Steady streaming as a method for drug delivery to the inner ear

Sensorineural hearing damage occurs when the hair cells which transduce mechanical input to electrical become damaged in the cochlea. Current drug therapies, whilst being promising in their ability to heal these cells, are limited by the inability to reliably administer them to their target sites. This work looks at the phenomenon of steady streaming, a non-zero net motion in a fluctuating flow with non-conservative body forces, and investigates whether or not it is possible to harness the effect in order to deliver and potentially even specifically target damaged hair cells in the cochlea. Using the WKB model for the basilar membrane waves alongside experimental data to a create computational fluid dynamic simulation of the guinea pig cochlea, particle tracking was undertaken in order to find individual particle trajectories in the flows under pure tone, pitch change and multiple pitch stimulation. The steady streaming velocities and relative efficacy of the different stimuli were then determined and multiple frequency stimulation found to be superior as a method of drug transportation due to the setup of a so-called `streaming channel' along which particles flow.Open Acces

Ideology and identity: ‘knowing’ workers in early Soviet Russia, 1917-1921

The period 1917-1921 provides an insight not only into the policies of the new Soviet state but the mindset of its leaders. These four years were a time of intense political struggle and socio-economic disruption, which exposed the tension between ideology and practice in Bolshevik discourse and policy making. Workers, specifically metalworkers, were a focal point of Bolshevik ideology and policies in this period. This thesis will explore how the Soviet state conceptualised metalworkers, through ideology, and how this informed their engagement with workers, through policy. This will be done through an examination of state statistical data and how prominent state polices, cultural policy and treatment of dissent, and discourse changed over this period. It will also focus on a case study of Sormovo Metalworks, a suburb of Nizhnii Novgrorod, and use local sources to investigate how the tension between ideology and practice played out on a local level. It will explore how local Bolsheviks conceptualised and engaged with Sormovo workers and how this was shaped by three things: Bolshevik ideology, the context of the Civil War and the specific local conditions of Sormovo and its workforce. The Civil War period witnessed a change in the discourse and policies of the Soviet state, which became more coercive, interventionist and repressive as the war progressed. Sormovo Metalworks was a large metalworking complex in a largely rural province; it had a skilled workforce with a tradition of labour activism through striking and was dominated by the Socialist Revolutionary Party. The move towards an increasingly centralised state was utilised by local Bolsheviks in Sormovo in an attempt to end the labour activism of its workforce and crush political opposition. However, despite the increasingly assertive discourse about the identity of metalworkers and the state’s drive for economic, political and cultural centralisation, Sormovo workers had the ability to challenge, subvert and negotiate state labels and even policies. This case study reveals that although Sormovo workers suffered repeated challenges to their identity by the state, local government and the economic crises of the Civil War, they continued to utilise self-identification based on their skill and shared socio-economic experience. This in turn shaped their vertical and horizontal social, economic and political relationships with those around them. Although the central state became politically and economically centralised and authoritarian, the identity of the grassroots in Sormovo remained diverse and fluid

Developing a Web Analytics Strategy for the National Science Digital Library

In August 2004, a two-day workshop was held on Developing a Web Analytics Strategy for the National Science Digital Library (NSDL) . The workshop was sponsored by the NSDL Educational Impact and Evaluation Standing Committee (EIESC) and was jointly organized with the NSDL Technology Standing Committee (TSC). It brought together 26 representatives from government and industry, as well as some of the projects funded by the National Science Foundation (NSF) NSDL program, to discuss how web metrics could be implemented in a pilot study to identify current NSDL use and develop strategies to support the collection of usage data across NSDL in the future. This new pilot follows a study that the EIESC conducted in 2002 to identify and collect basic web metrics data for NSDL.A bibliography on web metrics was prepared and distributed to the participants of the 2004 workshop. During the workshop, participants first reviewed the processes and technology used to gather web metrics data by two different organizations: the Association of Research Libraries E-Metrics Project and Sun Microsystems. Through a series of breakout and plenary sessions, participants identified high-level goals for the new pilot study, formulated and prioritized a list of desired effects and requirements for collecting web metrics across NSDL, and developed recommendations for implementing web metrics data collection on a project and program level. The workshop concluded with the EIESC and TSC establishing a joint taskforce to lead the pilot study in NSDL over the next year. Web analytics will be used to address two high-level goals. That high quality learning resources be accessible to a large spectrum of the US population That there be value added to users and projects by participating in NSDL.This workshop report provides a brief history of previous evaluation activities across NSDL and discusses the importance of web analytics to NSDL. After a review of the literature on web metrics, the report identifies cross-cutting issues that affect implementing web metrics in the upcoming pilot study (e.g., build vs. buy, data ownership and storage, organizational structure that supports ongoing data collection, user privacy); describes the goals and requirements for the pilot study; and lists near term action items for the joint task force. Documents from the workshop, including a preliminary report entitled Workshop on Web Metrics in NSDL , slides from ARL and Sun Microsystems presentations, participant statements and the web metrics bibliography can be found on the workshop website

Cardiff Model Toolkit: Community Guidance For Violence Prevention

More than half of violent crime in the United States is not reported to law enforcement, according to the U.S. Department of Justice. That means cities and communities lack a complete understanding of where violence occurs, which limits the ability to develop successful solutions.The Cardiff Violence Prevention Model provides a way for communities to gain a clearer picture about where violence is occurring by combining and mapping both hospital and police data on violence.But more than just an approach to map and understand violence, the Cardiff Model provides a straightforward framework for hospitals, law enforcement agencies, public health agencies, community groups, and others interested in violence prevention to work together and develop collaborative violence prevention strategies

Exploring how children with reading difficulties respond to instructional supports in literacy games and the role of prior knowledge

Digital literacy games can be beneficial for children with reading difficulties as a supplement to classroom instruction and an important feature of these games are the instructional supports, such as feedback. To be effective, feedback needs to build on prior instruction and match a learner's level of prior knowledge. However, there is limited research around the relationship between prior knowledge, instruction and feedback in the context of learning games. This paper presents an empirical study exploring the influence of prior knowledge on response to feedback, in two conditions: with or without instruction. Thirty-six primary children (age 8–11) with reading difficulties participated: each child was assessed for their prior knowledge of two suffix types—noun and adjective suffixes. They subsequently received additional instruction for one suffix type and then played two rounds of a literacy game—one round for each suffix type. Our analysis shows that prior knowledge predicted initial success rates and performance after a verbal hint differently, depending on whether instruction was provided. These results are discussed with regards to learning game feedback design and the impact on different types of knowledge involved in gameplay, as well as other game design elements that might support knowledge building during gamepla

Appropriation of literacy technologies in the classroom: reflections from creative learning design workshops with primary school teachers

Background: Approaches to teacher professional development, such as learning designs (LDs), can facilitate primary school teachers' appropriation of literacy technology in the classroom. LDs are detailed learning activities and interventions designed by teachers to plan their use of technology. Methods: Using a creative design methodology to carry out a series of LD workshops with teachers, we aimed to understand how primary school teachers envision learning and teaching with two distinct technologies designed to support children's reading skills: a game and an e-reader. Employing systematic qualitative content analysis, we compared LDs developed by teachers for each technology. Results: Our study shows that while principles of teacher instruction are consistently incorporated across the LDs, the design of each technology plays an important role in how teachers plan their students' learning and focal reading skills. Further, teachers' perception of the technology is as important as the features of the design. Compared with the e-reader, the game is perceived as an individual practice activity with less opportunities to learn with peers. Finally, across both technologies, teachers envision supporting additional literacy skills, beyond those designed in the technology, highlighting the importance of explicitly facilitating LDs intended to foster within-subject learning. Conclusions: These findings raise a new set of considerations on how to support teachers to design literacy learning and teaching activities with technology, and also offer a new methodological approach to facilitate LDs in future research and teacher training

Collimation and asymmetry of the hot blast wave from the recurrent nova V745 Scorpii

The recurrent symbiotic nova V745 Sco exploded on 2014 February 6 and was observed on February 22 and 23 by the Chandra X-ray Observatory Transmission Grating Spectrometers. By that time the supersoft source phase had already ended and Chandra spectra are consistent with emission from a hot, shock-heated circumstellar medium with temperatures exceeding 10^7K. X-ray line profiles are more sharply peaked than expected for a spherically-symmetric blast wave, with a full width at zero intensity of approximately 2400 km/s, a full width at half maximum of 1200 +/- 30 km/s and an average net blueshift of 165 +/- 10 km/s. The red wings of lines are increasingly absorbed toward longer wavelengths by material within the remnant. We conclude that the blast wave was sculpted by an aspherical circumstellar medium in which an equatorial density enhancement plays a role, as in earlier symbiotic nova explosions. Expansion of the dominant X-ray emitting material is aligned close to the plane of the sky and most consistent with an orbit seen close to face-on. Comparison of an analytical blast wave model with the X-ray spectra, Swift observations and near-infrared line widths indicates the explosion energy was approximately 10^43 erg, and confirms an ejected mass of approximately 10^-7 Msun. The total mass lost is an order of magnitude lower than the accreted mass required to have initiated the explosion, indicating the white dwarf is gaining mass and is a supernova Type 1a progenitor candidate.Comment: To appear in the Astrophysical Journa

Enhancement of CD8(+) T-cell memory by removal of a vaccinia virus nuclear factor-κB inhibitor.

Factors influencing T-cell responses are important for vaccine development but are incompletely understood. Here, vaccinia virus (VACV) protein N1 is shown to impair the development of both effector and memory CD8(+) T cells and this correlates with its inhibition of nuclear factor-κB (NF-κB) activation. Infection with VACVs that either have the N1L gene deleted (vΔN1) or contain a I6E mutation (vN1.I6E) that abrogates its inhibition of NF-κB resulted in increased central and memory CD8(+) T-cell populations, increased CD8(+) T-cell cytotoxicity and lower virus titres after challenge. Furthermore, CD8(+) memory T-cell function was increased following infection with vN1.I6E, with more interferon-γ production and greater protection against VACV infection following passive transfer to naive mice, compared with CD8(+) T cells from mice infected with wild-type virus (vN1.WT). This demonstrates the importance of NF-κB activation within infected cells for long-term CD8(+) T-cell memory and vaccine efficacy. Further, it provides a rationale for deleting N1 from VACV vectors to enhance CD8(+) T-cell immunogenicity, while simultaneously reducing virulence to improve vaccine safety.This work was supported by grants from the Wellcome Trust and the Medical Research Council. GLS is a Wellcome Trust Principal Research Fellow.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/imm.1242