to the world seen as art. So, to analyse this divide requires a correspondingly rich model of dialectic. Nietzsche’s Birth of Tragedy offers this in its account of Apolline and Dionysian responses to the world. Dialectics supports a move beyond synchronous critique, and allows speculation as to the future development of the evidence-based approach.
Translating Fanon in the Italian context: Rethinking the ethics of treatment in psychiatry
Authors: Giordano Cristiana
Published: July 2011

Based on two years of ethnographic fieldwork at the Centro Frantz Fanon, an ethnopsychiatric clinic in Northern Italy, this article traces the theoretical and clinical genealogy of Italian ethnopsychiatry as it is conceived and practiced at this clinic. The clinic draws explicitly from the work of Fanon and French ethnopsychologist Tobie Nathan. This genealogy provides a basis for reflection on the ways in which current ethnopsychiatry re-articulates older questions about difference and healing, culture and suffering, and the political dimensions of psychiatry. Although ethnopsychiatry is currently focused on the care of migrants, key issues related to the impact of colonialism on mental illness and the recognition of cultural difference characterized the Italian debate long before the 1980s when increasing numbers of migrants and political refugees started to arrive in Italy.
Estimating the proportion of Danes at high risk of fatal cardiovascular disease
Authors: Sonne Holm Ann-Sofie , Stentebjerg Olsen Gitte , Borglykke Anders , Jørgensen Torben
Published: July 2011

Aims: It has been recommended by several intervention studies to use a high risk approach for cardiovascular disease (CVD) prevention, and the European Guidelines on Cardiovascular Disease Prevention in Clinical Practice (ESC Guidelines) provide a method to identify high risk individuals. Furthermore the ESC Guidelines suggest interventions for the high risk group, with the overall intention to reduce CVD mortality. The ESC Guidelines have not yet been applied in cardiovascular research in Denmark. Therefore, the aim of this study is to estimate the proportion at high risk for fatal CVD in a Danish population. Methods: Data from a population-based cross-sectional study from the Research Centre for Prevention and Health (the former Glostrup Population Studies) from 2006 was used. A total of 2,815 individuals aged 25—64 years were included in the analysis. The criteria listed in ESC Guidelines were used to identify the high risk group. The results were stratified according to age and sex. Results: A total of 21.2% were categorized as high risk for fatal CVD, and 51.6% of the high risk individuals were categorized due to a SCORE risk ≥ 5%. In general more men than women were categorized as high risk within the different age groups. A larger proportion was categorized in high risk in the oldest age groups compared with the younger ones. Conclusions: With the considerably large proportion at high risk —one in five individuals — it is worthwhile considering increasing the attention given to identify high risk individuals. Applying the interventions suggested in the ESC Guidelines to high risk individuals could potentially reduce CVD mortality in Denmark.
Nokia’s MMS: A cultural analysis of mobile picture messaging
Authors: Lillie Jonathan
Published: July 2011

This article takes a cultural studies approach to analyzing what could be termed the ‘cultural uptake’ of a new commercial visual technology, mobile-to-mobile picture messaging, in three key interdependent areas: user adoption, political economic contexts, and textual representation. Nokia’s early investment and marketing of multimedia messaging service (MMS) is juxtaposed to actual trends in user adoption and cultural appropriation, which in turn encouraged the company to deploy narrative practices based on perceived user needs and later focus on popular internet-based services, such as online image sharing. The goal of this study is to highlight the complex contested ground onto which new media technologies ‘emerge,’ while offering a partial, yet multilayered, snapshot of the first few years of a still relatively new, but already pervasive, personal media tool.
Perspectives on theological education in Malawi
Authors: Hisbon Matemba Yonah
Published: July 2011

This article gives an overview of (Christian) Theological Education (CTE) in Malawi. To place the discussion in its appropriate context, information about Malawi is given including the impact of Christianity on the country. The article then describes historical aspects of CTE and highlights some of its inherent shortcomings, before shifting to more recent developments and justifying why Malawi still needs CTE. Next, attention is given to the two main ‘routes’ in CTE provision. Finally, ‘new’ theologies that have emerged in CTE in Malawi are identified and described.
Teaching Religion
Authors: Donnelly Colleen
Published: July 2011

This article argues the importance of including religion in the curriculum of undergraduate studies. Religion is, at its nexus, an ideology, a belief system that reverberates through literature and history. Such knowledge in itself is invaluable for students, introducing them to the difference between ideology and fact and to how ideology becomes intertwined with politics, economics, and other social forces. Introduced to such concepts, students begin to gain a more informed vision of religion which affords them the opportunity to engage in more complex, synthetic interdisciplinary studies in a way that better mirrors our world. They become engaged in critical thinking that takes them beyond their own personal belief systems.
‘Doing the secular’
Authors: Schepelern Johansen Birgitte
Published: July 2011

The academic study of religion at the public university often presents itself as a secular, non-religious, scientific endeavor. The identity of the study is thus firmly rooted within one of the central secular—religious divides, namely that between science and religion. Based on the assumption that such distinctions between religion and the secular (in this case science) are by no means naturally given, but continuously need to be produced and sanctioned in social practice in order to sustain themselves, the article shows how the distinction between religion and science is produced in daily academic practices at two departments for the Study of Religion at Danish universities.
Escaping from Sunday School
Authors: Marten Michael
Published: July 2011

The article argues that, in the teaching of religion at undergraduate level, many students approach understanding the historical or contemporary Middle East in ways that are coloured by what they think is biblical knowledge or basic Christian beliefs. This is less noticeable for students in disciplines such as history or politics. Many history or politics courses that address issues related to the Middle East use Edward Said′s Orientalism to interpret scholarship and attitudes prevalent in the West. I argue that this represents a valid starting point for religion students too, whether dealing with contemporary or historical issues, but the approach often used in other disciplines to teach Said’s work may require rethinking when teaching religion students.
Perspectives on university teaching in the US
Authors: Kurtz Jeffrey B. , Orten Mark R.
Published: July 2011

Higher education in the United States is in crisis. Though powerful, the financial maelstrom that has consumed many institutions may not be the vortex of most significance. We argue that colleges and universities have forsaken their fundamental mission and purposes, and particularly the role of religion in those purposes. We first examine three primary arguments about the relationship between religion and higher education: what may be loosely characterized as explicit separation; the inculcation of ‘academic virtues’; and authentic integration founded upon principles of piety, robust pluralism, and the Reformed tradition. The article concludes by advancing what the last of these relationships might look like, identifying ways teacher—scholars in the arts and humanities might invoke a more authentic integration and collaboratively engage in the necessary conversations about our mission and purposes.
Statistical representativeness of ballast water sampling
Authors: Basurko O C , Mesbahi E
Published: July 2011

The International Maritime Organization’s (IMO’s) G2 guideline (Guidelines for ballast water sampling) clearly states that ballast water samples are required to be representative of the whole ballast water discharged. Enforcement and implementation of the ballast water convention largely depend on defendable case based on evidence that a ship entering territorial waters has not complied with regulations. The statistical representativeness of ballast water samples has been discussed in this study with additional emphasis on practicality of the sampling procedure. The mathematical formula for determining a sample size for a proportion from a finite population has been used to identify the minimum number of samples which could be considered as statistically representative of the ship’s ballast water. Results clearly indicate that a large amount of ballast water, the 16 per cent of ballast water (8000 m3) for a ship discharging 50 000 m3 of ballast water, must be sampled to achieve certain level of confidence which could be translated as a true representation of the ship’s ballast water discharged and potentially used in any further legal actions by states or ship operators.
Introduction of a Guide to Enhance Risk Communication Among Low-Income and Minority Populations
Authors: Rowel Randy , Sheikhattari Payam , Barber Tanyka M. , Evans-Holland Myrtle
Published: July 2011

Low-income populations, especially those belonging to minority groups, are among the most vulnerable groups before, during, and after a natural disaster. One of the factors that can be attributed to their vulnerability is the ineffectiveness of traditional risk communication systems in reaching this population. Many low-income populations are distrustful of government agencies and those who typically communicate risk messages. Consequently, traditional systems are not as effective in reaching these communities. Furthermore, traditional systems have been based on the social media that the general population uses and not based on social networks of disadvantaged populations which are more important than formal channels in these communities for dissemination of information. To bridge the gap, an approach is needed that relies on trusted agencies and leaders to educate and warn low-income communities about possible public health threats. A grassroots approach can enhance the capacity of the risk communication systems to more effectively reach vulnerable populations by engaging grassroots organizations in risk communication activities. The Guide to Enhance Grassroots Risk Communication Among Low-Income Populations provides strategies and guidance that can assist agencies in upgrading their systems for risk communication by building partnerships with local community stakeholders.
Psychometric Evaluation of a Proposed Alzheimer’s Aggression Scale
Authors: Little Kristina G. , Wilks Scott E.
Published: July 2011

The purpose of this study was to evaluate a popular measure of Alzheimer’s disease (AD) memory and behavior problems and to determine whether its aggressive behavior items coalesced empirically as a subscale to form a psychometrically viable AD aggression measure for clinicians. Data from self-report questionnaires were examined from 419 informal AD caregivers in the southern United States. Principal axis factoring revealed a unidimensional solution with robust item loadings on the single factor. Three forms of reliability analysis indicated moderately strong internal consistency on this proposed measure. Evidence of convergent validity analysis was suggested via the measure’s significant correlations to theoretically linked constructs. The proposed measure emerged as a reliable and valid tool for health care practitioners for the appraisal of problematic AD aggression behaviors from the caregiver perspective.
Matching Math Interventions to Students’ Skill Deficits
Authors: Burns Matthew K.
Published: July 2011

The current study demonstrates how conceptual and procedural knowledge can be used as a heuristic to better understand student math difficulties in order to develop interventions and lay the groundwork for future research. Math interventions were implemented with two elementary students using a nonexperimental single-case design. One student demonstrated acceptable conceptual understanding but low procedural knowledge, and the other student demonstrated low conceptual understanding in addition to difficulties with procedural knowledge. The mismatched intervention (e.g., procedural for a student who needs a conceptual intervention) was implemented first for both students, followed by the appropriate intervention. The intervention that was identified as the most appropriate was more effective than the mismatched intervention for both students. The mean percentage of nonoverlapping data was 100% for the matched intervention and 16.5% for the mismatched intervention. Suggestions for future research are included.
Transoral Robotic Surgery for the Treatment of Head and Neck Cancer of Various Localizations
Authors: Aubry Karine , Yachine Mehdi , Lerat Justine , Vivent Muriel , Perez Anne-Frédérique , Scomparin Aurélie
Published: July 2011

Background. Transoral robotic surgery (TORS) is a recent endoscopic technique to resect selected head and neck cancers. Study design. In total, 13 patients underwent TORS procedure for resection of head and neck cancers of various localizations, within the ENT Department of Limoges University Hospital Center between March and October 2010. Results. Tumor localizations were aryepiglottic fold (n = 3), pyriform sinus (n = 2), posterior pharyngeal wall (n = 2), base of tongue (n = 2), lateral pharyngeal wall (n = 2), vallecula (n = 1), and epiglottis (n = 1). Average TORS setup time was 23 minutes. Average TORS operative time was 45 minutes. Average hospital stay was 8.4 days. Conclusions. TORS is a new technique that permits excellent resection of selected head and neck cancers with poor morbidity. Future reports on long-term oncologic and functional outcomes are needed to assess the risks and benefits of this approach compared with external approaches and nonsurgical alternatives.
Statistical aspects of the TNK-S2B trial of tenecteplase versus alteplase in acute ischemic stroke: an efficient, dose-adaptive, seamless phase II/III design
Authors: Levin Bruce , Thompson John LP , Chakraborty Bibhas , Levy Gilberto , MacArthur Robert , Haley E Clarke
Published: July 2011

Background TNK-S2B, an innovative, randomized, seamless phase II/III trial of tenecteplase versus rt-PA for acute ischemic stroke, terminated for slow enrollment before regulatory approval of use of phase II patients in phase III.

Purpose (1) To review the trial design and comprehensive type I error rate simulations and (2) to discuss issues raised during regulatory review, to facilitate future approval of similar designs.

Methods In phase II, an early (24-h) outcome and adaptive sequential procedure selected one of three tenecteplase doses for phase III comparison with rt-PA. Decision rules comparing this dose to rt-PA would cause stopping for futility at phase II end, or continuation to phase III. Phase III incorporated two co-primary hypotheses, allowing for a treatment effect at either end of the trichotomized Rankin scale. Assuming no early termination, four interim analyses and one final analysis of 1908 patients provided an experiment-wise type I error rate of <0.05.

Results Over 1,000 distribution scenarios, each involving 40,000 replications, the maximum type I error in phase III was 0.038. Inflation from the dose selection was more than offset by the one-half continuity correction in the test statistics. Inflation from repeated interim analyses was more than offset by the reduction from the clinical stopping rules for futility at the first interim analysis.

Limitations Design complexity and evolving regulatory requirements lengthened the review process.

Conclusions (1) The design was innovative and efficient. Per protocol, type I error was well controlled for the co-primary phase III hypothesis tests, and experiment-wise. (2a) Time must be allowed for communications with regulatory reviewers from first design stages. (2b) Adequate type I error control must be demonstrated. (2c) Greater clarity is needed on (i) whether this includes demonstration of type I error control if the protocol is violated and (ii) whether simulations of type I error control are acceptable. (2d) Regulatory agency concerns that protocols for futility stopping may not be followed may be allayed by submitting interim analysis results to them as these analyses occur.
Adolescents’ Use of the Emergency Department
Authors: Alderman Elizabeth M. , Avner Jeffrey , Racine Andrew
Published: July 2011

Background: Many of the 18 million emergency department visits by adolescents annually in the United States are for nonurgent problems that might be addressed in a primary care setting. Methods: As part of a larger randomized controlled intervention, 1023 adolescents aged 12 to 21 years registering in an urban pediatric emergency department (PED) were tracked over the subsequent 365 days to record all visits to the PED. Adolescents identifying an adolescent medicine service (AMS) as the primary care source were compared with adolescents receiving primary care elsewhere in an integrated urban medical system (non-AMS) to determine how often after the index PED visit they revisited the PED, returned to primary care (PC), visited a subspecialist (SS), or were hospitalized. Mean values and odds ratios of each type of visit were compared between AMS and non-AMS patients using multivariate logistic and ordinary least squares regressions to control for covariates. Results: AMS patients (n = 124, 12%), compared to non-AMS patients (n = 899, 88%), were more likely female (75% vs 48%, P < .001) and used public insurance (52% vs 40%, P = .017). In unadjusted comparisons, AMS and non-AMS patients did not differ in the probability of any return PED visit (46% vs 37%, P = .052) in the 365 days following the index PED visit but differed in the mean number of return PED visits (1.35 vs 0.93, P = .026). AMS patients were more likely to be hospitalized (15% vs 7%, P = .006) after the index PED visit and also had a greater mean number of hospitalizations (0.41 vs 0.19, P = .048). Multivariate analyses controlling for demographic variables, triage level of initial PED visit, and hospitalizations showed AMS patients returned to primary care after an index PED visit 24.6 days earlier than non-AMS patients ( P = .026). Conclusions: This study demonstrates attending an AMS for primary care predicted earlier return to the primary care provider after an index PED visit. Elements of adolescent specialty care producing such outcomes are worthy of further study.
Predicting survival in malignant mesothelioma
Authors: Musk A.W. , Olsen N. , Alfonso H. , Reid A. , Mina R. , Franklin P. , Sleith J. , Hammond N. , Threlfall T. , Shilkin K.B. , de Klerk N.H.
Published: July 2011

Malignant mesothelioma (MM) of the pleura or peritoneum is a universally fatal disease attracting an increasing range of medical interventions and escalating healthcare costs.

Changes in survival and the factors affecting survival of all patients ever diagnosed with MM in Western Australia over the past five decades and confirmed by the Western Australian Mesothelioma Registry to December 2005 were examined. Sex, age, date and method of diagnosis, site of disease and histological type were recorded. Date of onset of symptoms and performance status were obtained from clinical notes for a sample of cases. Cox regression was used to examine the association of the clinical variables and the 10-yr periods of disease onset with survival after diagnosis.

Survival was inversely related to age, being worse for males (hazard ratio (HR) 1.4, 95% CI 1.2–1.6), and those with peritoneal mesothelioma (HR 1.4, 95% CI 1.1–1.7). Patients with sarcomatoid histology had worse prognosis than patients with epithelioid and biphasic histological subtypes. Survival improved after the 1970s and has made incremental improvements since then. Median (interquartile range) survival by decade, from 1960 until 2005, was 64 (0–198), 177 (48–350), 221 (97–504), 238 (108–502) and 301 (134–611) days; ∼4 weeks of this apparent improvement can be attributed to earlier diagnosis.

With increasing resources and treatment costs for MM over the past 40 yrs, there have been modest improvements in survival but no complete remissions.
Genetic variants associated with severe pneumonia in A/H1N1 influenza infection
Authors: Zúñiga J. , Buendía-Roldán I. , Zhao Y. , Jiménez L. , Torres D. , Romo J. , Ramírez G. , Cruz A. , Vargas-Alarcon G. , Sheu C-C. , Chen F. , Su L. , Tager A.M. , Pardo A. , Selman M. , Christiani D.C.
Published: July 2011

The A/H1N1 influenza strain isolated in Mexico in 2009 caused severe pulmonary illness in a small number of exposed individuals. Our objective was to determine the influence of genetic factors on their susceptibility.

We carried out a case–control association study genotyping 91 patients with confirmed severe pneumonia from A/H1N1 infection and 98 exposed but asymptomatic household contacts, using the HumanCVD BeadChip (Illumina, San Diego, CA, USA).

Four risk single-nucleotide polymorphisms were significantly (p<0.0001) associated with severe pneumonia: rs1801274 (Fc fragment of immunoglobulin G, low-affinity IIA, receptor (FCGR2A) gene, chromosome 1; OR 2.68, 95% CI 1.69–4.25); rs9856661 (gene unknown, chromosome 3; OR 2.62, 95% CI 1.64–4.18); rs8070740 (RPA interacting protein (RPAIN) gene, chromosome 17; OR 2.67, 95% CI 1.63–4.39); and rs3786054 (complement component 1, q subcomponent binding protein (C1QBP) gene, chromosome 17; OR 3.13, 95% CI 1.89–5.17). All SNP associations remained significant after adjustment for sex and comorbidities. The SNPs on chromosome 17 were in linkage disequilibrium.

These findings revealed that gene polymorphisms located in chromosomes 1 and 17 might influence susceptibility to development of severe pneumonia in A/H1N1 infection. Two of these SNPs are mapped within genes (FCGR2A,C1QBP) involved in the handling of immune complexes and complement activation, respectively, suggesting that these genes may confer risk due to increased activation of host immunity.
Trajectories of endurance activity following pulmonary rehabilitation in COPD patients
Authors: Soicher J.E. , Mayo N.E. , Gauvin L. , Hanley J.A. , Bernard S. , Maltais F. , Bourbeau J.
Published: July 2011

Maintenance of physical activity following pulmonary rehabilitation remains a challenge for patients with chronic obstructive pulmonary disease (COPD). The objectives of this study were to identify patterns of endurance activity after completion of pulmonary rehabilitation and to characterise people who succeed and those who have difficulty maintaining endurance activity.

In a longitudinal study embedded within a randomised clinical trial, 206 individuals with COPD underwent a 3-month pulmonary rehabilitation programme. Weekly duration of endurance activity was assessed at 4, 6, 8 and 12 months after the start of rehabilitation. Trajectory modelling was used to determine the most common patterns of activity during the post-rehabilitation phase from 4–12 months.

Three distinct patterns were identified, two of which indicated difficulty in maintaining endurance activity: 61 individuals reported a high activity level at 4 months (2.7 h·week−1) and stayed high; 114 individuals started at a low activity level (mean 1.0 h·week−1) and stayed low; and 31 individuals started high (3.0 h·week−1) and declined. The low activity group was characterised by more severe disease and greater respiratory impairment. The high and declined group had less severe disease and respiratory impairment, but reported greater barriers to exercise.

Pulmonary rehabilitation should include interventions aimed at minimising barriers, in order to induce long-term behaviour change.
Pharmacological treatment of severe, therapy-resistant asthma in children: what can we learn from where?
Authors: Bush A. , Pedersen S. , Hedlin G. , Baraldi E. , Barbato A. , de Benedictis F. , Lødrup Carlsen K.C. , de Jongste J. , Piacentini G.
Published: July 2011

There is a lack of high-quality evidence on what treatment should be used in children with properly characterised severe, therapy-resistant asthma. Data have to be largely extrapolated from trials in children with mild asthma, and adults with severe asthma. Therapeutic options can be divided into medications used in lower doses for children with less severe asthma, and those used in other paediatric diseases but not for asthma (for example, methotrexate). In the first category are high-dose inhaled corticosteroids (ICS) (≤2,000 μg·day−1fluticasone equivalent), oral prednisolone, the anti-immunoglobulin (Ig)E antibody omalizumab, high-dose long-acting β2-agonists, low-dose oral theophylline and intramuscular triamcinolone. If peripheral airway inflammation is thought to be a problem, the use of fine-particle ICS or low-dose oral corticosteroids may be considered. More experimental therapies include oral macrolides, cyclosporin, cytotoxic drugs such as methotrexate and azathioprine, gold salts, intravenous infusions of Ig, subcutaneous β2-agonist treatment and, in those sensitised to fungi, oral antifungal therapy with itraconazole or voriconazole. Those with recurrent severe exacerbations, particularly in the context of good baseline asthma control, are particularly difficult to treat; baseline control and lung function must be optimised with the lowest possible dose of ICS, and allergen triggers and exposures minimised. The use of high-dose ICS, leukotriene receptor antagonists or both at the time of exacerbations can be considered. There is no evidence regarding which therapeutic option to recommend. Better evidence is required for all these treatment options, underscoring the need for the international and co-ordinated approach which we have previously advocated.
Is community-acquired pneumonia an independent risk factor for cardiovascular disease?
Authors: Singanayagam A. , Singanayagam A. , Elder D.H.J. , Chalmers J.D.
Published: July 2011

Community-acquired pneumonia (CAP) is the most frequent infectious cause of death in western countries. The high mortality rate in CAP is commonly related to comorbid conditions such as cardiovascular disease.

Clinical studies in both primary and secondary care settings have identified an increase in short- and long-term risk of cardiovascular events and death from vascular events following acute respiratory infections. The mechanism remains to be fully established, but it has been suggested that the inflammatory state in patients affected by CAP acts to promote platelet activation and thrombosis, and to narrow coronary arteries through vasoconstriction. Acute infections destabilise vascular endothelium and create an imbalance between myocardial oxygen supply and demand, leading to an increased risk of cardiovascular events. Acute infections have been shown to have both systemic effects and local effects on coronary vessels. These effects are mediated through both the host response to infection and, in some cases, direct effects of bacterial infection or bacterial products.

In this review, we discuss the link between CAP and increased risk of cardiovascular events, drawing on existing evidence from clinical and mechanistic studies. Further studies into and increased awareness of this association is warranted to promote novel ways of protecting high-risk patients.
Molecular genetics and clinical features of Chinese idiopathic and heritable pulmonary arterial hypertension patients
Authors: Liu D. , Liu Q-Q. , Eyries M. , Wu W-H. , Yuan P. , Zhang R. , Soubrier F. , Jing Z-C.
Published: July 2011

Mutations of the bone morphogenetic protein type II receptor (BMPR2) gene predispose to pulmonary arterial hypertension (PAH). 290 idiopathic (I)PAH patients and 15 heritable (H)PAH were screened to determine the spectrum and rate ofBMPR2mutations in a large Chinese patient group.

Gene sequencing and multiplex ligation-dependent probe amplification (MLPA®) were used to detect sequence mutations and large rearrangements (RGTs). Total mutation rate was 14.5% (n=42 out of 290) in Chinese IPAH patients, and 53.3% (n=8 out of 15) in HPAH patients. RGT mutation rate was 3.1% (n=7 out of 229) and represented 14% (n=7 out of 50) of all identified mutations. 25BMPR2mutations were newly identified.

Patients in this study were younger than other reported PAH subjects.BMPR2mutation carriers were ∼6 yrs younger at diagnosis than noncarriers (p=0.002), but this relationship was significant only in the female group, which was larger. The proportion of females carrying aBMPR2mutation was half that of males (12.8%versus25.3%; p=0.008).

Our results indicate that the overall genetics of Chinese PAH patients is similar to that of other populations, but the clinical picture differs by the precocity of the disease in the whole patient group, and the lower proportion of females found to carry aBMPR2mutation.
Prevalence of hiatal hernia by blinded multidetector CT in patients with idiopathic pulmonary fibrosis
Authors: Noth I. , Zangan S.M. , Soares R.V. , Forsythe A. , Demchuk C. , Takahashi S.M. , Patel S.B. , Strek M.E. , Krishnan J.A. , Patti M.G. , MacMahon H.
Published: July 2011

Hiatal hernia (HH) is associated with gastro-oesophageal reflux (GOR) and/or GOR disease and may contribute to idiopathic pulmonary fibrosis (IPF). We hypothesised that HH evaluated by computed tomography is more common in IPF than in asthma or chronic obstructive pulmonary disease (COPD), and correlates with abnormal GOR measured by pH probe testing.

Rates of HH were compared in three cohorts, IPF (n=100), COPD (n=60) and asthma (n=24), and evaluated for inter-observer agreement. In IPF, symptoms and anti-reflux medications were correlated with diffusing capacity of the lung for carbon monoxide (DL,CO) and composite physiologic index (CPI). HH was correlated with pH probe testing in IPF patients (n=14).

HH was higher in IPF (39%) than either COPD (13.3%, p=0.00009) or asthma (16.67%, p=0.0139). The HH inter-observer κ agreement was substantial in IPF (κ=0.78) and asthma (κ=0.86), and moderate in COPD (κ=0.42). In IPF, HH did not correlate with lung function, except in those on anti-reflux therapy, who had a betterDL,CO(p<0.03) and CPI (p<0.04). HH correlated with GOR as measured by DeMeester scores (p<0.04).

HH is more common in IPF than COPD or asthma. In an IPF cohort, HH correlated with higher DeMeester scores, confirming abnormal acid GOR. Presence of HH alone was not associated with decreased lung function.