Drawing Conclusions: An Exploration of the Cognitive and Neuroscientific Foundations of Representational Drawing

The present thesis describes an exploration of cognitive, perceptual and neuroscientific foundations of representational drawing. To motivate experimental hypotheses, an initial qualitative study of artists’ attitudes and approaches to drawing was conducted. Themes from the qualitative data, predominantly concerning the relationship between perception and drawing, were developed into a large scale survey study of over 600 art students at undergraduate and postgraduate level. The survey study assessed the role of personality and demographic factors as well as perceptual styles and abilities, isolating the role of approaches to study, practice and technique use on externally-rated drawing ability. The qualitative and survey studies provided the foundation for further empirical work, the first of which was an exploration of the use of image manipulation and shape analysis for measuring the accuracy of drawings, with the intention of providing more reliable and valid dependent measures in the study of drawing. This investigation revealed differences in the way individuals judge the accuracy of drawings according to the stimuli they represent and presents a novel method for comparing aesthetic and accuracy judgments of drawing. The three experimental chapters of this thesis describe investigations into visual perception and memory in association with drawing in students of arts and non-arts subjects with an emphasis on angular/proportional perception, local-global visual processing and long and short-term visual memory. These studies revealed that individual differences in visual perception and visual long-term memory when rendering explain a large proportion of individual differences in drawing ability. The final empirical chapter reports a voxel-based morphometry study of structural neural correlates with individual differences in drawing and artistic ability. The results of this study emphasize the role of procedural memory and fine motor control in the development of long-term drawing expertise. The enquiry culminates in the presentation of a toolbox for drawing which includes visual, educational and motor modules. Its potential use in art and design education in teaching protocol is then discussed. The research findings could have a significant impact on the way in which art schools employ artistic training and could provide early diagnostic tools for identifying talent in the arts

Therapeutic limitations in tumor-specific CD8+ memory T cell engraftment

BACKGROUND: Adoptive immunotherapy with cytotoxic T lymphocytes (CTL) represents an alternative approach to treating solid tumors. Ideally, this would confer long-term protection against tumor. We previously demonstrated that in vitro-generated tumor-specific CTL from the ovalbumin (OVA)-specific OT-I T cell receptor transgenic mouse persisted long after adoptive transfer as memory T cells. When recipient mice were challenged with the OVA-expressing E.G7 thymoma, tumor growth was delayed and sometimes prevented. The reasons for therapeutic failures were not clear. METHODS: OT-I CTL were adoptively transferred to C57BL/6 mice 21 – 28 days prior to tumor challenge. At this time, the donor cells had the phenotypical and functional characteristics of memory CD8+ T cells. Recipients which developed tumor despite adoptive immunotherapy were analyzed to evaluate the reason(s) for therapeutic failure. RESULTS: Dose-response studies demonstrated that the degree of tumor protection was directly proportional to the number of OT-I CTL adoptively transferred. At a low dose of OT-I CTL, therapeutic failure was attributed to insufficient numbers of OT-I T cells that persisted in vivo, rather than mechanisms that actively suppressed or anergized the OT-I T cells. In recipients of high numbers of OT-I CTL, the E.G7 tumor that developed was shown to be resistant to fresh OT-I CTL when examined ex vivo. Furthermore, these same tumor cells no longer secreted a detectable level of OVA. In this case, resistance to immunotherapy was secondary to selection of clones of E.G7 that expressed a lower level of tumor antigen. CONCLUSIONS: Memory engraftment with tumor-specific CTL provides long-term protection against tumor. However, there are several limitations to this immunotherapeutic strategy, especially when targeting a single antigen. This study illustrates the importance of administering large numbers of effectors to engraft sufficiently efficacious immunologic memory. It also demonstrates the importance of targeting several antigens when developing vaccine strategies for cancer

The use of curved vs. straight instruments in single port access surgery, on standardized box trainer tasks

BACKGROUND: Single-port access (SPA) surgery is a novel surgical technique to create nearly "scarless" surgery. SPA surgery appears to be safe and feasible, but the exposure and handling of tissue may not be optimal. Therefore, the performance of SPA surgery with different instruments used and conventional laparoscopy is compared. METHODS: Fifteen participants (>50 laparoscopic procedures) performed three basic tasks (translocation, clip & cut, and tissue dissection, based on the fundamentals of laparoscopic surgery) in the box trainer in laparoscopy and SPA settings with both (conventional) crossed and curved instruments. All participants completed a questionnaire, which asked their opinion on the use of instruments and preference. RESULTS: Translocation was performed significantly faster in both laparoscopy and SPA crossed than SPA curved (means, 130.3 and 137.7 vs. 170.7 sec; p < 0.001 and p = 0.005). The errors also were less in laparoscopy and SPA crossed (means, 0.9 and 1.2 vs. 1.6), but not significant. The time to complete the dissection was almost equal between laparoscopy and SPA curved settings, but took longer for SPA crossed, although not significantly (148.1 and 150.8 vs. 179.5 sec). The errors only differed significantly between laparoscopy and SPA crossed (means, 0.5 vs. 1.27; p = 0.044). Fourteen participants still favored conventional laparoscopy and one SPA curved. They also thought SPA curved was better than crossed (means, 3.6 vs. 2.47; p = 0.003) and that exposure is superior in curved (means, 3.4 vs. 2.27; p = 0.002). CONCLUSIONS: Although conventional laparoscopy may appear most effective for proper dissection and exposure of tissue, single-port access surgery shows potential. Especially in the tissue dissection task, there is no significant difference in time or errors between conventional laparoscopy and SPA surgery, using specially designed curved instruments. Although the participants favor conventional laparoscopy, this could evolve to a more accepting mind when SPA surgery becomes more available and used in the clinical setting

Social networks and implementation of evidence-based practices in public youth-serving systems: a mixed-methods study

<p>Abstract</p> <p>Background</p> <p>The present study examines the structure and operation of social networks of information and advice and their role in making decisions as to whether to adopt new evidence-based practices (EBPs) among agency directors and other program professionals in 12 California counties participating in a large randomized controlled trial.</p> <p>Methods</p> <p>Interviews were conducted with 38 directors, assistant directors, and program managers of county probation, mental health, and child welfare departments. Grounded-theory analytic methods were used to identify themes related to EBP adoption and network influences. A web-based survey collected additional quantitative information on members of information and advice networks of study participants. A mixed-methods approach to data analysis was used to create a sociometric data set (n = 176) for examination of associations between advice seeking and network structure.</p> <p>Results</p> <p>Systems leaders develop and maintain networks of information and advice based on roles, responsibility, geography, and friendship ties. Networks expose leaders to information about EBPs and opportunities to adopt EBPs; they also influence decisions to adopt EBPs. Individuals in counties at the same stage of implementation accounted for 83% of all network ties. Networks in counties that decided not to implement a specific EBP had no extra-county ties. Implementation of EBPs at the two-year follow-up was associated with the size of county, urban versus rural counties, and in-degree centrality. Collaboration was viewed as critical to implementing EBPs, especially in small, rural counties where agencies have limited resources on their own.</p> <p>Conclusions</p> <p>Successful implementation of EBPs requires consideration and utilization of existing social networks of high-status systems leaders that often cut across service organizations and their geographic jurisdictions.</p> <p>Trial Registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00880126">NCT00880126</a></p

Prognostic significance of HER3 and HER4 protein expression in colorectal adenocarcinomas

BACKGROUND: Colorectal cancer remains a major cause of cancer mortality in the Western world. A limited number of studies has been conducted in respect of Her-3 and Her-4 expression and their correlation with clinical parameters and prognosis in colorectal carcinomas . In this study we sought to determine the pattern and the prognostic significance of HER-3 and HER-4 in colorectal adenocarcinoma. METHODS: We studied HER-3 and HER-4 protein expression in106 paraffin embedded specimens of primary colorectal tumors using immunohistochemistry. The pattern and protein expression levels of HER-3 and HER-4 were correlated with several clinical and pathological parameters. RESULTS: HER-3 staining displayed membranous and cytoplasmic expression pattern in 18 (17%) and 30 samples (28,3%), respectively. HER-4 membranous and cytoplasmic expression was found in 20 (18,9%) and 32 samples (30,2%), respectively. Specimens regarded as positive for HER-3 cytoplasmic expression were associated with moderate tumor grade (p = 0,032) and older median age (p = 0,010). Specimens regarded as positive for HER-4 membranous protein expression were associated with involved lymphnodes (p = 0,0003). Similar results were obtained when considering Her-3 and Her-4 protein expression irrespective of their cellular localization. There was no correlation between the expression of HER-3 and HER-4 and patients outcome. CONCLUSION: HER-4 membranous protein expression was found to predict for lymph nodes positivity in this cohort of patients with colorectal cancer.HER-4 expression status may identify tumors with aggressive biological behavior and increased metastatic potential

Dimensionality of Carbon Nanomaterials Determines the Binding and Dynamics of Amyloidogenic Peptides: Multiscale Theoretical Simulations

Experimental studies have demonstrated that nanoparticles can affect the rate of protein self-assembly, possibly interfering with the development of protein misfolding diseases such as Alzheimer's, Parkinson's and prion disease caused by aggregation and fibril formation of amyloid-prone proteins. We employ classical molecular dynamics simulations and large-scale density functional theory calculations to investigate the effects of nanomaterials on the structure, dynamics and binding of an amyloidogenic peptide apoC-II(60-70). We show that the binding affinity of this peptide to carbonaceous nanomaterials such as C60, nanotubes and graphene decreases with increasing nanoparticle curvature. Strong binding is facilitated by the large contact area available for π-stacking between the aromatic residues of the peptide and the extended surfaces of graphene and the nanotube. The highly curved fullerene surface exhibits reduced efficiency for π-stacking but promotes increased peptide dynamics. We postulate that the increase in conformational dynamics of the amyloid peptide can be unfavorable for the formation of fibril competent structures. In contrast, extended fibril forming peptide conformations are promoted by the nanotube and graphene surfaces which can provide a template for fibril-growth