bluuebunny/crossref_metadata_2025_split huggingface dataset:
De-Repression of PDGFRβ Transcription Promotes Acquired Resistance to EGFR Tyrosine Kinase Inhibitors in Glioblastoma Patients
Authors: Akhavan David , Pourzia Alexandra L. , Nourian Alex A. , Williams Kevin J. , Nathanson David , Babic Ivan , Villa Genaro R. , Tanaka Kazuhiro , Nael Ali , Yang Huijun , Dang Julie , Vinters Harry V. , Yong William H. , Flagg Mitchell , Tamanoi Fuyuhiko , Sasayama Takashi , James C. David , Kornblum Harley I. , Cloughesy Tim F. , Cavenee Webster K. , Bensinger Steven J. , Mischel Paul S. 
Published: March 2013

Abstract
Acquired resistance to tyrosine kinase inhibitors (TKI) represents a major challenge for personalized cancer therapy. Multiple genetic mechanisms of acquired TKI resistance have been identified in several types of human cancer. However, the possibility that cancer cells may also evade treatment by co-opting physiologically regulated receptors has not been addressed. Here, we show the first example of this alternate mechanism in brain tumors by showing that EGF receptor (EGFR)-mutant glioblastomas (GBMs) evade EGFR TKIs by transcriptionally de-repressing platelet-derived growth factor receptor β (PDGFRβ). Mechanistic studies show that EGFRvIII signaling actively suppresses PDGFRβ transcription in an mTORC1- and extracellular signal–regulated kinase-dependent manner. Genetic or pharmacologic inhibition of oncogenic EGFR renders GBMs dependent on the consequently de-repressed PDGFRβ signaling for growth and survival. Importantly, combined inhibition of EGFR and PDGFRβ signaling potently suppresses tumor growth in vivo. These data identify a novel, nongenetic TKI resistance mechanism in brain tumors and provide compelling rationale for combination therapy.
Significance: These results provide the first clinical and biologic evidence for receptor tyrosine kinase (RTK) “switching” as a mechanism of resistance to EGFR inhibitors in GBM and provide a molecular explanation of how tumors can become “addicted” to a nonamplified, nonmutated, physiologically regulated RTK to evade targeted treatment. Cancer Discov; 3(5); 534–47. ©2013 AACR.
This article is highlighted in the In This Issue feature, p. 471
Repeat Coronary Revascularization After Coronary Artery Bypass Surgery in Older Adults
Authors: Fosbøl Emil L. , Zhao Yue , Shahian David M. , Grover Frederick L. , Edwards Fred H. , Peterson Eric D. 
Published: March 2013

Background—
A major advantage of coronary artery bypass graft surgery (CABG) relative to percutaneous coronary intervention is its durability, yet there is a paucity of information on rates and predictors of repeat coronary revascularization after CABG in the modern era.

Methods and Results—
We included patients ≥65 years from the Society of Thoracic Surgeons’ National Adult Cardiac Surgery Database who were undergoing first-time isolated CABG from 1991 to 2007 (n=723 134, median age 73 years). After linking to Medicare claims data, long-term outcomes of CABG (up to 18 years after surgery) were examined by use of cumulative incidence curves. Multivariable Cox proportional hazard analysis was used to identify factors associated with 1- and 5-year repeat revascularization trends and variability. We found that the overall 18-year survival rate was 20%. Cumulative incidences of any repeat revascularization (percutaneous coronary intervention or CABG, yet most often percutaneous coronary intervention) were 2%, 7%, 13%, and 16% at 1, 5, 10, and 18 years after surgery, respectively. The rates of repeat CABG procedures were quite low for all time points (0.1%, 0.6%, 1.3%, and 1.7%, respectively). Female sex, disease severity represented by a history of percutaneous coronary intervention, preoperative dialysis, and partial revascularization were strongly associated with a higher revascularization rate, whereas advanced age, left main disease, and smoking were associated with a lower rate. There was approximately a 2-fold variation in repeat revascularization rates across centers at 1 year (interquartile range 1.7–3.6%) and 5 years (interquartile range 6.7–12.0%).

Conclusions—
Repeat revascularization is performed infrequently among older patients who undergo CABG; however, these rates vary substantially by patient subgroups and among providers.
Risk Factors for Intracerebral Hemorrhage
Authors: Howard George , Cushman Mary , Howard Virginia J. , Kissela Brett M. , Kleindorfer Dawn O. , Moy Claudia S. , Switzer Jeffery , Woo Daniel 
Published: March 2013

Background and Purpose—
Risk factors for intracerebral hemorrhage (ICH) have been largely identified in case–control studies, with few longitudinal studies available.

Methods—
Predictors of incident ICH among 27 760 black and white participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study were assessed.

Results—

There were 62 incident ICH events during an average follow-up of 5.7 years. The increase in risk with age differed substantially between blacks and whites (
P
=0.006), with a 2.25-fold (95% confidence interval, 1.63–3.12) increase per decade in whites, but no age association with ICH risk in blacks (hazard ratio=1.09; 95% confidence interval, 0.70–1.68). We observed increased risk among men, those with higher systolic blood pressure, and warfarin users.

Conclusions—
The racial differences in the impact of age contributed to a risk of ICH that was >5 times higher for blacks than whites at age 45, but only about one third as great by age 85. Confirming findings from other studies, men participants with elevated systolic blood pressure and warfarin users were also at greater risk. The contributors to the racial differences in ICH risk require additional investigation.
Malignant Emboli on Transcranial Doppler During Carotid Stenting Predict Postprocedure Diffusion-Weighted Imaging Lesions
Authors: Almekhlafi Mohammed A. , Demchuk Andrew M. , Mishra Sachin , Bal Simerpreet , Menon Bijoy K. , Wiebe Samuel , Clement Fiona M. , Wong John H. , Hill Michael D. , Goyal Mayank 
Published: March 2013

Background and Purpose—
Carotid angioplasty and stenting (CAS) has a higher incidence of periprocedural stroke compared with endarterectomy. Identifying CAS steps with the highest likelihood of embolization may have important implications. We evaluated CAS safety by correlating the findings of procedural transcranial Doppler with postprocedure diffusion-weighted imaging (DWI) lesions.

Methods—
In this prospective study, transcranial Doppler monitoring was performed during CAS procedures, which were divided into 11 steps. Embolic signals on transcranial Doppler were counted and classified based on the relative energy index of microembolic signals into microemboli ≤1 or malignant macroemboli >1. Poststenting MRI was performed in all cases. A negative binomial regression model was used to evaluate the predictive value of transcranial Doppler emboli for new DWI lesions.

Results—

Thirty subjects were enrolled. Seven of 30 subjects (23.3%) were asymptomatic. The median embolic signal count was 212.5 (108 microemboli and 80 malignant macroemboli). Stent deployment phase showed the highest median embolic signals count at 58, followed by protection device deployment at 30 (
P
=0.0006). Twenty-four of 30 (80%) had new DWI lesions on post-CAS MRI. The median DWI count was 4 (interquartile range 7). Two of 30 (6.7%) had new or worsening clinical deficits post-CAS. For every malignant embolus, the expected count of DWI lesions increases by 1% ( 95% confidence interval, 0%–2%;
P
=0.032).

Conclusions—
We observed a high incidence of embolic signals during CAS procedure, especially, when devices were deployed. Most subjects developed new DWI lesions, but only 6.7% had deficits. Malignant macroemboli predicted new DWI lesions.
Exploration of a Group Model in Fieldwork Education
Authors: Farrow Susan , Gaiptman Barbara , Rudman Deborah 
Published: March 2013

Objective. Organizational changes, such as program management and managed care, and fluctuations in resources present challenges to the effective provision of fieldwork placements. This study compared an innovative group model with a traditional 1:1 supervision model to determine their effect on students and supervisors. Method: The two models were implemented at an urban clinical facility in several areas of practice over a 2 year period. Questionnaires were used to assess student skill development, student and supervising therapist satisfaction, and impact on supervising therapists' use of time. Focus groups were used to explore the advantages and disadvantages of each model. Results. There were few statistically significant differences in students' (n=26) and supervising therapists' (n=28) ratings when the two models were compared. The qualitative findings suggest that the advantages of one model often relate to the disadvantages of the other model. In addition, supervising therapists and students offered several suggestions for how to improve implementation of the group model. Conclusion: When the results of the study are compared to the objectives established for the group model, it appears that many of the objectives outlined for the model were partially achieved. Several issues, such as the student-supervisor relationship and the evaluation process, need to be addressed with participants to ensure successful implementation of the group model.
Meaning of Occupational Engagement in Life-Threatening Illness: A Qualitative Pilot Project
Authors: Vrkljan Brenda , Miller-Polgar Janice 
Published: March 2013

INTRODUCTION: The onset of a personal crisis combined with the resultant disruption in occupational routines may challenge a person's identity as a capable and healthy individual. However, it remains unclear how individuals regain a sense of health and well-being in the period following a personal crisis. RESEARCH OBJECTIVE: To explore occupational engagement and its meaning to individuals following a life-threatening diagnosis. METHOD: Semi-structured interviews were conducted with three women diagnosed with breast cancer. The data were analyzed using a constant-comparative approach to identify common themes. RESULTS: The primary theme that emerged was “Doing = Living.” This theme and the underlying themes illustrated the connection between meaningful occupational engagement and one's self-perception as capable and healthy. These findings suggest that occupational engagement may provide the medium through which ‘deconstructive’ or ‘reconstructive’ messages concerning the self are relayed between persons and their environment. IMPLICATIONS: In a period of personal crisis, such as a life-threatening diagnosis, individuals may turn to those occupations that are meaningful to regain a sense of control and normalcy in their lives.
LE ROLE DE L'ERGOTHERAPEUTE EN MILIEU SCOLAIRE
Authors: Boucher Monique G. , Menard Therese 
Published: March 2013

Dans le futur, la reconnaissance du titre de professionnels de la santé, pour les membres de notre profession, ne sera possible qu'au prix d'une formation scientifique plus poussée et d'une compétence accrue, dans ce qui fait la spécificité de notre approche. L'amateurisme devra donc céder la place à la compétence professionnelle et notre philosophie devra s'adapter aux valeurs et besoins changeants d'une société en évolution. L'article présente à titre d'exemple l'orientation et l'organisation globale du cours donné à L'Université “Western” d'Ontario et l'auteur termine par une série de suggestions, susceptibles de pourvoir au développement actuel de notre profession. This is the report of a study carried out at the Ecole Victor Doré, Montreal. The purpose of the study was to further understand the role the occupational therapist can play in a school setting. One of the main areas studied was that of perception and how perceptual deficits affect a child's ability to learn when he reaches the stage of learning through reading and writing. Further study was done in the area of independence in self-care activities, the role of the O.T. on the multi-disciplinary team and the problems faced by the handicapped child when integrated into a regular school.
Poetry — A Therapeutic Tool
Authors: Zink Tannis M. 
Published: March 2013

Poetry has been successfully used as a group technique for many years yielding material which can be interpreted using a similar system as used with any other projective material. Four stages of poetic development are described as: “Pre-Poetry Stage” “First ‘Outpouring’ Stage” “Second ‘Narrative’ Stage” “Third ‘Mature’ Stage” which, in turn, relate to the mental health of the individual producing poetry. A practical description of a poetry group is included along with step-by-step particulars of a method of organization.
Comparative Analysis of Occupational Therapy Prevocational Assessments and Industrial Vocational Assessments: A Pilot Study
Authors: Robinson Karen L. , Gill Thelma , Bull Shelley B. , Spaulding Sandi J. 
Published: March 2013

The present investigation was undertaken for the purpose of looking at the correlation between industrial pre-employment assessments and the prevocational assessments used by clinical occupational therapists. This pilot study involved the surveying of a sample of different-sized industries in the London, Ontario area. A similar survey of practising occupational therapists was also done in London. The authors were interested in the prevalence of test usage, the average number of tests used by industry and therapists, and specifically, the types of tests used by both groups. Conclusions centre around two ideas: (a) If occupational therapy prevocational assessment usage is concerned primarily with ascertaining patient skill level in a work approach for patient/therapist feedback purposes, then perhaps there should be no concern with correlating these activities with industry in the London area; (b) If communication between therapists and industry in the London area is to be enhanced for the purposes of providing possible client placement and more meaningful information for vocational rehabilitation personnel, a common ground for discussion and negotiation could be gained by using the same or similar tests. This may encourage a greater future success rate in placing prevocationally assessed clients in job situations in the London area. A larger nation-wide sample of industry and occupational therapy departments may further elucidate this issue in order to keep occupational therapists abreast of the changing needs of Canadian industry.
Prevocational Exploration and Vocational Rehabilitation of the Psychiatric Client
Authors: Stein Franklin 
Published: March 2013

The primary objective of this paper is to survey current trends in the United States in the use of vocational rehabilitation services for the psychiatric client in relation to occupational therapy. In assessing the techniques and services that can be employed by occupational therapists working in psychiatric rehabilitation centers, nine vocational rehabilitation prototypes have been identified, i.e., evaluation of skills and aptitudes, occupational information groups, individual counseling, vocational training, pre-employment group counseling, transitional volunteer work, sheltered work, temporary tryout work, and special placement. Based on a number of descriptive clinical studies, it can be concluded that vocational rehabilitation serves as a key factor in a comprehensive psychiatric treatment program located in the community. In general, work provides the psychiatric client with opportunities to be in the mainstream of life and to attain the psychological satisfactions that are derived from being employed.
Community Care for the Chronic Mentally Ill
Authors: Woodside Harriet 
Published: March 2013

The movement of chronic mentally ill patients from large mental hospitals into the community, seeks to liberate institutionalized clients and substitute a more humane environment. This article reviews the types of chronic mental patients now living in the community. The differences between a maintenance and a rehabilitation model for treating the chronic mental patient living in the community are discussed. Special treatment programs for the young adult chronic client are also considered. Three questions specific to occupational therapists working with chronic mentally ill patients in the community are then explored. These are: A. How can we increase the visibility of occupational therapy in community mental health?; B. Should occupational therapists be involved in programs which have a maintenance, rather than a rehabilitation focus?: and C. What has the occupational therapist to offer the young adult chronic client?
Activities of Daily Living, Cognitive Impairment and Social Function in Community Residents with Alzheimer Disease
Authors: Carswell Anne , Eastwood Robin 
Published: March 2013

One hundred and one patients with Alzheimer disease who were residing in the community were surveyed twice, in a six-month longitudinal study. A strong linear relationship was found between function, as measured by activities of daily living and cognitive impairment and between activities of daily living and social function. At the first interview the proportion of variance in activities of daily living explained by cognitive impairment and social function, controlling for age, estimated duration of the disease and marital status was 65%. After six months the proportion had increased to 67%. The proportion of social function accounted for by activities of daily living was 30% at the initial interview; the proportion increased to 43% after six months. Patients lose the ability to perform instrumental activities of daily living before they lose the ability to perform self-care activities. The pattern of deterioration in activities of daily living is hierarchical. The results of the study have implications for assessment and for intervention programmes. For those patients who have a diagnosis of Alzheimer disease, measures of activities of daily living are more useful for helping caregivers and for planning intervention programmes than measures of cognitive impairment.
Client-Centred Care Means that I am a Valued Human Being
Authors: Corring Deborah , Cook Joanne 
Published: March 2013

Canadian occupational therapists have increasingly adopted a client-centred approach to practice. Interpretation of what “client-centred” means has been diverse and varied. Professionals have written about the characteristics of this approach to care but no reported studies could be found that examined the client's perspective. The omission of the client perspective is puzzling when partnership, client involvement in decision making, and client empowerment are thought to be fundamental elements of this approach to practice. A qualitative research approach, using focus groups was employed to explore the opinions and perspectives of individuals with experience of mental illness and the mental health service delivery system. Seventeen individuals participated in three focus groups to discuss the meaning of a client-centred approach to practice. Participants assessed the inadequacies of past and present practices and recommended needed changes. Their central message was the need for individuals with mental illness to be viewed as valuable human beings by service providers and by society.
Panel 1: Epidemiology, Natural History, and Risk Factors
Authors: Hoffman Howard J. , Daly Kathleen A. , Bainbridge Kathleen E. , Casselbrant Margaretha L. , Homøe Preben , Kvestad Ellen , Kvaerner Kari Jorunn , Vernacchio Louis 
Published: March 2013

BackgroundThe First International Symposium on Recent Advances in Otitis Media (OM) with Effusion was held in Columbus, Ohio, in 1975. The symposium has been organized in the United States every 4 years since, followed by a research conference to (a) assess major research accomplishments, (b) identify important research questions and opportunities, (c) develop consensus on definitions and terminology, and (d) establish priorities with short‐ and long‐term research goals. One of the principal areas reviewed quadrennially is Epidemiology, Natural History, and Risk Factors.ObjectiveTo provide a review of recent literature on the epidemiology, natural history, and risk factors for OM.Data Sources and Review MethodsA search of OM articles in English published July 2007 to June 2011 was conducted using PubMed and related databases. Those with findings judged of importance for epidemiology, public health, and/or statistical methods were reviewed.ResultsThe literature has continued to expand, increasing understanding of the worldwide burden of OM in childhood, complications from treatment failures, and comorbidities. Novel risk factors, including genetic factors, have been examined for OM susceptibility. Population‐based studies in Canada, the United States, and other countries confirmed reductions in OM prevalence. Although most studies concentrated on acute OM (AOM) or OM with effusion (OME), a few examined severe chronic suppurative OM (CSOM), a major public health problem in developing countries and for certain indigenous populations around the world.Conclusions and Implications for PracticeRecent publications have reinforced earlier epidemiological findings, while extending our knowledge in human population groups with high burden of OM.
Panel 8: Complications and Sequelae
Authors: Jung Timothy T. K. , Alper Cuneyt M. , Hellstrom Sten O. , Hunter Lisa L. , Casselbrant Margaretha L. , Groth Anita , Kemaloglu Yusuf K. , Kim Sang Gyoon , Lim David , Nittrouer Susan , Park Kee Hyun , Sabo Diane , Spratley Jorge 
Published: March 2013

Background and ObjectivesAlthough serious complications of otitis media (OM) such as brain abscess are rare, sequelae of OM such as tympanic membrane perforation and atelectatic tympanic membrane are quite common. Inner ear sequelae can cause hearing loss and speech and language problems. The objectives of this article are to provide a state‐of‐the‐art review on recent articles on complications and sequelae of OM in different anatomic locations, from the tympanic membrane to intracranial sites, as well as hearing loss and speech and language development.Data SourcesPrimarily PubMed supplemented by Ovid MEDLINE and the Cochrane Database.Review MethodsAll types of articles related to OM complications and sequelae published in English between January 2007 and June 2011 were identified. A total of 127 relevant quality articles are summarized and included in this report.ResultsKey findings are summarized based on the following major anatomic locations and categories: tympanic membrane; cholesteatoma; ossicular problems; mucosal sequelae; inner ear sequelae; speech and language development; extracranial areas, including mastoiditis and facial nerve paralysis; intracranial complications; and future research goals. New information and insights were gained to prevent complications and sequelae.Conclusion and Implications for PracticeOver the past 4 years, progress has been made in advancing the knowledge on the complications and sequelae of OM, which can be used to prevent and treat them effectively. Areas of potential future research have been identified and outlined.