What Influences Educators’ Design Preferences for Bullying Prevention Programs? Multi-level Latent Class Analysis of a Discrete Choice Experiment

School Mental Health - We used a discrete choice conjoint experiment to model the anti-bullying (AB) program preferences of 1080 junior kindergarten to Grade 8 educators. Participants chose between...     

High-throughput molecular and histopathologic profiling of tumor tissue in a novel transplantable model of murine neuroblastoma: new tools for pediatric drug discovery

Using two MYCN transgenic mouse strains, we established 10 transplantable neuroblastoma cell lines via serial orthotopic passage in the adrenal gland. Tissue arrays demonstrate that by histochemistry, vascularity, immunohistochemical staining for neuroblastoma markers, catecholamine analysis, and concurrent cDNA microarray analysis, there is a close correspondence between the transplantable lines and the spontaneous tumors. Several genes closely associated with the pathobiology and immune evasion of neuroblastoma, novel targets that warrant evaluation, and decreased expression of tumor suppressor genes are demonstrated. These studies describe a unique and generalizable approach to expand the utility of transgenic models of spontaneous tumor, providing new tools for preclinical investigation.     

Modeling the Problem-based Learning Preferences of McMaster University Undergraduate Medical Students Using a Discrete Choice Conjoint Experiment

Objectives: To use methods from the field of marketing research to involve students in the redesign of McMaster University’s small group, problem-based undergraduate medical education program. Methods: We used themes from a focus group conducted in an electronic decision support lab to compose 14 four-level educational attributes. Undergraduate medical students completed a discrete choice experiment composed of 15 web-administered, partial-profile, conjoint-choice tasks. Results: Latent class analysis revealed two segments with different preferences. Segment 1, (86% of students), preferred a problem-based approach with more small group tutorial sessions led by expert tutors who facilitated the tutorial process without teaching didactically. Segment 2, (14% of students), preferred more large group lectures, explicit learning objectives, expert tutors who taught didactically, and streaming options based on learning preferences. Although Segment 1 preferred smaller tutorial groups, simulations predicted these students would trade increases in tutorial group size for a conceptually integrated program that included tutorial problems based on core curriculum concepts, greater integration of the content of clinical skills training sessions and the tutorial curriculum, and a link between clerkship patient selection and the program’s curriculum. A majority of both segments would accept a more conceptually integrated program if the savings associated with increases in tutorial group size was reinvested in web-enhanced tutorial processes and computer-simulated health care problems. Conclusions: Most students preferred a small group, web-supported, problem-based learning approach led by content experts who facilitated group process. Students favored a program in which tutorial group problems, clinical skills training sessions and the patients selected for clerkship activities were more closely linked to core curriculum concepts.     

Finite element analysis of stresses in the maxillary and mandibular dental arches and TMJ articular discs during clenching into maximum intercuspation, anterior and unilateral posterior occlusion

The objective of this study was to investigate distribution of stresses in the human TMJ discs, generated during clenching into various occlusal positions. The work presents a biomechanical finite element model of interaction of mandibular and maxillary dental arches and the TMJ discs of a particular person, based on real geometrical data obtained from spiral computed tomography two-dimensional images. 3D contour coordinates - point clouds were collected from these images and solid model was created. The system under investigation consisted of eight basic parts: two rigid structures representing the mandibular and maxillary dental arches, two mandibular condyles, two mandibular fossae of temporal bone, and solid models of two articular discs. The model of maxillary dental arch was fixed in space. The model of the mandibular dental arch was able to move in space synchronically with the mandibular condyles under action of applied forces, which were considered as prescribed and known at insertion points of masticatory muscles. The motion of the mandible was constrained by interdental contact interactions and contact interaction with articular discs, which were situated in between mandibular condyles and mandibular fossae of temporal bone. The model was implemented by using LS-DYNA finite element software. The obtained results presented a 3D view of stresses exhibited in the articular discs, as well as the real contact points of dental interactions at given masticatory geometry of a particular subject and the values of interaction forces. The expected practical value of the developed model is the facilitation of biomechanical evaluations of the influence of tolerances of teeth shapes and occlusal areas together with the supporting areas on the final stress distribution in the dental arches and articular discs.     

Molecular heterogeneity in glioblastoma: therapeutic opportunities and challenges

Glioblastoma (GBM) has been recognized as a clinical and pathologic entity for more than a century. Throughout its history, its cells of origin have been in question. Its behavior is aggressive and despite decades of effort, median survival is just beginning to improve. Surgical techniques and radiotherapy schemas continue to be refined, but the most recent progress has been achieved through improved medical therapies. These are the result of both pharmacological advances and a deeper understanding of the biological characteristics of GBM. Due to a combination of its complex phenotype and organ-specific clinical manifestations, efforts to refine GBM treatment with targeted therapies largely have been frustrated. In this review, we discuss recent attempts to exploit new molecular insights, consider the reasons for slow progress in developing better treatments, and examine future therapeutic options.     

Ocular melanoma metastasis to the cervical spine

Ocular melanoma is a rare type of malignant melanoma. Melanoma metastatic to the spine typically arises within the vertebral column, presents with back pain, and has a poor prognosis. We present a patient with a unique disease course: ocular melanoma metastasis occurred after an extended latency period of 14 years, attained a large size within the spinal intradural space, presented with severe neurological deficits without additional central nervous system disease, and the tumor was amenable to surgical intervention. We also review the literature on melanoma spine metastasis.     

The future is now: chimeric antigen receptors as new targeted therapies for childhood cancer

Improved outcomes for children with cancer hinge on the development of new targeted therapies with acceptable short-term and long-term toxicity. Progress in basic, preclinical, and clinical arenas spanning cellular immunology, gene therapy, and cell-processing technologies have paved the way for clinical applications of chimeric antigen receptor-based therapies. This is a new form of targeted immunotherapy that merges the exquisite targeting specificity of monoclonal antibodies with the potent cytotoxicity, potential for expansion, and long-term persistence provided by cytotoxic T cells. Although this field is still in its infancy, clinical trials have already shown clinically significant antitumor activity in neuroblastoma, chronic lymphocytic leukemia, and B-cell lymphoma, and trials targeting a variety of other adult and pediatric malignancies are under way. Ongoing work is focused on identifying optimal tumor targets and elucidating and manipulating both cell- and host-associated factors to support expansion and persistence of the genetically engineered cells in vivo. In pediatric oncology, CD19 and GD2 are compelling antigens that have already been identified for targeting pre-B acute lymphoblastic leukemia and neuroblastoma, respectively, with this approach, but it is likely that other antigens expressed in a variety of childhood cancers will also soon be targeted using this therapy. The potential to target essentially any tumor-associated cell-surface antigen for which a monoclonal antibody can be made opens up an entirely new arena for targeted therapy of childhood cancer.     

Incidence and precipitating factors of delirium after coronary artery bypass grafting

Objective. To analyze large contemporary patient population, undergoing on-pump coronary artery bypass grafting at our institution, and identify the prevalence and precipitating factors of delirium development. Design. Baseline demographics, operative data and postoperative outcomes of 1367 consecutive patients were recorded prospectively and analysed using multivariate logistic regression analysis, to determine independent predictors of postoperative delirium development. Results. Delirium was detected in 42 (3.07%) patients. Eight factors: age more than 65 years, peripheral vascular disease, Euroscore≥5, preoperative IABP support, postoperative blood product usage and postoperative low cardiac output syndrome were independently predicting delirium development after coronary artery bypass procedures. Postoperative delirium was associated with significantly higher mortality rate (16.6% vs. 3.9%, p=0.013), prolonged mechanical ventilation time (9.2±3.1 vs. 5.05±7.6, p=0.04) and increased length of intensive care unit stay (6.8±4.9 vs. 2.0±2.7 days, p=0.001). Conclusions. Delirium is a dangerous complication, prolonging intensive care unit stay and postoperative mortality. Factors associated with delirium development are advanced age, peripheral vascular disease, diminished cardiac function and blood product usage.