bluuebunny/crossref_metadata_2025_split huggingface dataset:
Including Adults With Intellectual Disabilities in Research: Scientists' Perceptions of Risks and Protections
Authors: McDonald Katherine E. , Kidney Colleen A. , Nelms Sandra L. , Parker Michael R. , Kimmel Ali , Keys Christopher B. 
Published: December 2009

AbstractSocial and cognitive characteristics of adults with intellectual disabilities (ID) place them at risk for inappropriate inclusion in or exclusion from research participation. As we grapple with how to include adults with ID in research in order to secure their right to contribute to scientific advancements and be positioned to derive benefit from ensuing knowledge, it is critical to consider scientific gatekeepers' perspectives on risks of and protections for including adults with ID in research. We surveyed 199 Institutional Review Board members and intellectual disability researchers in the United States to identify their perceptions of specific risks and necessary protections in (hypothetical) research studies. The research studies varied as to whether they included adults with ID in the research sample and the level of harm to which research participants were exposed. Results suggest that identification of psychological, social, and legal risks and necessary protections varied by the disability status of the sample, the level of risk, and the role of the person reviewing the study. For example, participants identified more psychological, information control, legal, and social risks in higher harm research studies. Participants reported a need for more protections in high‐harm studies as well as studies that included adults with ID. In some instances the nature of identified risks and protections and respondents' characterization of these risks and necessary protections suggested concerns related specifically to adults with ID. Implications for practice, policy, and future research related to access to research participation are discussed.
Eight Years of Specialist Training of Dutch Intellectual Disability Physicians: Results of Scientific Research Education
Authors: Evenhuis Heleen M. , Penning Corine 
Published: December 2009

AbstractTraining in scientific research methods and skills is a vital part of Dutch specialist training in intellectual disability medicine. The authors evaluated results of such training at one Dutch university medical facility that had an obligatory research program involving projects conducted by the physicians‐in‐training (topics, teamwork, acquired competencies, and products). Since 2000, 28 research projects were started, and 24 of them were completed by teams made up of two to five trainees. Project topics included syndrome‐related comorbidity (n = 8), lifestyle (n = 2), specific medical conditions (n = 5), diagnostic methods (n = 5), and care by intellectual disability physicians (n = 8). Sixteen of the study designs were cross‐section observational, five were retrospective file reviews, one dealt with instrument development, three were qualitative, and three were literature studies. Structured exit evaluation interviews with 57 trainees (20 teams) showed that teamwork was appreciated positively by 17 of the teams, negatively by one, and mixed by two teams. While skills in literature search were reported as competencies present prior to the specialist training, additional basic scientific competencies were reported as acquired or improved by over 50% of trainees (including translating clinical into research questions, literature appraisal, protocol writing, data collection in the field, data entry, critical–analytical competency, and dealing with feedback and criticism). Trainee end products include 16 written reports, three journal articles in Dutch‐language publications, eight articles in international journals, and 14 international congress presentations/publications.
Defining “Sexualized Challenging Behavior” in Adults With Intellectual Disabilities
Authors: Lockhart Karen , Guerin Suzanne , Shanahan Sean , Coyle Kevin 
Published: December 2009

AbstractInappropriate sexual behaviors are a subset of challenging behaviors that limit the community integration of individuals with intellectual disabilities. Despite the stigmatizing effect of problematic sexual behavior, research efforts in this area have been limited and often used narrow prospective definitions. As such, research has been limited to a focus on “sexual offending” and “abuse,” terms which are often criticized in their applicability to people with intellectual disabilities given their connotations of criminal intent or insight. The authors propose adopting the term “sexualized challenging behavior” and define it by using empirical methods. Using a qualitative methodology, they examined a six‐month sample of service‐based documentation reporting sexual behaviors that were problematic. They also conducted semi‐structured interviews with a staff‐based sample and explored their views in relation to sexual behavior. Common themes emerged across both documentation and staff interviews regarding the nature and characteristics of such behaviors. Their proposed definition encompasses a continuum of self‐ and other‐directed behaviors related to touch, exposure, and communication, which they view as distinct from sexual offending. The findings further suggest that sexualized challenging behaviors have distinct characteristics that differentiate them from nonsexualized challenging behaviors. The authors conclude that sexualized challenging behaviors can be defined as a distinct class of behaviors that require further study among a broader cohort of adults with intellectual disabilities.
Strength of Habitat and Landscape Metrics in Predicting Golden‐Headed Lion Tamarin Presence or Absence in Forest Patches in Southern Bahia, Brazil
Authors: Raboy Becky E. , Neves Leonardo G. , Zeigler Sara , Saraiva Nicholas A. , Cardoso Nayara , dos Santos Gabriel Rodrigues , Ballou Jonathan D. , Leimgruber Peter 
Published: December 2009

ABSTRACTWe investigated the effects of forest fragmentation on golden‐headed lion tamarins (Leontopithecus chrysomelas) by qualitatively and quantitatively characterizing the landscape throughout the species range, conducting surveys, and exploring predictive models of presence and absence. We identified 784 forest patches that varied in size, shape, core area, habitat composition, elevation, and distance to neighboring patches and towns. We conducted 284 interviews with local residents and 133 playback experiments in 98 patches. Results indicated a reduction in the western portions of the former species range. We tested whether L. chrysomelas presence or absence was related to the aforementioned fragmentation indices using Monte Carlo logistic regression techniques. The analysis yielded a majority of iterations with a one‐term final model of which Core Area Index (percent of total area that is core) was the only significant type. Model concordance ranged between 65 and 90 percent. Area was highlighted for its potential predictive ability. Although final models for area lacked significance, their failure to reach significance was marginal and we discuss potential confounding factors weakening the term's predictive ability. We conclude that lower Core Area Index scores are useful indicators of forest patches at risk for not supporting L. chrysomelas. Taken together, our analyses of the landscape, survey results, and logistic regression modeling indicated that the L. chrysomelas metapopulation is facing substantial threat. The limited vagility of lion tamarins in nonforest matrix may lead to increasingly smaller and inbred populations subject to significant impact from edge effects and small population size. Local extinction is imminent in many forest patches in the L. chrysomelas range.
Probing the corticospinal link between the motor cortex and motoneurones: some neglected aspects of human motor cortical function
Authors: Petersen N. C. , Butler J. E , Taylor J. L , Gandevia S. C. 
Published: December 2009

AbstractThis review considers the operation of the corticospinal system in primates. There is a relatively widespread cortical area containing corticospinal outputs to a single muscle and thus a motoneurone pool receives corticospinal input from a wide region of the cortex. In addition, corticospinal cells themselves have divergent intraspinal branches which innervate more than one motoneuronal pool but the synergistic couplings involving the many hand muscles are likely to be more diverse than can be accommodated simply by fixed patterns of corticospinal divergence. Many studies using transcranial magnetic stimulation of the human motor cortex have highlighted the capacity of the cortex to modify its apparent excitability in response to altered afferent inputs, training and various pathologies. Studies using cortical stimulation at ‘very low’ intensities which elicit only short‐latency suppression of the discharge of motor units have revealed that the rapidly conducting corticospinal axons (stimulated at higher intensities) drive motoneurones in normal voluntary contractions. There are also major non‐linearities generated at a spinal level in the relation between corticospinal output and the output from the motoneurone pool. For example, recent studies have revealed that the efficacy of the human corticospinal connection with motoneurones undergoes activity‐dependent changes which influence the size of voluntary contractions. Hence, corticospinal drives must be sculpted continuously to compensate for the changing functional efficacy of the descending systems which activate the motoneurones. This highlights the need for proprioceptive monitoring of movements to ensure their accurate execution.
Molecular analyses of Xenopus laevis Mesp‐related genes
Authors: HITACHI Keisuke , KONDOW Akiko , DANNO Hiroki , NISHIMURA Yusuke , OKABAYASHI Koji , ASASHIMA Makoto 
Published: December 2009

AbstractDuring vertebrate somitogenesis, somites bud off from the anterior end of the presomitic mesoderm (PSM). Mesodermal posterior (Mesp)‐related genes play essential roles in somitogenesis, particularly in the definition of the somite boundary position. Among vertebrates, two types of Mesp‐related genes have been identified: Mesp1 and Mesp2 in the mouse; Meso‐1 and Meso‐2 in the chicken; Xl‐mespa and Xl‐mespb (also known as Thylacine1) in the African clawed frog (Xenopus laevis); and mesp‐a and mesp‐b in the zebrafish. However, the functional differences between two Mesp‐related genes remain unknown. In the present study, we carried out comparative analyses of the Xl‐mespa and Xl‐mespb genes. The amino acid sequences of the Xl‐mespa and Xl‐mespb proteins showed a high level of similarity. The expression of Xl‐mespa started broadly in the ventrolateral mesoderm and gradually shifted to a striped pattern of expression. In contrast, Xl‐mespb showed a striped pattern of expression from the start. These expression profiles completely overlapped at the PSM during somitogenesis. To investigate the functional differences between Xl‐mespa and Xl‐mespb in terms of target gene regulation, we carried out a luciferase assay using the murine Lunatic fringe (L‐fng) promoter. Transcription of the L‐fng promoter was activated more strongly by Xl‐mespb than by Xl‐mespa. This same pattern was observed for the murine Mesp‐related proteins. These results suggest that the functional differences between the two types of Mesp‐related genes are evolutionally conserved in vertebrates.
Canada's inter‐agency wild bird influenza survey
Authors: PARMLEY Jane , LAIR Stéphane , LEIGHTON Frederick A. 
Published: December 2009

AbstractCanada's Inter‐agency Wild Bird Influenza Survey, which started in 2005, and is a collaborative effort among federal, provincial and territorial government agencies as well as non‐governmental organizations and academic institutions, has two components: (i) a seasonal survey of live wild waterfowl species from selected geographic regions across Canada (to expand our understanding of the avian influenza viruses circulating in wild bird populations); and (ii) an ongoing survey of birds found dead that are submitted to a regional diagnostic laboratory (to enhance detection of highly pathogenic avian influenza strains). Combined swabs from the cloaca and oropharynx collected from each bird are screened using a real‐time reverse transcriptase‐polymerase chain reaction (RRT‐PCR) that targets a unique segment of the influenza A M1 gene. If the M1 result is positive or inconclusive, RRT‐PCR for gene segments of the H5 and H7 hemagglutinin subtypes are performed. All samples that are RRT‐PCR positive for H5 or H7 are sent immediately for test confirmation and further characterization. All field and laboratory data are entered into a database developed and maintained by the Canadian Cooperative Wildlife Health Centre. Since the survey commenced in 2005, on average, 30% of all live ducks sampled, 5% of other species of live birds and 3% of birds found dead have tested positive for avian influenza, all of North American lineage and of low pathogenicity.
Integration of subclassification strategies in randomised controlled clinical trials evaluating manual therapy treatment and exercise therapy for non-specific chronic low back pain: a systematic review
Authors: Fersum K V , Dankaerts W , O'Sullivan P B , Maes J , Skouen J S , Bjordal J M , Kvåle A 
Published: December 2009

BackgroundThere is lack of evidence for specific treatment interventions for patients with non-specific chronic low back pain (NSCLBP) despite the substantial amount of randomised controlled clinical trials evaluating treatment outcome for this disorder.HypothesisIt has been hypothesised that this vacuum of evidence is caused by the lack of subclassification of the heterogeneous population of patients with chronic low back pain for outcome research.Study designA systematic review.MethodsA systematic review with a meta-analysis was undertaken to determine the integration of subclassification strategies with matched interventions in randomised controlled clinical trials evaluating manual therapy treatment and exercise therapy for NSCLBP. A structured search for relevant studies in Embase, Cinahl, Medline, PEDro and the Cochrane Trials Register database, followed by hand searching all relevant studies in English up to December 2008.ResultsOnly 5 of 68 studies (7.4%) subclassified patients beyond applying general inclusion and exclusion criteria. In the few studies where classification and matched interventions have been used, our meta-analysis showed a statistical difference in favour of the classification-based intervention for reductions in pain (p=0.004) and disability (p=0.0005), both for short-term and long-term reduction in pain (p=0.001). Effect sizes ranged from moderate (0.43) for short term to minimal (0.14) for long term.ConclusionA better integration of subclassification strategies in NSCLBP outcome research is needed. We propose the development of explicit recommendations for the use of subclassification strategies and evaluation of targeted interventions in future research evaluating NSCLBP.
MicroRNA-145 Suppresses Cell Invasion and Metastasis by Directly Targeting Mucin 1
Authors: Sachdeva Mohit , Mo Yin-Yuan 
Published: December 2009

Abstract
MicroRNAs are important gene regulators that could play a profound role in tumorigenesis. Our previous studies indicate that miR-145 is a tumor suppressor capable of inhibiting tumor cell growth both in vitro and in vivo. In this study, we show that miR-145 exerts its function in a cell-specific manner. Although miR-145 inhibits cell growth in MCF-7 and HCT-116 cells, it has no significant effect on cell growth in metastatic breast cancer cell lines. However, miR-145 significantly suppresses cell invasion in these cells; in contrast, the antisense oligo against miR-145 increases cell invasion. miR-145 is also able to suppress lung metastasis in an experimental metastasis animal model. This miR-145–mediated suppression of cell invasion is in part due to the silencing of the metastasis gene mucin 1 (MUC1). Using luciferase reporters carrying the 3′-untranslated region of MUC1 combined with Western blot and immunofluorescence staining, we identify MUC1 as a direct target of miR-145. Moreover, ectopic expression of MUC1 enhances cell invasion, which can be blocked by miR-145. Of interest, suppression of MUC1 by miR-145 causes a reduction of β-catenin as well as the oncogenic cadherin 11. Finally, suppression of MUC1 by RNAi mimics the miR-145 action in suppression of invasion, which is associated with downregulation of β-catenin and cadherin 11. Taken together, these results suggest that as a tumor suppressor, miR-145 inhibits not only tumor growth but also cell invasion and metastasis. Cancer Res; 70(1); 378–87
Biomarkers Predictp53Gene Therapy Efficacy in Recurrent Squamous Cell Carcinoma of the Head and Neck
Authors: Nemunaitis John , Clayman Gary , Agarwala Sanjiv S. , Hrushesky William , Wells James R. , Moore Charles , Hamm John , Yoo George , Baselga Jose , Murphy Barbara A. , Menander Kerstin A. , Licato Laura L. , Chada Sunil , Gibbons Robert D. , Olivier Magali , Hainaut Pierre , Roth Jack A. , Sobol Robert E. , Goodwin W. Jarrard 
Published: December 2009

AbstractPurpose: Most recurrent squamous cell carcinomas of the head and neck have a dysfunctional p53 tumor suppressor pathway contributing to treatment resistance. We hypothesized that tumor p53 biomarkers may predict the efficacy of normal p53 delivered by gene therapy in these patients.Experimental Design: Tumor p53 biomarkers were evaluated in 116 patients, including 29 treated with methotrexate in a phase III randomized controlled trial. Profiles favorable for p53 gene therapy efficacy were hypothesized to have either normal p53 gene sequences or low-level p53 protein expression, whereas unfavorable p53 inhibitor profiles were predicted to have high-level expression of mutated p53 that can inhibit normal p53 protein function.Results: A statistically significant increase in tumor responses was observed for patients with favorable p53 efficacy profiles compared with those with unfavorable p53 inhibitor profiles [phase I/II trials: favorable (34 of 46, 74%) versus unfavorable (1 of 5, 20%), P = 0.0290; phase III trial: favorable (17 of 24, 71%) versus unfavorable (2 of 11, 18%), P = 0.0088]. In the phase III trial, there was statistically significant increased time to progression (TTP) and survival following p53 gene therapy in patients with favorable p53 profiles compared with unfavorable p53 inhibitor profiles (median TTP, 2.7 months versus 1.4 months, P = 0.0121; median survival, 7.2 months versus 2.7 months, P &lt; 0.0001). In contrast, the biomarker profiles predictive of p53 gene therapy efficacy did not predict methotrexate response, TTP, or survival outcomes.Conclusions: These results indicate that tumor p53 biomarker profiles may predict p53 gene therapy efficacy in recurrent squamous cell carcinoma of the head and neck. (Clin Cancer Res 2009;15(24):7719–25)
Metastasis-Associated Gene Expression Changes Predict Poor Outcomes in Patients with Dukes Stage B and C Colorectal Cancer
Authors: Jorissen Robert N. , Gibbs Peter , Christie Michael , Prakash Saurabh , Lipton Lara , Desai Jayesh , Kerr David , Aaltonen Lauri A. , Arango Diego , Kruhøffer Mogens , Ørntoft Torben F. , Andersen Claus Lindbjerg , Gruidl Mike , Kamath Vidya P. , Eschrich Steven , Yeatman Timothy J. , Sieber Oliver M. 
Published: December 2009

AbstractPurpose: Colorectal cancer prognosis is currently predicted from pathologic staging, providing limited discrimination for Dukes stage B and C disease. Additional markers for outcome are required to help guide therapy selection for individual patients.Experimental Design: A multisite single-platform microarray study was done on 553 colorectal cancers. Gene expression changes were identified between stage A and D tumors (three training sets) and assessed as a prognosis signature in stage B and C tumors (independent test and external validation sets).Results: One hundred twenty-eight genes showed reproducible expression changes between three sets of stage A and D cancers. Using consistent genes, stage B and C cancers clustered into two groups resembling early-stage and metastatic tumors. A Prediction Analysis of Microarray algorithm was developed to classify individual intermediate-stage cancers into stage A–like/good prognosis or stage D–like/poor prognosis types. For stage B patients, the treatment adjusted hazard ratio for 6-year recurrence in individuals with stage D–like cancers was 10.3 (95% confidence interval, 1.3-80.0; P = 0.011). For stage C patients, the adjusted hazard ratio was 2.9 (95% confidence interval, 1.1-7.6; P = 0.016). Similar results were obtained for an external set of stage B and C patients. The prognosis signature was enriched for downregulated immune response genes and upregulated cell signaling and extracellular matrix genes. Accordingly, sparse tumor infiltration with mononuclear chronic inflammatory cells was associated with poor outcome in independent patients.Conclusions: Metastasis-associated gene expression changes can be used to refine traditional outcome prediction, providing a rational approach for tailoring treatments to subsets of patients. (Clin Cancer Res 2009;15(24):7642–51)
miR-195 and miR-483-5p Identified as Predictors of Poor Prognosis in Adrenocortical Cancer
Authors: Soon Patsy Siok Hwa , Tacon Lyndal J. , Gill Anthony J. , Bambach Christopher P. , Sywak Mark S. , Campbell Peter R. , Yeh Michael W. , Wong Steven G. , Clifton-Bligh Roderick J. , Robinson Bruce G. , Sidhu Stan B. 
Published: December 2009

Abstract
Purpose: Adrenocortical adenomas are common, whereas adrenocortical carcinomas are rare. Discriminating between benign and malignant adrenocortical tumors using conventional histology can be difficult. In addition, adrenocortical carcinomas generally have poor prognosis and limited treatment options. MicroRNAs are short noncoding RNAs that are involved in regulation of gene transcription.
Experimental Design: To identify microRNAs involved in the pathogenesis of adrenocortical tumors, expression profiling of microRNAs was done on a cohort of 22 adrenocortical carcinomas, 27 adrenocortical adenomas, and 6 normal adrenal cortices.
Results: Twenty-three microRNAs were found to be significantly differentially expressed between adrenocortical carcinomas and adrenocortical adenomas. miR-335 and miR-195 were significantly downregulated in adrenocortical carcinomas compared with adrenocortical adenomas. This result was further validated in an external cohort of six adrenocortical carcinomas and four adrenocortical adenomas. Using Kaplan-Meier analysis, downregulation of miR-195 and upregulation of miR-483-5p in adrenocortical carcinomas were significantly associated with poorer disease-specific survival.
Conclusions: These findings indicate that deregulation of microRNAs is a recurring event in human adrenocortical carcinomas and that aberrant expression of miR-195 and miR-483-5p identifies a subset of poorer prognosis adrenocortical carcinomas. (Clin Cancer Res 2009;15(24):7684–92)