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Elementary music specialists teach all students in all grades at their schools, which requires the preparation of a variety of lessons simultaneously. As a result of seeing 100% of the student population, elementary music teachers host more students with disabilities than a general classroom teacher would in their class. Depending on the severity of students' disabilities, some students require alterations to general music lessons. In this study, we surveyed regional elementary music teachers (N = 15) to discover what disabilities were prevalent in their classes and if activities were adjusted. By examining the characteristics of the disabilities listed in the Individuals with Disabilities Education Act, we split disabilities into three groups: physical, cognitive, and emotional and behavioral disabilities. We surveyed elementary music educators on the prevalence of disabilities in their classrooms, to what degree educators adjusted their instruction for those students, and whether growth was seen in those students through musical instruction. Results revealed that all educators tailored their instruction in some way to serve students with disabilities. Educators mostly adjusted in the planning beforehand and while teaching their students. The most overall growth (musical, academic, and social) was seen in students with emotional and behavioral disabilities. Further research is needed in elementary music curriculum adaptation and modification, including pre-service and in-service music teacher training in working with students with disabilities.

High temperature (200-260°C) military composite engine components made of carbon fiber thermoset materials are susceptible to erosion damage. Evidenced by wear seen during operation, erosion protection remains a challenge for composites in the engine air flow path. In this paper, we investigate polyetheretherketone (PEEK), thermoplastic polyimide (TPI), and ceramic fabric (Nextel™) as potential high temperature erosion coatings for thermoset polyimide composite engine components. We evaluate the erosion protection materials for two qualities: (1) co-moldability with thermoset polyimide composite panels, and (2) erosion resistance to a sandblasting test. Autoclave and compression molding were used to test co-moldability with different manufacturing methods. The compression molding process was optimized to reduce surface defects using a pre-imidization step before the erosion protection layer was applied and final cure was completed. Comolded test panels were cut into small coupons for sandblasting. After 60 s of alumina sandblasting PEEK had negligible mass loss, whereas the TPI and ceramic fabric had roughly the same erosion rate as the uncoated polyimide laminate. [ABSTRACT FROM AUTHOR]

Many engineering courses rely on in-person lectures and textbooks for content delivery, with homework sets and exams for evaluating and reinforcing student progress. Yet some research studies have shown that exams--high-pressure, time-limited assessments--are detrimental to the learning process and unnecessarily increase students' stress. We describe a new student-centered teaching approach based on four pedagogical domains: scaffolded, universally-designed, mastery-based, and gameful learning. The approach was implemented in an engineering course by first chunking the content into small, easily digestible topics. Next, multiple modalities were used to deliver this content, including textbook references, virtual lectures, condensed presentation slides, summary sheets, and two-minute videos. Finally, the typical grading system was replaced by a point system using multiple 10- and 20-point quizzes, all of which could be attempted multiple times through unique versions for each student. Several findings emerged from our examination of this overall instructional strategy. The flexibility in learning and assessment enhanced students' mastery of content and maximized their sense of ownership in the learning process. The multiple attempts on quizzes provided the students with more freedom to fail and resulted in a more supportive learning environment. Last, the multimodal delivery and self-controlled assessment process promoted inclusive and equitable learning. This course structure can be translated to many other engineering courses, with spreadsheets and a web-based quiz making program developed to assist in the process. [ABSTRACT FROM AUTHOR]

Background Given the multifaceted nature of the balance system, an interdisciplinary approach to patient care is imperative. For surgical patients with complex medical histories, comprehensive vestibular evaluations provide information on baseline vestibular function and identify possible surgical risks and outcomes. This case study follows a patient diagnosed with probable right vestibular neuronitis immediately preceding surgical resection of a left brainstem lesion, later diagnosed as a B cell lymphoma (BCL) and provides details regarding pre- and postsurgical outcomes. Purpose This case study expands on the importance of the inclusion of vestibular audiologists on the interdisciplinary team for related surgical procedures to provide insight into possible surgical risks and subsequent effects on patients' postsurgical quality of life. Research Design Case report. Study Sample A 68-year-old female patient evaluated within the Henry Ford Health System for management of diffuse large BCL. Data Collection Standard neuro-otology, neuro-surgical, audiological, and vestibular evaluations were conducted to evaluate the patient's complex symptomology. Results This case report outlines a patient hospitalized for a left brainstem mass, later diagnosed as an aggressive form of lymphoma, with a concurrent episode of vestibular neuronitis on the contralesional side. Functional outcomes are discussed following surgical intervention to remove the mass. Postsurgical vestibular testing revealed a bilateral vestibular hypofunction. Conclusions Vestibular audiology plays an essential role in the multidisciplinary team for complex dizzy patients with related surgical procedures, as this subset of the field can offer critical insight into postsurgical recommendations and patient expectations. [ABSTRACT FROM AUTHOR]

As pancreatic cancer is the third deadliest cancer in the U.S., the ability to study genetic alterations is necessary to provide further insight into potentially targetable regions for cancer treatment. Circulating tumor cells (CTCs) represent an especially aggressive subset of cancer cells, capable of causing metastasis and progressing the disease. Here, we present the Labyrinth–DEPArray pipeline for the isolation and analysis of single CTCs. Established cell lines, patient-derived CTC cell lines and freshly isolated CTCs were recovered and sequenced to reveal single-cell copy number variations (CNVs). The resulting CNV profiles of established cell lines showed concordance with previously reported data and highlight several gains and losses of cancer-related genes such as FGFR3 and GNAS. The novel sequencing of patient-derived CTC cell lines showed gains in chromosome 8q, 10q and 17q across both CTC cell lines. The pipeline was used to process and isolate single cells from a metastatic pancreatic cancer patient revealing a gain of chromosome 1q and a loss of chromosome 5q. Overall, the Labyrinth-DEPArray pipeline offers a validated workflow combining the benefits of antigen-free CTC isolation with single cell genomic analysis. [ABSTRACT FROM AUTHOR]

Microfluidic devices are typically fabricated in an expensive, multistep process (e.g., photolithography, etching, and bonding). Additive manufacturing (AM) has emerged as a revolutionary technology for simple and inexpensive fabrication of monolithic structures—enabling microfluidic designs that are challenging, if not impossible, to make with existing fabrication techniques. Here, we introduce volumetric stereolithography (vSLA), an AM method in which polymerization is constrained to specific heights within a resin vat, allowing layer-by-layer fabrication without a moving platform. vSLA uses an existing dual-wavelength chemistry that polymerizes under blue light (λ = 458 nm) and inhibits polymerization under UV light (λ = 365 nm). We apply vSLA to fabricate microfluidic channels with different spatial and vertical geometries in less than 10 min. Channel heights ranged from 400 μm to 1 mm and could be controlled with an optical dose, which is a function of blue and UV light intensities and exposure time. Oxygen in the resin was found to significantly increase the amount of dose required for curing (i.e., polymerization to a gelled state), and we recommend that an inert vSLA system is used for rapid and reproducible microfluidic fabrication. Furthermore, we recommend polymerizing far beyond the gel point to form more rigid structures that are less susceptible to damage during post-processing, which can be done by simultaneously increasing the blue and UV light absorbance of the resin with light intensities. We believe that vSLA can simplify the fabrication of complex multilevel microfluidic devices, extending microfluidic innovation and availability to a broader community. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) are extremely rare cells shed from tumors into the blood stream. These cells can provide valuable information about their tumor of origin and direct treatment decisions to improve patient outcomes. Current technologies isolate CTCs from a limited blood volume and often require pre-processing that leads to CTC loss, making it difficult to isolate enough CTCs to perform in-depth tumor analysis. Many inertial microfluidic devices have been developed to isolate CTCs at high flow rates, but they typically require either blood dilution, pre-processing to remove red blood cells, or a sheath buffer rather than being able to isolate cells directly from whole blood. To decrease the need for pre-processing while increasing CTC yield, we developed an inertial device, the CTCKey™, to focus CTCs in whole blood at high throughput yielding a concentrated product stream enriched for CTCs. The CTCKey™ consists of two sections to create CTC enriched blood that can be further processed using any CTC isolation device to selectively isolate the CTCs. A thorough analysis was performed using the MCF7 breast cancer cell line spiked into bovine serum albumin (BSA) solutions of varying concentrations, as well as whole blood to characterize the focusing patterns of the CTCKey™. At the optimal flow rate of 2.4 mL min−1, the CTCKey™ reduces the CTC containing blood volume by 78%; the CTCs from 1 mL of blood are now in 0.22 mL of blood. The CTCKey's™ ability to concentrate CTCs from a large original blood volume to a smaller, highly concentrated volume enables a much greater blood volume to be interrogated by downstream isolation and characterization methods despite their low volume input limitations. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the effectiveness of different types of tasking on the measurement of peak slow phase velocity (SPV) for caloric testing and rotary chair testing. Method: This study evaluated the peak SPV response for caloric testing and rotary chair across five conditions. Three verbal, one tactile, and one condition without tasking were used for both caloric testing and rotary chair. The subjects consisted of 20 young adults (age range: 22--33 years, M = 26.65, SD = 3.72; seven male, 13 female) with normal vestibular function and no history of ear surgery or vestibular disorder. Study participation consisted of two visits with 24 hr minimum between each, one for caloric testing and one for rotary chair testing. The test completed at each visit was counterbalanced. Caloric Testing: The caloric irrigations were performed 5 times, with the ears randomized and tasking conditions randomized. Rotary Chair Testing: Rotary chair sinusoidal harmonic acceleration testing was performed 5 times at 0.08 Hz with the tasking conditions randomized. Results: Tasking of any kind resulted in significantly larger peak SPV responses when compared to the no tasking condition for rotary chair testing. When comparing each type of tasking, no significant differences were noted. No significant difference was noted when comparing the conditions with tasking to the no tasking condition for caloric testing. Conclusions: Clinically, either mental or tactile tasking can be utilized as a method to reduce VOR suppression during rotary chair testing. As no difference was found when comparing different verbal tasks to each other, the type of tasking can be catered to the patient. If verbal tasking cannot be completed, the braiding tactile task is a valid substitution. Caloric results varied widely across subjects and did not reach statistical significance, so conclusions on the need for tasking cannot be drawn. [ABSTRACT FROM AUTHOR]

During malignant transformation and cancer progression, tumor cells face both intrinsic and extrinsic stress, endoplasmic reticulum (ER) stress in particular. To survive and proliferate, tumor cells use multiple stress response pathways to mitigate ER stress, promoting disease aggression and treatment resistance. Among the stress response pathways is ER-associated degradation (ERAD), which consists of multiple components and steps working together to ensure protein quality and quantity. In addition to its established role in stress responses and tumor cell survival, ERAD has recently been shown to regulate tumor immunity. Here we summarize current knowledge on how ERAD promotes protein degradation, regulates immune cell development and function, participates in antigen presentation, exerts paradoxical roles on tumorigenesis and immunity, and thus impacts current cancer therapy. Collectively, ERAD is a critical protein homeostasis pathway intertwined with cancer development and tumor immunity. Of particular importance is the need to further unveil ERAD's enigmatic roles in tumor immunity to develop effective targeted and combination therapy for successful treatment of cancer. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this project was to explore the association between the perception of motion during caloric testing and two tasks associated with central vestibular processing: postural stability and visuospatial memory. Method: This was a prospective study of 25 patients who were found to have nonvestibular etiologies of their symptoms and normal vestibular function test results and who underwent caloric testing with a mean maximum slow phase eye velocity for each irrigation of 15° or greater. Following each caloric irrigation, patients were asked whether they had any sensation of movement. Patients were grouped based on the presence or absence of motion during the caloric exam (motion perception vs. absent perception). Postural stability was assessed using computerized dynamic posturography, and visuospatial memory was assessed using a memory match card game application. Results: There were no significant differences between groups on any measures of peripheral vestibular function. However, the Absent Perception Group showed greater postural instability during Condition 5 of posturography and performed significantly worse on a task of visuospatial working memory. Both age and absence of motion perception predicted abnormal performance on measures of postural stability and visuospatial working memory. Conclusions: There appears to be clinical implications to a lack of motion perception during the caloric exam in patients with an otherwise normal peripheral vestibular system. Based on the current findings, we are unable to determine whether differences in postural stability and visuospatial memory were due to age or a central vestibular processing deficit. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this study were (a) to investigate the optimal tone burst duration when recording the cervical vestibular evoked myogenic potential (cVEMP) and the ocular vestibular evoked myogenic potential (oVEMP) and (b) to determine whether monopolar recording influences the latency or amplitude of the cVEMP or the oVEMP. Method: Fifteen subjects (M =27.7years, SD =6.73years) participated in this study. The participants had no prior history of otological or neurological disease. Both oVEMPs and cVEMPs were recorded at a fixed stimulus level for stimulus durations of 2, 5, 10, and 25 ms. For both cVEMP and oVEMP, responses were obtained using a traditional differential recording montage and a monopolar recording montage. Results: The cVEMP and the oVEMP had the greatest amplitude in the 2-ms stimulus condition. There was a statistically significant decrease in amplitude for durations greater than 2 ms. Monopolar and bipolar cVEMP and oVEMP latencies and amplitudes were not significantly different. Conclusion: As stimulus duration increased beyond 2 ms, the amplitude of the response decreased for both the cVEMP and the oVEMP. There was no significant change in latency with increasing stimulus duration for either response. These results suggested the optimal stimulus duration for both the oVEMP and cVEMP is 2 ms, and there is no apparent advantage of using a bipolar recording technique. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is the most common cause of blindness for individuals age 50 and above in the developed world. Abnormal growth of choroidal blood vessels, or choroidal neovascularization (CNV), is a hallmark of the neovascular (wet) form of advanced AMD and leads to significant vision loss. A growing body of evidence supports a strong link between neovascular disease and inflammation. Metabolites of long-chain polyunsaturated fatty acids derived from the cytochrome P450 (CYP) monooxygenase pathway serve as vital second messengers that regulate a number of hormones and growth factors involved in inflammation and vascular function. Using transgenic mice with altered CYP lipid biosynthetic pathways in a mouse model of laser-induced CNV, we characterized the role of these lipid metabolites in regulating neovascular disease. We discovered that the CYP-derived lipid metabolites epoxydocosapentaenoic acids (EDPs) and epoxyeicosatetraenoic acids (EEQs) are vital in dampening CNV severity. Specifically, overexpression of the monooxygenase CYP2C8 or genetic ablation or inhibition of the soluble epoxide hydrolase (sEH) enzyme led to increased levels of EDP and EEQ with attenuated CNV development. In contrast, when we promoted the degradation of these CYP-derived metabolites by transgenic overexpression of sEH, the protective effect against CNV was lost. We found that these molecules work in part through their ability to regulate the expression of key leukocyte adhesion molecules, on both leukocytes and endothelial cells, thereby mediating leukocyte recruitment. These results suggest that CYP lipid signaling molecules and their regulators are potential therapeutic targets in neovascular diseases. [ABSTRACT FROM AUTHOR]

Proliferative retinopathic diseases often progress in 2 phases: initial regression of retinal vasculature (phase 1) followed by subsequent neovascularization (NV) (phase 2). The immune system has been shown to aid in vascular pruning in such retinopathies; however, little is known about the role of the alternative complement pathway in the initial vascular regression phase. Using a mouse model of oxygen-induced retinopathy (OIR), we observed that alternative complement pathway-deficient mice (Fb-/-) exhibited a mild decrease in vascular loss at postnatal day (P)8 compared with age- and strain-matched controls (P = 0.035). Laser capture microdissection was used to isolate the retinal blood vessels. Expression of the complement inhibitors Cd55 and Cd59 was significantly decreased in blood vessels isolated from hyperoxic retinas compared with those from normoxic control mice. Vegf expression was measured at P8 and found to be significantly lower in OIR mice than in normoxic control mice (P = 0.0048). Further examination of specific Vegf isoform expression revealed a significant decrease in Vegf120 (P = 0.00032) and Vegf188 (P = 0.0092). In conjunction with the major modulating effects of Vegf during early retinal vascular development, our data suggest a modest involvement of the alternative complement pathway in targeting vessels for regression in the initial vaso-obliteration stage of OIR. [ABSTRACT FROM AUTHOR]

The article offers information on a study concerning the development of new treatment strategies for the treatment of retinal detachment (RD). Topics discussed include impact of degeneration of photoreceptors on a number of retinal diseases; analysis of innate immune system regulators in the vitreous of human patients with RD; and effects of retinal hypoxia on alternative pathway activation and cell death in RD.

Background: Vision loss due to vascular disease of the retina is a leading cause of blindness in the world. Retinal angiomatous proliferation (RAP) is a subgroup of neovascular age-related macular degeneration (AMD), whereby abnormal blood vessels develop in the retina leading to debilitating vision loss and eventual blindness. The novel mouse strain, neoretinal vascularization 2 (NRV2), shows spontaneous fundus changes associated with abnormal neovascularization. The purpose of this study is to characterize the induction of pathologic angiogenesis in this mouse model. Methods: The NRV2 mice were examined from postnatal day 12 (p12) to 3 months. The phenotypic changes within the retina were evaluated by fundus photography, fluorescein angiography, optical coherence tomography, and immunohistochemical and electron microscopic analysis. The pathological neovascularization was imaged by confocal microscopy and reconstructed using three-dimensional image analysis software. Results: We found that NRV2 mice develop multifocal retinal depigmentation in the posterior fundus. Depigmented lesions developed vascular leakage observed by fluorescein angiography. The spontaneous angiogenesis arose from the retinal vascular plexus at postnatal day (p)15 and extended toward retinal pigment epithelium (RPE). By three months of age, histological analysis revealed encapsulation of the neovascular lesion by the RPE in the photoreceptor cell layer and subretinal space. Conclusions: The NRV2 mouse strain develops early neovascular lesions within the retina, which grow downward towards the RPE beginning at p15. This retinal neovascularization model mimics early stages of human retinal angiomatous proliferation (RAP) and will likely be a useful in elucidating targeted therapeutics for patients with ocular neovascular disease. [ABSTRACT FROM AUTHOR]

Background: One stimulus parameter not well established with respect to the ocular vestibular evoked myogenic potential (oVEMP) is stimulus polarity. Many research studies traditionally record oVEMPs using alternating polarity primarily. Purpose: The purpose of this study was to evaluate the effects of stimulus polarity on the oVEMP response under three different conditions (condensation, rarefaction, and alternating) with updated but established recording procedures-the belly-tendon electrode montage. Research Design: oVEMPs were assessed with changes in stimulus polarity in the seated upright position. Study Sample: Thirty otologically normal participants (60 ears) with no history of hearing or balance disorders and normal middle ear function. Data Collection and Analysis: Five hundred-hertz air-conducted tone bursts at 95-dB nHL were used to evoke the oVEMP response while recordings were made from the contralateral eye to acoustical stimulation using the belly-tendon electrode montage. Measurements were made using three polarities: alternating, condensation, and rarefaction. Natus Bio-logic AEP hardware and software was used for all data collection and analysis. Results: Condensation stimulus phase provided the largest response amplitude compared with alternating and/or rarefaction. Rarefaction provided the earliest latency among stimulus polarities. Conclusions: Condensation is a more effective stimulus polarity regarding response amplitude when recording the oVEMP. This study further supports the use of the belly-tendon electrode montage for recording the oVEMP response. [ABSTRACT FROM AUTHOR]

Solid tumors, especially those with aberrant MYCN activation, often harbor an immunosuppressive microenvironment to fuel malignant growth and trigger treatment resistance. Despite this knowledge, there are no effective strategies to tackle this problem. We found that chemokine-like factor ( CKLF ) is highly expressed by various solid tumor cells and transcriptionally up-regulated by MYCN. Using the MYCN-driven high-risk neuroblastoma as a model system, we demonstrated that as early as the premalignant stage, tumor cells secrete CKLF to attract CCR4-expressing CD4 + cells, inducing immunosuppression and tumor aggression. Genetic depletion of CD4 + T regulatory cells abolishes the immunorestrictive and protumorigenic effects of CKLF. Our work supports that disrupting CKLF-mediated cross-talk between tumor and CD4 + suppressor cells represents a promising immunotherapeutic approach to battling MYCN-driven tumors.

Phenotype-based screening of a fungal extract library yielded an active sample from a Penicillium sp. isolate that impaired zebrafish motility. Bioassay-guided purification led to the identification of 14 meroterpenoids including six new metabolites, arisugacins L-Q ( 4 , 5 , 8 , and 12 - 14 ), seven known arisugacins ( 1 - 3 , 6 , 7 , 9 , and 10 ), and one known terreulactone ( 11 ). Their structures were determined using a combination of NMR and HRESIMS data, evidence secured from theoretical and experimental ECD spectra, and the modified Mosher's method. The purified compounds were tested in zebrafish embryos, as well as in vitro for cholinesterase inhibition activities. Compound 12 produced defects in myotome structure (metameric muscle, which is critical for locomotion) in vivo and showed the most potent and selective acetylcholinesterase inhibitory activity with an IC 50 of 191 nM in vitro. The phenotype assay was also used to reveal bioactivities for several previously reported arisugacins, which had failed to show activity in prior cell-based and in vitro testing. This study demonstrates that utilization of the zebrafish phenotype assay is an effective approach for the identification of bioactive extracts, is compatible with the bioassay-guided compound purification strategies, and offers a valuable tool for probing complex natural product sources to detect bioactive small molecules with potential therapeutic or other commercial applications.