bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining the Matthew effect on the motivation and ability to stay at work after heart disease
Authors: Meland Eivind , Grønhaug Siri , Øystese Kristin , Mildestvedt Thomas
Published: February 2011

Aims: Cardiac rehabilitation should safeguard that socioeconomic factors or other differences that affect people’s cardiovascular health are not further aggravated after healthcare treatment. The study examines whether socioeconomic status, emotional problems, or the severity of disease affect people’s ability to continue to work after heart disease. We also examined if these effects can be explained by differences in motivational factors. Methods: 217 patients (41 women) from the Krokeide Rehabilitation Centre in Bergen participated. Multiple linear regression analysis was used to examine motivational differences, and logistic regression analysis was used to examine whether socioeconomic factors or other differences affected people’s ability to continue to work after heart disease. Results: Self-efficacy for future work strongly impacted the likelihood of being incapacitated for work during the 2-year follow-up. The household’s total income and emotional problems were statistically significant related to patients dropping out from work in the course of the observation. The association between emotional problems and future work was mediated by motivational problems. The relation between income and future incapacity for work could not be explained by motivational factors. Conclusions: The study shows a clear Matthew effect on people’s ability to continue to work after heart disease as low-income groups and people with emotional problems are more at risk of dropping out of work. This Matthew effect was, however, only explained by the motivational difficulties for the association between emotional distress and dropping out of work and not for the impact of household income on the likelihood of leaving work.
The sense of being seen: Ocular effects at Sutton Hoo
Authors: Williams Howard
Published: February 2011

I consider the mnemonic agency of the art adorning a diverse range of artefacts interred in one of Europe’s most famous archaeological discoveries. The early seventh-century AD burial chamber constructed within a ship beneath Mound 1 at Sutton Hoo, Suffolk, UK, was uncovered in 1939. I identify a theme linking the prestige artefacts placed within this ‘princely’ grave: many are covered with eyes or eye-like forms. I argue that this ocular quality to the art — not simply visually striking but affording the sense of animated, watching presences — was integral to the selection of artefacts for burial. I argue that the beastly, monstrous and humanoid eyes commemorated the dead person as all-seeing. Those witnessing the staged wrapping and consignment of the artefacts were afforded the sense of being all-seen. By exploring art in this elite mortuary context, the article presents a case study in the early medieval archaeology of the senses.
Peace maintenance and political messages: The significance of walls during and after the Northern Irish ‘Troubles’
Authors: McAtackney Laura
Published: February 2011

The role of wall murals — as both territorial markers and as a means of maintaining and reinforcing identity — has been a frequent subject of study as a way of understanding the recent conflict in Northern Ireland, euphemistically known as ‘the Troubles’ (c. 1969—c. 1998). Whilst the heightened political and social relevance of murals and graffiti during civil conflict is undoubtedly a worthy subject of study, the role of their physical context — walls — has not been so thoroughly analysed and deconstructed. In the context of Northern Ireland, walls have had multiple uses and meanings — they can be not only blank canvases to facilitate communication but also physical barriers that solidify social relations and prevent interaction. This article examines the dual role of walls both during and in the aftermath of conflict as a means of highlighting their positive and negative attributes and de-essentializing their existence. It is suggested that there is a need to contextualize and consider the current and potential role of walls in the maintenance of peace and facilitating a ‘new’ Northern Ireland.
The influence of immigration status on early childhood education and care enrollment
Authors: Pastan Greenberg Joy , Kahn Jessica M.
Published: February 2011

Early childhood education and care has become the norm for children in the United States and most European countries. In the United States, immigrant children, a growing demographic, are under-enrolled, particularly in formal settings. This research revealed that younger children of immigrant mothers were less likely to be in non-parental care, but immigrant status did not affect enrollment of three—five-year-old children when various parental and child characteristics were controlled. Socio-economic factors were more important predictors of early childhood education and care use than immigrant status in the older group, which suggests that policies aimed at increasing enrollment among immigrants must consider the primacy of these variables.
The long term effects of early acquired skills and behaviors on young children’s achievement in literacy and mathematics
Authors: Bodovski Katerina , Youn Min-Jong
Published: February 2011

Using the recently available wave of a large nationally representative sample of American elementary school children (ECLS-K data), this study examined the relationship between 6-7 year old students’ behaviors exhibited in the 1st grade (approaches to learning, interpersonal skills, externalizing and internalizing behavior) and their reading and mathematics achievement at the end of the 5th grade (pupils aged 10 - 11 years), controlling for their achievement in the 1st grade. Findings include the single behavioral dimension that has a substantial association with later achievement is students’ approaches to learning. The analysis of the interaction effects showed that students from families of low socioeconomic status, girls (in case of math) and minority students were more likely to have higher test scores given their improved approaches to learning. Further, the results demonstrated that basic skills (math and reading in the 1st grade) are substantial predictors of the 5th-grade approaches to learning. The findings reveal the complexity of the intertwined relationship between cognitive and behavior outcomes among young students and the long-term effects of early acquired skills and behaviors.
Lexical input to young children from extremely poor communities in Argentina: Effects of a home literacy program
Authors: Renata Rosemberg Celia , Stein Alejandra , Borzone Ana María
Published: February 2011

The study analyzes the lexical properties of the linguistic context that children from marginalized urban neighborhoods from Buenos Aires, Argentina, are exposed to in the literacy situations generated by an at-home early literacy program. The analysis is focused on the comparison of the vocabulary that these children are exposed to daily with the characteristics of the lexical surround in the literacy settings induced by the implementation of the program. Results showed that literacy situations provided children with an enriched lexical input: a higher amount of word tokens and word types, and more unfamiliar words that represented phenomena, properties or actions not directly observable.
Harmonic analysis of some light sources used for domestic lighting
Authors: Majithia CA , Desai AV , Panchal AK
Published: February 2011

Measurements of voltage and current waveforms produced by a variety of light sources used for domestic lighting are presented. Incandescent, halogen, compact fluorescent, linear tubular fluorescent (with a magnetic choke and with an electronic ballast) and two forms of light emitting diode (LED) lamps were measured. From the voltage and current waveforms measured, the total harmonic distortion (THD), distortion and displacement power factors (PFs) and the net PF are estimated for the different lamp types. This analysis suggests that compact fluorescent and LED lamps may exhibit high levels of THD due to their spiky current waveforms.
The Ecology of Virtual Human Resource Development
Authors: Bennett Elisabeth E. , Bierema Laura L.
Published: February 2011

This article explores the ecology of virtual human resource development (VHRD). It argues VHRD can be conceptualized as a subset of Virtual HR, and thus, requires strategic integration, adaptation, and attention to the interrelations within the system to promote a healthy ecology. VHRD is a powerful combination of people and technology, presenting not only opportunities for learning and innovation but also the need for critique. VHRD is driving a paradigm shift in the field of HRD, necessitating new skills, policies, and new theories that explain phenomena in virtual environments.
Harnessing and Optimal Utilization of Human Capital in Virtual Workplace Environments
Authors: Nafukho Fredrick M. , Graham Carroll M. , Muyia Helen Machuma A.
Published: February 2011

The primary purpose of this article is to demonstrate the role of virtual human resource development (VHRD) in promoting optimal utilization of human capital in virtual workplace settings currently characterized by millennial generation who surf the Internet, Tweet, talk, listen to iTunes, and text-message while working. To achieve the objective of the article, selected review of literature was conducted. The article defines human capital and demonstrates how technology can be positively used to promote virtual learning, workplace learning, and eventually lead to performance improvement in the workforce. Also discussed are the challenges of using Virtual HRD and implications for HRD theory, research, and practice.
The Coming Paradigm Shift: Synthesis and Future Directions for Virtual HRD
Authors: Bennett Elisabeth E.
Published: February 2011

Virtual human resource development (VHRD) is beginning to be viewed in other fields as the next generation of knowledge management. This article synthesizes the discussions of the contributing authors for this issue of Advances, describes future trends, and serves as a call to the field of HRD to develop and study VHRD. VHRD symbolizes a paradigm shift that will grow in a chaotic fashion at first as it integrates with present practices and systems, but it will become increasingly central to organizational life because of its ability to foster creativity and maximize knowledge flow. This article presents a heuristic for transferring learning that occurs in virtual environments outside organizational boundaries to professional work and organizational processes. Future directions for research and practice in VHRD include new roles for HRD professionals, particularly that of architects of virtual learning environments, the need to build theory for VHRD and to study the impact of new technologies.
Exploring the Emergence of Virtual Human Resource Development
Authors: McWhorter Rochell R.
Published: February 2011

Technology is permeating our personal and professional lives and is having an enormous impact on the field of human resource development (HRD). Given the growing interest that scholars have had for integrating technology into HRD practice and research, Virtual HRD (VHRD) has emerged as a new area of inquiry in the field of HRD. This article begins by defining and exploring the emergence of the construct of VHRD. It reviews the evolution of technology from the inception of the Academy of Human Resource Development and integrates selected literature that supports the emergence of VHRD in the field of HRD to include sophisticated, immersive environments appropriate for HRD practice. This article then introduces the contents of this special issue and articulates the four-part format that will be used to do so. Lastly, a summary is provided that serves as a call to action for HRD scholars and practitioners to more thoughtfully consider the impact of VHRD on the future of the HRD field, to disseminate the accumulated research that has been done thus far, as well as to promote awareness of VHRD as a compelling HRD construct before other fields lay claim to this territory and obfuscate the contributions that have already been made toward understanding, defining, and researching this emergent construct.
A Study of Adult Learning in a Virtual World
Authors: Mancuso Donna S. , Chlup Dominique T. , McWhorter Rochell R.
Published: February 2011

It is crucial that employees and students become astute adult learners. Due to rapidly changing technology in both the workplace and instructional venues, organizations are challenged to find new and useful tools for adapting to these advances in both content and processes of work. Therefore, understanding how virtual worlds function as sites of adult learning (including enablers and barriers to successful adult learning experiences) becomes an important task for developing the construct of virtual human resource development (VHRD). In this empirical exploratory study, adult learning was conducted within the virtual world of Second Life (SL), both for its popularity and afforded opportunities for collaboration. The findings in this study indicate there are important enablers and barriers for adult learning in this virtual world that may prove useful for HRD professionals when designing learning experiences in virtual environments.
Eliminating Inequities in Health Care
Authors: Havens Betsy E. , Yonas Michael A. , Mason Mondi A. , Eng Eugenia , Farrar Vanessa D.
Published: February 2011

Antiracism training for staff of health care institutions is a promising intervention strategy to address racial and ethnic disparities in health care. In 2001, Southern County Public Health Department (SCPHD) staff completed a mandatory Dismantling Racism (DR) training, and some continued with an optional DR process to challenge institutional racism within their agency. To explore factors influencing participation in optional DR activities (i.e., caucuses and Change Team), a process evaluation was conducted involving in-depth interviews with 28 SCPHD administrators and staff members, whose participation in the DR process varied. Findings demonstrate that familiarity with and receptiveness to the relationship between racism and health care inequities influenced participation in DR activities. Perceived relevance and impact of the DR process on the organization and staff were also major factors affecting participation. Improvements for implementing such efforts including the consideration of institutional power and other implications for addressing racial health care inequities through antiracism initiatives are discussed.
Identifying the People and Factors That Influence Children’s Intentions to Make Lifestyle Changes
Authors: Cottrell Lesley , Harris Carole V. , Bradlyn Andrew , Gunel Erdogan , Neal William A. , Abildso Laurie , Coffman Jessica Wrye
Published: February 2011

Childhood obesity and health behavior programs are increasingly a focus within literature and individual provider practices. This study was designed to inform “best practices” for establishing effective programs in the medical setting by identifying persons and factors that influence children’s willingness to be active, eat healthy, and lose weight when medically appropriate. A total of 342 child and parent dyads living in a rural setting participated in this study. Child and parent report of theory of planned behavior constructs and child intentions to lose weight, eat healthier, and increase own exercise was established as the study outcomes. Parent and child perceptions and child characteristics (e.g., weight status) were associated with children’s intentions to lose weight and obtain more exercise whereas only child perceptions were associated with children’s intentions to eat healthier. Incorporating children as young as 10 years of age in conversations and planning for diet and physical activity lifestyle changes is essential for the success of the treatment option.
Movement Observation Activates Lower Limb Motor Networks in Chronic Complete Paraplegia
Authors: Hotz-Boendermaker Sabina , Hepp-Reymond Marie-Claude , Curt Armin , Kollias Spyros S.
Published: February 2011

Background. In healthy subjects, observation of actions activates a motor network similar to that involved in the performance of the observed actions. Movement observation could perhaps be applied to functionally sustain brain motor functions when efferent motor commands and proprioceptive feedbacks are disconnected. Objective. The authors examined whether observation-induced brain activation is preserved in people with chronic complete spinal cord injury (SCI). Methods. Nine patients and 12 healthy subjects underwent behavioral assessment and functional magnetic resonance imaging. The SCI patients attempted to perform dorsal and plantar flexions of the right foot, and the controls also executed the same movement. Both groups observed subsequent video clips showing the same movement. Results. In the SCI group, attempted and observed foot movements activated a common observation–execution network including ventral premotor, parietal cortex, and cerebellum as in healthy subjects. Conclusions. Long after onset of complete SCI, the brain maintains its ability to respond to task-specific visual inputs, which suggests preservation of motor programs. This persistence might be a prerequisite for repair strategies of the spinal cord that rely on appropriate activation of the brain to try to restore limb function. The preserved cortical network may offer an additional motor rehabilitation approach for people with SCI.
Rehabilitation Promotes Recovery After Whole Blood–Induced Intracerebral Hemorrhage in Rats
Authors: MacLellan Crystal L. , Plummer Nita , Silasi Gergely , Auriat Angela M. , Colbourne Frederick
Published: February 2011

Background. Rehabilitation improves recovery after intracerebral hemorrhage (ICH) caused by collagenase infusion into the striatum of rats by promoting dendritic growth and reducing brain injury in this model. Objective. Effective preclinical testing requires multiple models because none, including the collagenase model, perfectly mimics human ICH. Thus, the authors assessed enhanced rehabilitation (ER), a combination of environmental enrichment and task-specific motor training, on skilled reaching, lesion size, and dendritic plasticity after whole blood–induced, striatal ICH. Methods. Three groups of rats were trained to retrieve food in a reaching task prior to ICH. One group was euthanized at 7 days, whereas 2 groups survived 7 weeks post-ICH. Of the latter, 1 group received 2 weeks of ER starting at 7 days, whereas controls did not. Reaching success was assessed 6 weeks after ICH. Lesion volume and dendritic length and complexity (contralateral striatum) were assessed. Results. The ICH caused reaching deficits that were markedly attenuated by ER as observed previously in the collagenase model. In contrast to that model, there was a time-dependent decline in dendritic length after untreated, whole blood–induced ICH. Furthermore, behavioral recovery was not accompanied by changes in lesion volume or contralateral dendritic morphology. Conclusions. Converging data from animal models support the use of rehabilitation for ICH patients. However, although rehabilitation effectively promotes behavioral recovery, the mechanisms of action vary by model making it difficult to predict clinical effects.
Brain and Spinal Cord Interaction
Authors: Wu Aiguo , Ying Zhe , Schubert David , Gomez-Pinilla Fernando
Published: February 2011

Background. In addition to cognitive dysfunction, locomotor deficits are prevalent in traumatic brain injured (TBI) patients; however, it is unclear how a concussive injury can affect spinal cord centers. Moreover, there are no current efficient treatments that can counteract the broad pathology associated with TBI. Objective. The authors have investigated potential molecular basis for the disruptive effects of TBI on spinal cord and hippocampus and the neuroprotection of a curcumin derivative to reduce the effects of experimental TBI. Methods. The authors performed fluid percussion injury (FPI) and then rats were exposed to dietary supplementation of the curcumin derivative (CNB-001; 500 ppm). The curry spice curcumin has protective capacity in animal models of neurodegenerative diseases, and the curcumin derivative has enhanced brain absorption and biological activity. Results. The results show that FPI in rats, in addition to reducing learning ability, reduced locomotor performance. Behavioral deficits were accompanied by reductions in molecular systems important for synaptic plasticity underlying behavioral plasticity in the brain and spinal cord. The post-TBI dietary supplementation of the curcumin derivative normalized levels of BDNF, and its downstream effectors on synaptic plasticity (CREB, synapsin I) and neuronal signaling (CaMKII), as well as levels of oxidative stress–related molecules (SOD, Sir2). Conclusions. These studies define a mechanism by which TBI can compromise centers related to cognitive processing and locomotion. The findings also show the influence of the curcumin derivative on synaptic plasticity events in the brain and spinal cord and emphasize the therapeutic potential of this noninvasive dietary intervention for TBI.
Modeling the “Minimally Invasive Surgery Effect” in Total Joint Replacement
Authors: Vavken Patrick , Dorotka Ronald
Published: February 2011

Introduction. A beneficial effect of minimally invasive surgery (MIS) in total joint replacement has been postulated, but to date it still remains to be proven. This study aimed at assessing what the common effects of MIS are in all clinical trials/studies. Methods. Randomized controlled trials of MIS total joint replacement were searched online in Medline, EMBASE, CINAHL, and the Cochrane Library. Data on clinical endpoints were extracted in duplicate. Results. The authors pooled data from 13 studies and found beneficial “MIS effects” for most endpoints. Blood loss, clinical scores, and incision length were significantly different from the standard procedure. The calculated MIS effect could be successfully validated using 3 independent data sets. Conclusion. Our analysis provides strong evidence for an intrinsic “MIS effect” in total joint replacement. However, most effect sizes seem too small to have much clinical meaning.
The Gender of Criminal Opportunity: The Impact of Male Co-Offenders on Women’s Crime
Authors: Becker Sarah , McCorkel Jill A.
Published: February 2011

Women commit less crime than men and their crimes are typically less serious, violent, and profitable. Most investigations of this “gender gap” in offending consider differences in social control or socialization. This helps explain overall crime participation disparities, but cannot account for the sex-segregated character of offending. Building on ethnographic research and feminist labor market analyses, our study explores how gender affects access to criminal opportunities. Using NIBRS data, we examine the effect a male co-offender has on women’s offending. We find that the presence of a male co-offender broadens women’s criminal involvement in distinctive ways.
Gendered Organizations: Challenges for Domestic Violence Victim Advocates and Feminist Advocacy
Authors: Nichols Andrea J.
Published: February 2011

Acker’s theory of gendered organizations serves as an important theoretical lens for researching the gendered processes of domestic violence organizations. Specifically, I document challenges presented to domestic violence victim advocates as a result of gendered processes in community based responses to domestic violence and offer specific policy suggestions for future collaborations between stakeholders in combating domestic violence.
Unintentional injury among low-income 5-year-olds with chronic health conditions
Authors: Schwebel David C , Brezausek Carl M
Published: February 2011

Background: Growing numbers of children suffer from chronic health conditions, and initial evidence suggests chronic illness may be associated with increased child injury risk. We examined injury risk among 5-year-olds with and without chronic health conditions.

Methods: Data from a diverse US sample of 7954 low-income 5-year-olds participating in the National Head Start/Public School Early Childhood Transition Demonstration Study were analysed. Mothers reported demographics, presence/absence of eight chronic health conditions, and whether children had experienced injuries requiring professional medical attention in the past year. Primary analyses used ordinal logistic regression.

Results: Asthma, bronchitis, recurrent ear infections, hay fever/allergies and speech problems associated with increased injury risk (OR range = 1.20—1.49 in bivariate ordinal logistic regression, ps < 0.01). Children with cerebral palsy had reduced injury risk (OR = 0.37, 95% CI = 0.15—0.91, p < 0.05). Most findings held after including demographic covariates in multivariate models.

Conclusion: Because a range of chronic health conditions associated with increased injury risk, the causal mechanism behind relations between chronic illness and injury risk may not be disease-specific. Instead, factors related to having chronic medical conditions—not any particular condition—might contribute. Possible mediators include impaired family functioning, impaired peer relations, and familiarity with the health system/health-seeking behaviours.
Probiotics in the prevention of antibiotic-associated diarrhoea and Clostridium difficile infection
Authors: Hickson Mary
Published: February 2011

Diarrhoea, as a common side effect of antibiotics, increases treatment costs and length of stay in acute healthcare facilities. One potential strategy to prevent this side effect is the concurrent use of probiotic bacteria or yeast. This review discusses the evidence for the efficacy of probiotics in the prevention of antibiotic-associated diarrhoea and Clostridium difficile infection; the potential mechanisms by which probiotics may work; their safety; what future research is required; and recommendations for use in clinical practice.
Dimensions of Brand Equity in the Chain Restaurant Industry
Authors: Sean Hyun Sunghyup , Kim Wansoo
Published: February 2011

Four of the dimensions that combine to contribute to chain restaurants’ brand equity are brand awareness, brand image, perceived quality, and brand loyalty. A test of a structural model connecting these four attributes of brand equity was based on data collected from 188 patrons of five chain restaurant brands in Korea. The resulting data analysis demonstrates that the four dimensions of brand equity are interrelated. The model indicates that the foundation of brand equity is brand awareness. However, while brand awareness influences brand loyalty formation, its impact is mediated by the effects of brand image and perceived quality. In addition, although brand awareness is a prerequisite of brand loyalty, brand image and perceived quality bear a stronger impact on the development of brand loyalty. On balance, the implications of these findings support the restaurant industry’s practices of constant promotion, quality assurance, and process improvement.
Opportunism in Brand Partnerships
Authors: Dev Chekitan S. , Grzeskowiak Stephan , Brown James R.
Published: February 2011

Brand partner opportunism—deceptive or guileful behavior to gain an advantage—is a threat to a successful brand partnership. In this study, the authors examined the effects of coercive and noncoercive tactics for preventing opportunism as those tactics are influenced by relational norms—mutually held standards of behavior that support close relationships. In a survey of 367 hotel general managers from two large hotel brands, the authors found that, in partnerships characterized by strong relational norms, coercive influence strategies, such as threats, promises, or legalistic pleas, are less effective at limiting opportunism than are noncoercive strategies, such as information exchange, recommendations, or requests, which are more effective. In contrast, when relational norms are weak, the authors found that coercive strategies are more effective than are noncoercive strategies. However, regardless of the nature of the relationship, the GMs reported that coercive techniques work only briefly and are ineffective over the long term. Thus, considering the nature of the hotel industry, noncoercive strategies are more likely to benefit brand headquarters’ efforts to limit brand partner opportunism.
In vitro generation of HSC-like cells from murine ESCs/iPSCs by enforced expression of LIM-homeobox transcription factor Lhx2
Authors: Kitajima Kenji , Minehata Ken-ichi , Sakimura Kenji , Nakano Toru , Hara Takahiko
Published: February 2011

Identification of genes involved in in vitro differentiation induction of embryonic stem cells (ESCs) into hematopoietic stem cells (HSCs) has been challenged during last decade. To date, a homeobox transcription factor Hoxb4 has been only demonstrated to possess such an effect in mice. Here, we show that HSC-like cells were efficiently induced from mouse ESCs by enforced expression of Lhx2, a LIM-homeobox transcription factor. Transduction of Lhx2 into ESC-derived mesodermal cells resulted in robust differentiation of c-Kit+/Sca-1+/Lineage− (KSL) cells in vitro. The KSL cell induction frequency was superior to the case of Hoxb4. Furthermore, transplantation of Lhx2-transduced hematopoietic cells into lethally irradiated mice resulted in multilineage repopulation of hematopoietic cells over 4 months. Transduction of Lhx2 into induced pluripotent stem cells (iPSCs) was also effective in generating KSL cells in vitro, as well as HSC-like activities in vivo. These results demonstrate that ectopic expression of Lhx2 confers an in vivo engrafting capacity to ESC/iPSC-derived hematopoietic cells and in vivo behavior of iPSC-derived hematopoietic cells is almost identical to that of ESC-derived cells.
Prdm16 is a physiologic regulator of hematopoietic stem cells
Authors: Aguilo Francesca , Avagyan Serine , Labar Amy , Sevilla Ana , Lee Dung-Fang , Kumar Parameet , Lemischka Ihor R. , Zhou Betty Y. , Snoeck Hans-Willem
Published: February 2011

Fetal liver and adult bone marrow hematopoietic stem cells (HSCs) renew or differentiate into committed progenitors to generate all blood cells. PRDM16 is involved in human leukemic translocations and is expressed highly in some karyotypically normal acute myeloblastic leukemias. As many genes involved in leukemogenic fusions play a role in normal hematopoiesis, we analyzed the role of Prdm16 in the biology of HSCs using Prdm16-deficient mice. We show here that, within the hematopoietic system, Prdm16 is expressed very selectively in the earliest stem and progenitor compartments, and, consistent with this expression pattern, is critical for the establishment and maintenance of the HSC pool during development and after transplantation. Prdm16 deletion enhances apoptosis and cycling of HSCs. Expression analysis revealed that Prdm16 regulates a remarkable number of genes that, based on knockout models, both enhance and suppress HSC function, and affect quiescence, cell cycling, renewal, differentiation, and apoptosis to various extents. These data suggest that Prdm16 may be a critical node in a network that contains negative and positive feedback loops and integrates HSC renewal, quiescence, apoptosis, and differentiation.
Evaluation of the profibrinolytic properties of an anti-TAFI monoclonal antibody in a mouse thromboembolism model
Authors: Vercauteren Ellen , Emmerechts Jan , Peeters Miet , Hoylaerts Marc F. , Declerck Paul J. , Gils Ann
Published: February 2011

The enhancement of fibrinolysis constitutes a promising approach to treat thrombotic diseases. Activated thrombin activatable fibrinolysis inhibitor (TAFIa) attenuates fibrinolysis and is an attractive target to develop profibrinolytic drugs. TAFI can be activated by thrombin, thrombin/thrombomodulin, or plasmin, but the in vivo physiologic TAFI activator(s) are unknown. Here, we generated and characterized MA-TCK26D6, a monoclonal antibody raised against human TAFI, and examined its profibrinolytic properties in vitro and in vivo. In vitro, MA-TCK26D6 showed a strong profibrinolytic effect caused by inhibition of the plasmin-mediated TAFI activation. In vivo, MA-TCK26D6 significantly decreased fibrin deposition in the lungs of thromboembolism-induced mice. Moreover, in the presence of MA-TCK26D6, plasmin-α2-antiplasmin complexes in plasma of thromboembolism-induced mice were significantly increased compared with a control antibody, indicative of an acceleration of fibrinolysis through MA-TCK26D6. In this study, we show that plasmin is an important TAFI activator that hampers in vitro clot lysis. Furthermore, this is the first report on an anti-TAFI monoclonal antibody that demonstrates a strong profibrinolytic effect in a mouse thromboembolism model.
Family psychoeducation for major depression: randomised
controlled trial
Authors: Shimazu Kae , Shimodera Shinji , Mino Yoshio , Nishida Atsushi , Kamimura Naoto , Sawada Ken , Fujita Hirokazu , Furukawa Toshi A. , Inoue Shimpei
Published: February 2011

Background

The value of family psychoeducation for schizophrenia has been well
established, and indications for its use have recently expanded to
include bipolar affective disorder. However, no study to date has
adequately examined its use in depression.

Aims

To examine family psychoeducation in the maintenance treatment of
depression and to investigate the influence of the family's expressed
emotion (EE) on its effectiveness.

Method

Of 103 patients diagnosed with major depression and their primary family
members, 57 pairs provided written informed consent. The pairs were
randomly allocated to the intervention (n = 25) or
control (n = 32). One family in the intervention group
and two in the control group withdrew their consent after randomisation.
The intervention group underwent four psychoeducation sessions consisting
of didactic lectures about depression and group problem-solving focusing
on how to cope in high-EE situations. Patients did not attend these
sessions. Patients in both the intervention and control groups received
treatment as usual. The families' EE levels were evaluated through
Five-Minute Speech Samples. The primary outcome was relapse.

Results

Time to relapse was statistically significantly longer in the
psychoeducation group than in the control group (Kaplan–Meier survival
analysis, P = 0.002). The relapse rates up to the
9-month follow-up were 8% and 50% respectively (risk ratio 0.17, 95% CI
0.04–0.66; number needed to treat 2.4, 95% CI 1.6–4.9). In Cox
proportional hazard analysis, baseline EE did not moderate the
effectiveness of the intervention.

Conclusions

Family psychoeducation is effective in the prevention of relapse in adult
patients with major depression.
Prevalence of autoimmune thyroid dysfunction in postpartum psychosis
Authors: Bergink Veerle , Kushner Steven A. , Pop Victor , Kuijpens Hans , Lambregtse-van den Berg Mijke P. , Drexhage Roos C. , Wiersinga Wilmar , Nolen Willem A. , Drexhage Hemmo A.
Published: February 2011

Background

Postpartum psychosis is a life-threatening psychiatric emergency, which often occurs without significant premorbid symptoms. Although many studies have postulated an involvement of the immune and endocrine systems in the onset of postpartum psychosis, the specific aetiological factors have remained unknown.

Aims

To examine the hypothesis that autoimmune thyroid dysfunction may be associated with the onset of postpartum psychosis.

Method

Thirty-one consecutive primiparous women with no prior psychiatric history were referred to our in-patient unit for postpartum psychosis. The control group (n = 117) comprised primiparous women with consecutive deliveries at a community practice. Blood samples were obtained from all participants at 4 weeks and 9 months postpartum. Thyroperoxidase antibody levels were quantified as immunological measures of autoimmune thyroid disease (AITD). Thyroid-stimulating hormone and free thyroxine levels were measured to assess clinical thyroid dysfunction.

Results

At 4 weeks postpartum and prior to the initiation of mood stabiliser therapy, 19% of women with postpartum psychosis had AITD compared with only 5% in the control group. Women with both postpartum psychosis and AITD had a dramatically higher risk of progression to clinical thyroid dysfunction (67%) than control participants with AITD (20%).

Conclusions

Women with postpartum psychosis are at higher risk not only of AITD but also of clinical thyroid failure. These data implicate thyroid function as an important clinical outcome in patients with postpartum psychosis. Further, AITD represents a potentially strong aetiological factor for the development of postpartum psychosis. Therefore, screening for thyroperoxidase antibodies is warranted in patients with postpartum psychosis.
RUNX1 Mutations in Acute Myeloid Leukemia: Results From a Comprehensive Genetic and Clinical Analysis From the AML Study Group
Authors: Gaidzik Verena I. , Bullinger Lars , Schlenk Richard F. , Zimmermann Andreas S. , Röck Jürgen , Paschka Peter , Corbacioglu Andrea , Krauter Jürgen , Schlegelberger Brigitte , Ganser Arnold , Späth Daniela , Kündgen Andrea , Schmidt-Wolf Ingo G.H. , Götze Katharina , Nachbaur David , Pfreundschuh Michael , Horst Heinz A. , Döhner Hartmut , Döhner Konstanze
Published: February 2011

Purpose

To evaluate frequency, biologic features, and clinical relevance of RUNX1 mutations in acute myeloid leukemia (AML).

Patients and Methods

Diagnostic samples from 945 patients (age 18 to 60 years) were analyzed for RUNX1 mutations. In a subset of cases (n = 269), microarray gene expression analysis was performed.

Results

Fifty-nine RUNX1 mutations were identified in 53 (5.6%) of 945 cases, predominantly in exons 3 (n = 11), 4 (n = 10), and 8 (n = 23). RUNX1 mutations clustered in the intermediate-risk cytogenetic group (46 of 640, 7.2%; cytogenetically normal, 34 of 538, 6.3%), whereas they were less frequent in adverse-risk cytogenetics (five of 109, 4.6%) and absent in core-binding-factor AML (0 of 77) and acute promyelocytic leukemia (0 of 61). RUNX1 mutations were associated with MLL-partial tandem duplications (P = .0007) and IDH1/IDH2 mutations (P = .03), inversely correlated with NPM1 (P < .0001), and in trend with CEBPA (P = .10) mutations. RUNX1 mutations were characterized by a distinct gene expression pattern; this RUNX1 mutation-derived signature was not exclusive for the mutation, but also included mostly adverse-risk AML [eg, 7q-, -7, inv(3), or t(3;3)]. RUNX1 mutations predicted for resistance to chemotherapy (rates of refractory disease 30% and 19%, P = .047, for RUNX1-mutated and wild-type patients, respectively), as well as inferior event-free survival (EFS; P < .0001), relapse-free survival (RFS, P = .022), and overall survival (P = .051). In multivariable analysis, RUNX1 mutations were an independent prognostic marker for shorter EFS (P = .007). Explorative subgroup analysis revealed that allogeneic hematopoietic stem-cell transplantation had a favorable impact on RFS in RUNX1-mutated patients (P < .0001).

Conclusion

AML with RUNX1 mutations are characterized by distinct genetic properties and are associated with resistance to therapy and inferior outcome.
Randomized, Double-Blind Study of Denosumab Versus Zoledronic Acid in the Treatment of Bone Metastases in Patients With Advanced Cancer (Excluding Breast and Prostate Cancer) or Multiple Myeloma
Authors: Henry David H. , Costa Luis , Goldwasser Francois , Hirsh Vera , Hungria Vania , Prausova Jana , Scagliotti Giorgio Vittorio , Sleeboom Harm , Spencer Andrew , Vadhan-Raj Saroj , von Moos Roger , Willenbacher Wolfgang , Woll Penella J. , Wang Jianming , Jiang Qi , Jun Susie , Dansey Roger , Yeh Howard
Published: February 2011

Purpose

This study compared denosumab, a fully human monoclonal anti-receptor activator of nuclear factor kappa-B ligand antibody, with zoledronic acid (ZA) for delaying or preventing skeletal-related events (SRE) in patients with advanced cancer and bone metastases (excluding breast and prostate) or myeloma.

Patients and Methods

Eligible patients were randomly assigned in a double-blind, double-dummy design to receive monthly subcutaneous denosumab 120 mg (n = 886) or intravenous ZA 4 mg (dose adjusted for renal impairment; n = 890). Daily supplemental calcium and vitamin D were strongly recommended. The primary end point was time to first on-study SRE (pathologic fracture, radiation or surgery to bone, or spinal cord compression).

Results

Denosumab was noninferior to ZA in delaying time to first on-study SRE (hazard ratio, 0.84; 95% CI, 0.71 to 0.98; P = .0007). Although directionally favorable, denosumab was not statistically superior to ZA in delaying time to first on-study SRE (P = .03 unadjusted; P = .06 adjusted for multiplicity) or time to first-and-subsequent (multiple) SRE (rate ratio, 0.90; 95% CI, 0.77 to 1.04; P = .14). Overall survival and disease progression were similar between groups. Hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred at similarly low rates in both groups. Acute-phase reactions after the first dose occurred more frequently with ZA, as did renal adverse events and elevations in serum creatinine based on National Cancer Institute Common Toxicity Criteria for Adverse Events grading.

Conclusion

Denosumab was noninferior (trending to superiority) to ZA in preventing or delaying first on-study SRE in patients with advanced cancer metastatic to bone or myeloma. Denosumab represents a potential novel treatment option with the convenience of subcutaneous administration and no requirement for renal monitoring or dose adjustment.
DNA Methylation Array Analysis Identifies Profiles of Blood-Derived DNA Methylation Associated With Bladder Cancer
Authors: Marsit Carmen J. , Koestler Devin C. , Christensen Brock C. , Karagas Margaret R. , Houseman E. Andres , Kelsey Karl T.
Published: February 2011

Purpose

Epigenetic alterations in tissues targeted for cancer play a causal role in carcinogenesis. Changes in DNA methylation in nontarget tissues, specifically peripheral blood, can also affect risk of malignant disease. We sought to identify specific profiles of DNA methylation in peripheral blood that are associated with bladder cancer risk and therefore serve as an epigenetic marker of disease susceptibility.

Methods

We performed genome-wide DNA methylation profiling on participants involved in a population-based incident case-control study of bladder cancer.

Results

In a training set of 112 cases and 118 controls, we identified a panel of 9 CpG loci whose profile of DNA methylation was significantly associated with bladder cancer in a masked, independent testing series of 111 cases and 119 controls (P < .0001). Membership in three of the most methylated classes was associated with a 5.2-fold increased risk of bladder cancer (95% CI, 2.8 to 9.7), and a model that included the methylation classification, participant age, sex, smoking status, and family history of bladder cancer was a significant predictor of bladder cancer (area under the curve, 0.76; 95% CI, 0.70 to 0.82). CpG loci associated with bladder cancer and aging had neighboring sequences enriched for transcription-factor binding sites related to immune modulation and forkhead family members.

Conclusion

These results indicate that profiles of epigenetic states in blood are associated with risk of bladder cancer and signal the potential utility of epigenetic profiles in peripheral blood as novel markers of susceptibility to this and other malignancies.
Prognostic and Clinicopathologic Associations of Oncogenic BRAF in Metastatic Melanoma
Authors: Long Georgina V. , Menzies Alexander M. , Nagrial Adnan M. , Haydu Lauren E. , Hamilton Anne L. , Mann Graham J. , Hughes T. Michael , Thompson John F. , Scolyer Richard A. , Kefford Richard F.
Published: February 2011

Purpose

To assess the frequency and type of oncogenic BRAF mutations in metastatic melanoma and correlate BRAF status with clinicopathologic features and outcome.

Patients and Methods

Consecutive BRAF-tested Australian patients with metastatic melanoma (n = 197) were observed prospectively. A comprehensive range of clinicopathologic variables were correlated with BRAF mutation status, and a survival analysis was conducted.

Results

Forty-eight percent of patients had a BRAF mutation; 70 patients (74%) had V600E, 19 (20%) had V600K, and six (6%) had other genotypes. Other than age at diagnosis of distant metastasis (median age, 56 v 63 years for BRAF-mutant v BRAF wild-type patients, respectively; P < .001), there was no significant difference in clinical features of patients with metastatic melanoma by mutation status. Features of the antecedent primary melanoma significantly associated with a BRAF mutation (P < .05) were histopathologic subtype, presence of mitoses, single or occult primary melanoma, truncal location, and age at diagnosis of primary tumor ≤ 50 years. The interval from diagnosis of first-ever melanoma to distant metastasis was not significantly different between BRAF-mutant and BRAF wild-type patients; however, the median survival of patients with newly diagnosed metastatic melanoma was 5.7 months for BRAF-mutant patients not treated with a BRAF inhibitor, 8.5 months for BRAF wild-type patients, and not reached for BRAF-mutant patients treated with a BRAF inhibitor.

Conclusion

V600K mutations comprised 20% of BRAF mutations. Characteristics of the antecedent primary melanoma and age at diagnosis differed in BRAF-mutant and BRAF wild-type patients. The presence of mutant BRAF had no impact on the disease-free interval from diagnosis of first-ever melanoma to first distant metastasis; however, it may have impacted survival thereafter.
Can Patient-Reported Outcome Measures Identify Cancer Patients' Most Bothersome Issues?
Authors: Snyder Claire F. , Blackford Amanda L. , Aaronson Neil K. , Detmar Symone B. , Carducci Michael A. , Brundage Michael D. , Wu Albert W.
Published: February 2011

Purpose

Patient-reported outcome (PRO) questionnaires are being investigated for their ability to aid in individual patient management. We evaluated whether PROs can identify patients' most bothersome quality-of-life issues and compared approaches for interpreting PRO scores.

Methods

This secondary data analysis included 130 patients with cancer (mean age, 57 years; 71% female) receiving outpatient palliative chemotherapy. Patients completed a PRO (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire [QLQ-C30]) at up to three consecutive visits and reported one or two of their most bothersome function and symptom issues from categories based on QLQ-C30 domains. We compared two approaches for interpreting PRO scores and identified which way better identified patients' most bothersome issues: worst scores in absolute terms or worst change from the previous time point.

Results

For patients reporting one bothersome issue, absolute scores identified it correctly 91% of the time for both function and symptoms versus change scores' accuracy of 40% for function and 26% for symptoms. For patients reporting two bothersome issues, absolute scores identified at least one correctly 98% of the time for both function and symptoms versus change scores' 63% for function and 62% for symptoms. Absolute scores identified both issues correctly 42% of the time for function and 66% of the time for symptoms versus change scores' performance of 23% for both function and symptoms.

Conclusion

Absolute scores identify patients' most bothersome quality-of-life issues better than change scores. These results support the use of PROs in clinical practice and suggest that clinicians may want to focus on the worst absolute scores when examining PRO score reports.