On Embedding Indigenous Musics in Schools: Examining the Applicability of Possible Models to One School District's Approach.

Recent curriculum policy changes in British Columbia (BC) require that educators in all subject areas-including music-embed local Indigenous knowledge, pedagogies, and worldviews in their classes. Yet facilitating such decolonizing cross-cultural music education activities requires knowledge that music educators may not currently possess. We use four models created by an Indigenous Arts scholar to examine the interface of Indigenous and Western art musics in performing arts settings: (a) integration, (b) nation-to-nation music trading and reciprocal presentation, (c) a combination of the first two models, and (d) non-integrative encounters that are in relationship but have irreconcilable elements.

Here today, gone tomorrow: Outcomes of residual leak following secundum atrial septal defect closure with the GORE CARDIOFORM Septal Occluder.

Objective: To assess the outcomes and potential predictors of residual leak after implantation of the GORE CARDIOFORM Septal Occluder (GSO) in secundum atrial septal defects (ASDs).

Background: The non-self-centering design of the GSO could lead to residual leak at the edge of the device. Outcomes of residual leak are poorly understood.

The Potential Effect of the 21st Century Cures Act on Drug Development.

Unlabelled: Enacted in December 2016, the 21st Century Cures Act is a pivotal piece of legislation that will influence the FDA drug and device approval process for the foreseeable future. Although this legislation received overwhelming support by members of Congress for much needed budgetary increases for the FDA and other national health organizations, there is much controversy over certain provisions that potentially diminish the robustness of the evidence base required for drug and medical device approvals. This article discusses the key provisions from "Title III - Development" under "Division A - 21st Century Cures" related to drug development and, specifically, explores those aspects that address patient-focused drug development, use of surrogate endpoints in clinical trials, modernization of trial design, and use of real-world evidence for decision making and health care economic information.

Evaluating Oncology Value-Based Frameworks in the U.S. Marketplace and Challenges in Real-World Application: A Multiple Myeloma Test Case.

Background: With the continuous rise in costs for oncology drugs, the American Society of Clinical Oncology (ASCO), the Institute for Clinical and Economic Review (ICER), the Memorial Sloan Kettering Cancer Center's Drug Abacus (DrugAbacus), and the National Comprehensive Cancer Network (NCCN) have developed value-based frameworks (VBFs) to assist stakeholders in formulary and treatment decision-making processes. Since emerging VBFs have the potential to affect available treatment options for patients, it is important to understand the differences associated with these VBFs within various therapeutic areas.

Objectives: To (a) compare VBFs across 3 therapeutic options for relapsed or refractory multiple myeloma (RRMM) and (b) identify challenges and limitations associated with real-world decision making using VBFs in the U.

Performance-Based Risk-Sharing Arrangements: U.S. Payer Experience.

Background: As a result of global concern about rising drug costs, many U.S. payers and European agencies such as the National Health Service have partnered with pharmaceutical companies in performance-based risk-sharing arrangements (PBRSAs) by which manufacturers share financial risk with health care purchasing entities and authorities.

The challenges surrounding preclinical testing in transcatheter device development and the implications on the clinic.

Transcatheter devices have contributed significantly to the advances achieved in treating many cardiovascular conditions over the last few decades. Sophisticated and detailed preclinical testing is not only a regulatory requirement to support an investigational device exemption (IDE) application, but more crucially its success and accuracy is needed to safeguard patients during the subsequent clinical testing stages. Areas covered: This article covers the regulatory background as well as specific considerations related to pre-clinical testing of transcatheter devices.

Point-of-Care Testing.

This article provides an overview of the current use of point-of-care testing (POCT) and its utility for patients' self-management of chronic disease states. Pharmacists utilize POCT to provide rapid laboratory diagnostic results as a monitoring tool in the management of their patients and in order to improve medication outcomes. Considerations for the transition to use of POCT in the home to further improve disease management and improve health care cost-effectiveness are discussed.

Exploring DOXP-reductoisomerase binding limits using phosphonated N-aryl and N-heteroarylcarboxamides as DXR inhibitors.

DOXP-reductoisomerase (DXR) is a validated target for the development of antimalarial drugs to address the increase in resistant strains of Plasmodium falciparum. Series of aryl- and heteroarylcarbamoylphosphonic acids, their diethyl esters and disodium salts have been prepared as analogues of the potent DXR inhibitor fosmidomycin. The effects of the carboxamide N-substituents and the length of the methylene linker have been explored using in silico docking studies, saturation transfer difference NMR spectroscopy and enzyme inhibition assays using both EcDXR and PfDXR.

Combined prospective United States clinical study data for the GORE(®) HELEX(®) septal occluder device.

Objectives: Our goal was to summarize the outcome for all subjects evaluated during a prospective clinical study in the United States with the GORE(®) HELEX(®) Septal Occluder for transcatheter repair of secundum atrial septal defects (ASD).

Background: The GORE(®) HELEX(®) Septal Occluder is currently utilized for repair of secundum ASD. No previous reports are available that summarize the combined clinical trial outcomes for this device.

The druggable antimalarial target PfDXR: overproduction strategies and kinetic characterization.

Plasmodium falciparum 1-deoxy-D-xylulose-5-phosphate reductoisomerase (PfDXR) is a key enzyme in the synthesis of isoprenoids in the malaria parasite, using a pathway that is absent in the human host. This enzyme is receiving attention as it has been validated as a promising drug target. However, an impediment to the characterisation of this enzyme has been the inability to obtain sufficient quantities of the enzyme in a soluble and functional form.

Galectin-1, a gene preferentially expressed at the tumor margin, promotes glioblastoma cell invasion.

Background: High-grade gliomas, including glioblastomas (GBMs), are recalcitrant to local therapy in part because of their ability to invade the normal brain parenchyma surrounding these tumors. Animal models capable of recapitulating glioblastoma invasion may help identify mediators of this aggressive phenotype.

Methods: Patient-derived glioblastoma lines have been propagated in our laboratories and orthotopically xenografted into the brains of immunocompromized mice.

The role of vision, speed, and attention in overcoming directional biases during arm movements.

Previous research has revealed directional biases (preferences to select movements in specific directions) during horizontal arm movements with the use of a free-stroke drawing task. The biases were interpreted as a result of a tendency to generate motion at either the shoulder or elbow (leading joint) and move the other (subordinate) joint predominantly passively to avoid neural effort for control of interaction torque. Here, we examined influence of vision, movement speed, and attention on the directional biases.

The role of intrinsic factors in control of arm movement direction: implications from directional preferences.

The role of extrinsic and intrinsic factors in control of arm movement direction remains under debate. We addressed this question by investigating preferences in selection of movement direction and whether factors causing these preferences have extrinsic or intrinsic nature. An unconstrained free-stroke drawing task was used during which participants produced straight strokes on a horizontal table, choosing the direction and the beginning and end of each stroke arbitrarily.

Failure of the GORE HELEX atrial septal defect occluder to treat membranous VSDs in swine.

Objective: We tested the suitability of the GORE HELEX septal occluder for closure of membranous ventricular septal defect in three Yucatan minipigs that had naturally-occurring membranous ventricular septal defects.

Methods: The animals were studied in the Gore Science Center Laboratory in Flagstaff, Arizona. In all of the device implantations, seating of the right disk along the right ventricular septum was problematic with resultant entanglement of one device in the chordae tendinae during attempted removal, implantation of one device onto the tricuspid valve papillary muscle and unlocking of one device occurring after implantation.

Malaria heat shock proteins: drug targets that chaperone other drug targets.

Ongoing research into the chaperone systems of malaria parasites, and particularly of Plasmodium falciparum, suggests that heat shock proteins (Hsps) could potentially be an excellent class of drug targets. The P. falciparum genome encodes a vast range and large number of chaperones, including 43 Hsp40, six Hsp70, and three Hsp90 proteins (PfHsp40s, PfHsp70s and PfHsp90s), which are involved in a number of fundamental cellular processes including protein folding and assembly, protein translocation, signal transduction and the cellular stress response.

The malarial drug target Plasmodium falciparum 1-deoxy-D-xylulose-5-phosphate reductoisomerase (PfDXR): development of a 3-D model for identification of novel, structural and functional features and for inhibitor screening.

A three-dimensional model of the malarial drug target protein PfDXR was generated, and validated using structure-checking programs and protein docking studies. Structural and functional features unique to PfDXR were identified using the model and comparative sequence analyses with apicomplexan and non-apicomplexan DXR proteins. Furthermore, we have used the model to develop an efficient approach to screen for potential tool compounds for use in the rational design of novel DXR inhibitors.

PTEN loss does not predict for response to RAD001 (Everolimus) in a glioblastoma orthotopic xenograft test panel.

Purpose: Hyperactivation of the phosphatidylinositol 3-kinase/Akt signaling through disruption of PTEN function is common in glioblastoma multiforme, and these genetic changes are predicted to enhance sensitivity to mammalian target of rapamycin (mTOR) inhibitors such as RAD001 (everolimus).

Experimental Design: To test whether PTEN loss could be used as a predictive marker for mTOR inhibitor sensitivity, the response of 17 serially transplantable glioblastoma multiforme xenografts was evaluated in an orthotopic therapy evaluation model. Of these 17 xenograft lines, 7 have either genomic deletion or mutation of PTEN.

Directional biases reveal utilization of arm's biomechanical properties for optimization of motor behavior.

Strategies used by the CNS to optimize arm movements in terms of speed, accuracy, and resistance to fatigue remain largely unknown. A hypothesis is studied that the CNS exploits biomechanical properties of multijoint limbs to increase efficiency of movement control. To test this notion, a novel free-stroke drawing task was used that instructs subjects to make straight strokes in as many different directions as possible in the horizontal plane through rotations of the elbow and shoulder joints.

Retargeted oncolytic measles strains entering via the EGFRvIII receptor maintain significant antitumor activity against gliomas with increased tumor specificity.

Among the best-characterized genetic alterations in gliomas is the amplification of the epidermal growth factor receptor (EGFR) gene, present in approximately 40% of glioblastoma multiforme, and frequently associated with the EGFRvIII gene rearrangement. We have previously shown that attenuated vaccine strains of measles virus have potent antitumor activity against gliomas, and identified H protein mutations, which ablate recognition of the natural measles virus receptors CD46 and SLAM. Retargeted recombinant viruses were generated from the measles Edmonston-NSe vaccine strain displaying a single-chain antibody against EGFRvIII at the COOH terminus of H and containing the marker green fluorescent protein (GFP) gene in position 1.

Disruption of parallel and converging signaling pathways contributes to the synergistic antitumor effects of simultaneous mTOR and EGFR inhibition in GBM cells.

Elevated epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR) signaling are known to contribute to the malignant properties of glioblastoma multiforme (GBM), which include uncontrolled cell proliferation and evasion of apoptosis. Small molecule inhibitors that target these protein kinases have been evaluated in multiple clinical trials for cancer patients, including those with GBM. Here we have examined the cellular and molecular effects of a combined kinase inhibition of mTOR (rapamycin) and EGFR (EKI-785) in U87 and U251 GBM cells.

Enterprise-wide worklist management.

Radiologists in multi-facility health care delivery networks must serve not only their own departments but also departments of associated clinical facilities. We describe our experience with a picture archiving and communication system (PACS) implementation that provides a dynamic view of relevant radiological workload across multiple facilities. We implemented a distributed query system that permits management of enterprise worklists based on modality, body part, exam status, and other criteria that span multiple compatible PACSs.

A genetic animal model of human neocortical heterotopia associated with seizures.

Malformations of the human neocortex are commonly associated with developmental delays, mental retardation, and epilepsy. This study describes a novel neurologically mutant rat exhibiting a forebrain anomaly resembling the human neuronal migration disorder of double cortex. This mutant displays a telencephalic internal structural heterotopia (tish) that is inherited in an autosomal recessive manner.

A noninvasive thermoplastic head immobilization system. Technical note.

The authors have developed a noninvasive head immobilization system for use in neuroimaging (magnetic resonance imaging, computerized tomography, single photon emission computerized tomography, and projection angiography), neurosurgical planning, and neurosurgery. These diagnostic and surgical procedures require patient immobilization, reproducible patient positioning, and anatomical localization. The thermoplastic system described in this technical note addresses each of these requirements with a high degree of accuracy and with no bone fixation.

Stereotactic laser-guided approach to distal middle cerebral artery aneurysms.

The Steiner-Lindquist laser intra-operative guidance method is described and its application in the surgical treatment of mycotic aneurysm is presented. Three illustrative cases of distal middle cerebral artery aneurysms are reported. The authors argue that all ruptured mycotic aneurysms should be treated surgically.

ACT3: a high-speed, high-precision electrical impedance tomograph.

This paper presents the design, implementation, and performance of Rensselaer's third-generation Adaptive Current Tomograph, ACT3. This system uses 32 current sources and 32 phase-sensitive voltmeters to make a 32-electrode system that is capable of applying arbitrary spatial patterns of current. The instrumentation provides 16 b precision on both the current values and the real and reactive voltage readings and can collect the data for a single image in 133 ms.