Physiome-on-a-Chip: The Challenge of “Scaling” in Design, Operation, and Translation of Microphysiological Systems

Scaling of a microphysiological system (MPS) or physiome-on-a-chip is arguably two interrelated, modeling-based activities: on-platform scaling and in vitro-in vivo translation. This dual approach reduces the need to perfectly rescale and mimic in vivo physiology, an aspiration that is both extremely challenging and not substantively meaningful because of uncertain relevance of any specific physiological condition. Accordingly, this perspective offers a tractable approach for designing interacting MPSs and relating in vitro results to analogous context in vivo.United States. Defense Advanced Research Projects Agency. Microphysiological Systems Program (Grant W911NF-12-2-0039)National Institutes of Health (U.S.) Microphysiological Systems Program (Grant 4-UH3-TR000496-03)United States. Army Research Office (Institute for Collaborative Biotechnologies. Grant W911NF-09- 0001

Access Anglesey 2018: Lessons from an inclusive field course

Abstract. Traditional methods of fieldwork delivery can present learners with a range of physical, cognitive and social challenges which may subsequently hinder their ability to engage effectively with learning. We developed a residential geoscience field course designed to be physically accessible to, and socially inclusive of, a diverse range of learners including those with limited physical mobility and neurodiverse conditions. This paper presents the logistical and pedagogical challenges involved in delivering such a field course. In terms of pedagogic design scheduling, pace and timing, and the ability to access content in multiple ways were critical to ensuring that all students were included in the learning. The most effective mitigations were the simplest and benefitted the whole group. Practical interventions found to support access and inclusion for the benefit of all participants included using an audio tour-guide system to communicate with students at field locations, using a four-wheel drive vehicle to improve access to specific locations, providing alternative exercises such as prepared photomicrographs and rock specimens, providing electronic tablets with suitable apps, and selecting accommodation with accessible common-room spaces, and a dedicated quiet room. </jats:p

Achieving Inclusive Field-based Education: Results and Recommendations from an Accessible Geoscience Field Trip

Learners with disabilities are often denied field-based learning experiences in naturalistic disciplines. Geology can present substantial barriers due to rugged terrain in difficult-to-reach locations. In 2014, a field trip was executed with the dual purpose of 1) designing inclusion in field learning and 2) demonstrating to college faculty an accessible field experience. Direct observations of participants on the trip, as well as pre- and post-trip focus groups, illuminate the student and faculty field learning experience. Geoscience faculty have little guidance or support in understanding what disability is, how to reconcile accommodation with field-geology learning goals, and they cited instances where disability service providers acted as gatekeepers. The net effect of these ontologies is to reduce faculty empathy with, and thus their ability to be inclusive of, students with disabilities in field settings. Recommendations for teachers include taking campus disability-services administrators on field trips, opening and maintaining communications with disability service providers, and designing pedagogically sound field trips that align as much as possible to principles of universal design. An advocacy approach is described, which focuses on the students and the educational process, instead of on institutional compliance. Finally, geoscience faculty should conceptualize disability service providers as accessibility service providers

Differential wedging of vertebral body and intervertebral disc in thoracic and lumbar spine in adolescent idiopathic scoliosis – A cross sectional study in 150 patients

<p>Abstract</p> <p>Background</p> <p>Hueter-Volkmann's law regarding growth modulation suggests that increased pressure on the end plate of bone retards the growth (Hueter) and conversely, reduced pressure accelerates the growth (Volkmann). Literature described the same principle in Rat-tail model. Human spine and its deformity i.e. scoliosis has also same kind of pattern during the growth period which causes wedging in disc or vertebral body.</p> <p>Methods</p> <p>This cross sectional study in 150 patients of adolescent idiopathic scoliosis was done to evaluate vertebral body and disc wedging in scoliosis and to compare the extent of differential wedging of body and disc, in thoracic and lumbar area. We measured wedging of vertebral bodies and discs, along with two adjacent vertebrae and disc, above and below the apex and evaluated them according to severity of curve (curve < 30° and curve > 30°) to find the relationship of vertebral body or disc wedging with scoliosis in thoracic and lumbar spine. We also compared the wedging and rotations of vertebrae.</p> <p>Results</p> <p>In both thoracic and lumbar curves, we found that greater the degree of scoliosis, greater the wedging in both disc and body and the degree of wedging was more at apex supporting the theory of growth retardation in stress concentration area. However, the degree of wedging in vertebral body is more than the disc in thoracic spine while the wedging was more in disc than body in lumbar spine. On comparing the wedging with the rotation, we did not find any significant relationship suggesting that it has no relation with rotation.</p> <p>Conclusion</p> <p>From our study, we can conclude that wedging in disc and body are increasing with progression on scoliosis and maximum at apex; however there is differential wedging of body and disc, in thoracic and lumbar area, that is vertebral body wedging is more profound in thoracic area while disc wedging is more profound in lumbar area which possibly form 'vicious cycle' by asymmetric loading to spine for the progression of curve.</p

Motivational interviewing for low mood and adjustment early after stroke: a feasibility randomised trial

Background Management of psychological adjustment and low mood after stroke can result in positive health outcomes. We have adapted a talk-based therapy, motivational interviewing (MI), and shown it to be potentially effective for managing low mood and supporting psychological adjustment post-stroke in a single-centre trial. In the current study, we aimed to explore the feasibility of delivering MI using clinical stroke team members, and using an attention control (AC), to inform the protocol for a future definitive trial. Methods This parallel two-arm feasibility trial took place in north-west England. Recruitment occurred between December 2012 and November 2013. Participants were stroke patients aged 18 years or over, who were medically stable, had no severe communication problems, and were residents of the hospital catchment. Randomisation was to MI or AC, and was conducted by a researcher not involved in recruitment using opaque sealed envelopes. The main outcome measures were descriptions of study feasibility (recruitment/retention rates, MI delivery by clinical staff, use of AC) and acceptability (through qualitative interviews and completion of study measures), and fidelity to MI and AC (through review of session audio-recordings). Information was also collected on participants’ mood, quality of life, adjustment, and resource-use. Results Over 12 months, 461 patients were screened, 124 were screened eligible, and 49 were randomised: 23 to MI, 26 to AC. At 3 months, 13 MI and 18 AC participants completed the follow-up assessment (63% retention). This was less than expected based on our original trial. An AC was successfully implemented. Alternative approaches would be required to ensure the feasibility of clinical staff delivering MI. The study measures, MI, and AC interventions were considered acceptable, and there was good fidelity to the interventions. There were no adverse events related to study participation. Conclusions It was possible to recruit and retain participants, train clinical staff to deliver MI, and implement an appropriate AC. Changes would be necessary to conduct a future multi-centre trial, including: assuming a recruitment rate lower than that in the current study; implementing more strategies to increase participant retention; and considering alternative clinical staff groups to undertake the delivery of MI and AC

To respond or not to respond - a personal perspective of intestinal tolerance

For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research

Measurement of vertebral rotation in adolescent idiopathic scoliosis with low-dose CT in prone position - method description and reliability analysis

<p>Abstract</p> <p>Background</p> <p>To our knowledge there is no report in the literature on measurements of vertebral rotation with low-dose computed tomography (CT) in prone position.</p> <p>Aims</p> <p>To describe and test the reliability of this new method, compare it with other methods in use and evaluate the influence of body position on the degree of vertebral rotation measured by different radiological methods.</p> <p>Study design</p> <p>Retrospective study.</p> <p>Methods</p> <p>25 consecutive patients with adolescent idiopathic scoliosis scheduled for surgery (17 girls, 8 boys) aged 15 ± 2 years (mean ± SD) were included in the analysis of this study. The degree of the vertebral rotation was in all patients measured according to the method of Perdriolle on standing plain radiographs and on supine CT scanogram, and according to the method of Aaro and Dahlborn on axial CT images in prone position and on magnetic resonance imaging (MRI) in supine position. The measurements were done by one neuroradiologist at two different occasions. Bland and Altman statistical approach was used in the reliability assessment.</p> <p>Results</p> <p>The reliability of measuring vertebral rotation by axial CT images in prone position was almost perfect with an intraclass correlation coefficient of 0.95, a random error of the intraobserver differences of 2.3°, a repeatability coefficient of 3.2° and a coefficient of variation of 18.4%. Corresponding values for measurements on CT scanogram were 0.83, 5.1°, 7.2°, and 32.8%, respectively, indicating lower reliability of the latter modality and method. The degree of vertebral rotation measured on standing plain radiographs, prone CT scanogram, axial images on CT in prone position and on MRI in supine position were 25.7 ± 9.8°, 21.9 ± 8.3°, 17.4 ± 7.1°, and 16.1 ± 6.5°, respectively. The vertebral rotation measured on axial CT images in prone position was in average 7.5% larger than that measured on axial MRI in supine position.</p> <p>Conclusions</p> <p>This study has shown that measurements of vertebral rotation in prone position were more reliable on axial CT images than on CT scanogram. The measurement of vertebral rotation on CT (corrected to the pelvic tilt) in prone position imposes lower impact of the recumbent position on the vertebral rotation than did MRI in supine position. However, the magnitude of differences is of doubtful clinical significance.</p

A new method for measuring torsional deformity in scoliosis

<p>Abstract</p> <p>Background</p> <p>The importance of spinal rotational and torsional deformity in the etiology and the management of scoliosis are well-recognized. For measuring the posterior spinal component rotation, Ho's method was reported to be reliable. However, there is no practical method to measure the anterior spinal component rotation. Moreover, there is also no method to quantify the spinal torsional deformity in scoliosis. The goal of this study is to characterize scoliosis and its deformity to hypothesize the etiology and the development of scoliosis, and to establish a new method for the measurement of the vertebral body rotation and spinal torsional deformity in scoliosis using CT scans.</p> <p>Methods</p> <p>Pre-operative CT scans of 25 non-congenital scoliosis patients were recruited and the apical vertebral rotation was measured by a newly developed method and Ho's method. Ho's method adopts the laminae as the rotational landmark. For a new method to measure the apical vertebral rotation, the posterior point just beneath each pedicle was used as a landmark. For quantifying the spinal torsional deformity angle, the rotational angle difference between the two methods was calculated.</p> <p>Results</p> <p>Intraobserver and interobserver reliability analyses showed both methods to be reliable. Apical vertebral rotation revealed 13.9 ± 6.8 (mean ± standard deviation) degrees by the new method and 7.9 ± 6.3 by Ho's method. Right spinal rotation was assigned a positive value. The discrepancy of rotation (6.1 ± 3.9 degrees), meaning that the anterior component rotated more than the posterior component, was considered to express the spinal torsional deformity to the convex side.</p> <p>Conclusions</p> <p>We have developed an easy, reliable and practical method to measure the rotation of the spinal anterior component using a CT scan. Furthermore, we quantified the spinal torsional deformity to the convex side in scoliosis by comparing the rotation between the anterior and posterior components.</p

Contrasting Transcriptional Responses of a Virulent and an Attenuated Strain of Mycobacterium tuberculosis Infecting Macrophages

Along with the recent identification of single nucleotide polymorphisms in H37Ra when compared to H37Rv, our demonstration of differential expression of PhoP-regulated and ESX-1 region-related genes during macrophage infection further highlights the significance of these genes in the attenuation of H37Ra