709 research outputs found
The Quandary of Serving Multiple Masters: An Institutional Exploratory Analysis of Publishing in Business Law
Notwithstanding published articles on the nature and quality of research and scholarship in practically every other business discipline, to date there has been little systematic evaluation of relevant journals in the business law discipline. This deficiency is due, in part, to the fact that business law may still be described as a developing discipline. Thus, the focus of this article is on delineating the nature of research and scholarship within the business law discipline. Specifically, the publishing practices of business law faculty from academic institutions that were members of the Association to Advance Collegiate Schools of Business (AACSB International), the premier international accrediting body for schools of business, were examined. The comparative perspective developed in this study provides a wide-ranging view of factors related to both the qualitative and quantitative aspects of research and scholarship among business law scholars
Novel functional view of the crocidolite asbestos-treated A549 human lung epithelial transcriptome reveals an intricate network of pathways with opposing functions
<p>Abstract</p> <p>Background</p> <p>Although exposure to asbestos is now regulated, patients continue to be diagnosed with mesothelioma, asbestosis, fibrosis and lung carcinoma because of the long latent period between exposure and clinical disease. Asbestosis is observed in approximately 200,000 patients annually and asbestos-related deaths are estimated at 4,000 annually<abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. Although advances have been made using single gene/gene product or pathway studies, the complexity of the response to asbestos and the many unanswered questions suggested the need for a systems biology approach. The objective of this study was to generate a comprehensive view of the transcriptional changes induced by crocidolite asbestos in A549 human lung epithelial cells.</p> <p>Results</p> <p>A statistically robust, comprehensive data set documenting the crocidolite-induced changes in the A549 transcriptome was collected. A systems biology approach involving global observations from gene ontological analyses coupled with functional network analyses was used to explore the effects of crocidolite in the context of known molecular interactions. The analyses uniquely document a transcriptome with function-based networks in cell death, cancer, cell cycle, cellular growth, proliferation, and gene expression. These functional modules show signs of a complex interplay between signaling pathways consisting of both novel and previously described asbestos-related genes/gene products. These networks allowed for the identification of novel, putative crocidolite-related genes, leading to several new hypotheses regarding genes that are important for the asbestos response. The global analysis revealed a transcriptome that bears signatures of both apoptosis/cell death and cell survival/proliferation.</p> <p>Conclusion</p> <p>Our analyses demonstrate the power of combining a statistically robust, comprehensive dataset and a functional network genomics approach to 1) identify and explore relationships between genes of known importance 2) identify novel candidate genes, and 3) observe the complex interplay between genes/gene products that function in seemingly different processes. This study represents the first function-based global approach toward understanding the response of human lung epithelial cells to the carcinogen crocidolite. Importantly, our investigation paints a much broader landscape for the crocidolite response than was previously appreciated and reveals novel paths to study. Our graphical representations of the function-based global network will be a valuable resource to model new research findings.</p
Computerized Tailored Interventions to Enhance Prevention and Screening for Hepatitis C Virus Among People Who Inject Drugs: Protocol for a Randomized Pilot Study.
BACKGROUND: Hepatitis C virus (HCV) infection is a growing problem among people who inject drugs. Strategies to reduce disease transmission (eg, syringe exchange programs) and facilitate HCV screening and linkage are available but are under-utilized in many communities affected by injection drug use. Novel approaches to increasing the use of these strategies are needed.
OBJECTIVE: The goals of this project are to (1) develop and pilot test a computerized tailored intervention for increasing HCV screening and decreasing risky drug use behavior among people who inject drugs and (2) determine the feasibility of disseminating such an intervention using peer-based referrals in the setting of a community-based syringe exchange program.
METHODS: This 2-arm, randomized pilot study is being conducted in a large-volume, multisite syringe exchange program in southern Wisconsin. A social network-based strategy was used to recruit a total of 235 adults who reported past-month injection of opioids, cocaine, or methamphetamine. Network recruiters were identified among clients requesting services from the syringe exchange program and were enlisted to refer eligible peers to the study. All participants completed a computer-adapted questionnaire eliciting information about risk behaviors and their knowledge, attitudes, and prior experiences related to HCV screening. Subjects were then randomly assigned to receive usual care, consisting of standard counseling by syringe exchange staff, or the Hep-Net intervention, which provides algorithm-based, real-time tailored feedback and recommendations for behavior change in the style of motivational interviewing. Changes in drug use behaviors and attitudes will be assessed during a second session between 90 and 180 days after the baseline visit. Frequency of repeat HCV testing and HCV incidence will be assessed through a database search 1 year after study completion.
RESULTS: Recruitment for this study was completed in April 2015. Follow-up of enrolled participants is expected to continue until March 2016. Network recruiters were enrolled who referred a total of 195 eligible peers (overall N=235). At baseline, the median age was 34 years; 41.3% (97/235) were non-white; and 86.4% (203/235) reported predominantly injecting heroin. Most participants (161/234, 68.8%) reported sharing injection equipment in the past and of these, 30.4% (49/161) had never been tested for HCV.
CONCLUSIONS: This study will provide preliminary evidence to determine whether incorporating computerized behavioral interventions into existing prevention services at syringe exchange programs can lead to adoption of healthier behaviors.
TRIAL REGISTRATION: ClinicalTrials.gov NCT02474043; https://clinicaltrials.gov/ct2/show/NCT02474043 (Archived by WebCite at http://www.webcitation.org/6dbjUQG7J)
The role of rigidity in adaptive and maladaptive families assessed by FACES IV: the points of view of adolescents
Previous studies using Olson’s Circumplex Model and FACES IV, the self-report assessing family functioning, did not clarify the role of rigidity, a dimension of this model. Rigidity emerged as ambiguous: it was considered either as a functional or as a dysfunctional dimension. Building upon the results of previous studies, we provided a contribution intended to disambiguate the role of rigidity considering adolescents’ perceptions and using a non-a priori classification analysis. 320 Italian adolescents (13–21 years) participated in this study and responded to a questionnaire containing scales of the study variables. A latent class analysis was performed to identify the association of rigidity with the other dimensions of Olson’s model and with indicators of adaptive family functioning in adolescence: parental monitoring and family satisfaction. We found six clusters corresponding to family typologies and having different levels of functioning. Rigidity emerged as adaptive in the typologies named rigidly balanced and flexibly oscillating; it was associated with positive dimensions of family functioning, i.e. flexibility, cohesion, parental monitoring, and high levels of family satisfaction. Differently, when rigidity was associated with disengagement, low cohesion and flexibility, and lack of parental supervision, emerged as maladaptive. This was the case of two typologies: the rigidly disengaged and the chaotically disengaged. Adolescents of these families reported the lowest levels of satisfaction. In the two last typologies, the flexibly chaotic and the cohesively disorganized, rigidity indicated a mid-range functionality as these families were characterized by emotional connectedness but lack of containment. Clinical implications are discussed
Acquisition of Relative Interstrand Crosslinker Resistance and PARP Inhibitor Sensitivity in Fanconi Anemia Head and Neck Cancers
PURPOSE: Fanconi anemia is an inherited disorder associated with a constitutional defect in the Fanconi anemia DNA repair machinery that is essential for resolution of DNA interstrand crosslinks. Individuals with Fanconi anemia are predisposed to formation of head and neck squamous cell carcinomas (HNSCC) at a young age. Prognosis is poor, partly due to patient intolerance of chemotherapy and radiation requiring dose reduction, which may lead to early recurrence of disease.
EXPERIMENTAL DESIGN: Using HNSCC cell lines derived from the tumors of patients with Fanconi anemia, and murine HNSCC cell lines derived from the tumors of wild-type and Fancc(-/-) mice, we sought to define Fanconi anemia-dependent chemosensitivity and DNA repair characteristics. We utilized DNA repair reporter assays to explore the preference of Fanconi anemia HNSCC cells for non-homologous end joining (NHEJ).
RESULTS: Surprisingly, interstrand crosslinker (ICL) sensitivity was not necessarily Fanconi anemia-dependent in human or murine cell systems. Our results suggest that the increased Ku-dependent NHEJ that is expected in Fanconi anemia cells did not mediate relative ICL resistance. ICL exposure resulted in increased DNA damage sensing and repair by PARP in Fanconi anemia-deficient cells. Moreover, human and murine Fanconi anemia HNSCC cells were sensitive to PARP inhibition, and sensitivity of human cells was attenuated by Fanconi anemia gene complementation.
CONCLUSIONS: The observed reliance upon PARP-mediated mechanisms reveals a means by which Fanconi anemia HNSCCs can acquire relative resistance to the ICL-based chemotherapy that is a foundation of HNSCC treatment, as well as a potential target for overcoming chemoresistance in the chemosensitive individual
Does normal processing provide evidence of specialised semantic subsystems?
Category-specific disorders are frequently explained by suggesting that living and non-living things are processed in separate subsystems (e.g. Caramazza & Shelton, 1998). If subsystems exist, there should be benefits for normal processing, beyond the influence of structural similarity. However, no previous study has separated the relative influences of similarity and semantic category. We created novel examples of living and non-living things so category and similarity could be manipulated independently. Pre-tests ensured that our images evoked appropriate semantic information and were matched for familiarity. Participants were trained to associate names with the images and then performed a name-verification task under two levels of time pressure. We found no significant advantage for living things alongside strong effects of similarity. Our results suggest that similarity rather than category is the key determinant of speed and accuracy in normal semantic processing. We discuss the implications of this finding for neuropsychological studies. © 2005 Psychology Press Ltd
Caudate nucleus volume mediates the link between cardiorespiratory fitness and cognitive flexibility in older adults
The basal ganglia play a central role in regulating the response selection abilities that are critical formental flexibility. In neocortical areas, higher cardiorespiratory fitness levels are associated with increased gray matter volume, and these volumetric differences mediate enhanced cognitive performance in a variety of tasks. Here we examine whether cardiorespiratory fitness correlates with the volume of the subcortical nuclei that make up the basal ganglia and whether this relationship predicts cognitive flexibility in older adults. Structural MRI was used to determine the volume of the basal ganglia nuclei in a group of older, neurologically healthy individuals (mean age 66 years, N = 179).Measures of cardiorespiratory fitness (VO2max), cognitive flexibility (task switching), and attentional control (flanker task) were also collected. Higher fitness levels were correlated with higher accuracy rates in the Task Switching paradigm. In addition, the volume of the caudate nucleus, putamen, and globus pallidus positively correlated with Task Switching accuracy.Nested regression modeling revealed that caudate nucleus volume was a significantmediator of the relationship between cardiorespiratory fitness, and task switching performance. These findings indicate that higher cardiorespiratory fitness predicts better cognitive flexibility in older adults through greater grey matter volume in the dorsal striatum
Plasticity of Brain Networks in a Randomized Intervention Trial of Exercise Training in Older Adults
Research has shown the human brain is organized into separable functional networks during rest and varied states of cognition, and that aging is associated with specific network dysfunctions. The present study used functional magnetic resonance imaging (fMRI) to examine low-frequency (0.008 < f < 0.08 Hz) coherence of cognitively relevant and sensory brain networks in older adults who participated in a 1-year intervention trial, comparing the effects of aerobic and non-aerobic fitness training on brain function and cognition. Results showed that aerobic training improved the aging brain's resting functional efficiency in higher-level cognitive networks. One year of walking increased functional connectivity between aspects of the frontal, posterior, and temporal cortices within the Default Mode Network and a Frontal Executive Network, two brain networks central to brain dysfunction in aging. Length of training was also an important factor. Effects in favor of the walking group were observed only after 12 months of training, compared to non-significant trends after 6 months. A non-aerobic stretching and toning group also showed increased functional connectivity in the DMN after 6 months and in a Frontal Parietal Network after 12 months, possibly reflecting experience-dependent plasticity. Finally, we found that changes in functional connectivity were behaviorally relevant. Increased functional connectivity was associated with greater improvement in executive function. Therefore the study provides the first evidence for exercise-induced functional plasticity in large-scale brain systems in the aging brain, using functional connectivity techniques, and offers new insight into the role of aerobic fitness in attenuating age-related brain dysfunction
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ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.
This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors
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