The multi-channel cochlear implant: Multi-disciplinary development of electrical stimulation of the cochlea and the resulting clinical benefit

AbstractThis multi-disciplinary research showed sound could be coded by electrical stimulation of the cochlea and peripheral auditory nervous system. But the temporal coding of frequency as seen in the experimental animal, was inadequate for the important speech frequencies. The data indicated the limitation was due in particular to deterministic firing of neurons and failure to reproduce the normal fine temporo-spatial pattern of neural responses seen with sound. However, the data also showed the need for the place coding of frequency, and this meant multi-electrodes inserted into the cochlea. Nevertheless, before this was evaluated on people we undertook biological safety studies to determine the effects of surgical trauma and electrical stimuli, and how to prevent infection. Then our research demonstrated place of stimulation had timbre and was perceived as vowels. This led to our discovery in 1978 of the formant-extraction speech code that first enabled severely-profoundly deaf people to understand running speech. This result in people who had hearing before becoming severely deaf was an outcome not previously considered possible. In 1985 it was the first multi-channel implant to be approved by the US Food and Drug Administration (FDA). It was also the fore runner of our advanced formant and fixed filter strategies When these codes were used from 1985 for those born deaf or deafened early in life we discovered there was a critical period when brain plasticity would allow speech perception and language to be developed near- normally, and this required in particular the acquisition of place coding. In 1990 this led to the first cochlear implant to be approved by the FDA for use in children. Finally, we achieved binaural hearing in 1989 with bilateral cochlear implants, followed by bimodal speech processing in 1990 with a hearing aid in one ear and implant in the other. The above research has been developed industrially, with for example 250,000 people worldwide receiving the Cochlear device in 2013, and as of December 2012 the NIH estimated that approximately 324,200 people worldwide had received this and other implants (NIH Publication No. 11-4798).This article is part of a Special Issue entitled <Lasker Award>

Alvar Aalto, el maestro de la modernidad renovada

4. Alvar Aalto, el maestro de la modernidad renovada 4. 1. La obra aaltiana después de clasicismo nórdico y hasta la biblioteca de Viipuri 4. l. l. Composición por partes, linealidad y diversidad de relación entre forma y estructura 4. 1. 2. Forma y estructura en el periódico de Turku 4. l. 3. Complejidad del método en la biblioteca de Viipuri 4. 2. Los apriorismos formales como método de proyectar: la forma ondulada 4. 2. 1. La ondulación como forma apriorística: el pabellón de la Feria de Nueva York de 1939 4. 2. 2. El edificio ondulado 4. 2. 3. La ciudad ondulada 4. 3. La forma de abanico como forma apriorística 4. 3. 1. La concepción del espacio y su complejidad: Otaniemi 4. 3. 2. La forma de abanico y la configuración del espacio en las bibliotecas de los años sesenta 4. 3. 3. La forma de abanico en la configuración del plano: las torres de apartamentos 4. 4. Forma ilusoria e inspiración figurativa 4. 5. Una ilusión vernácula: villa Mairea 4. 6. Ideas tradicionales y composición urbana 4. 6. 1. La síntesis entre tradición y modernidad en el Ayuntamiento de Saynatsalo 4. 6. 2. Composición plana como lenguaje de la complejidad volumétrica en el Instituto de Pensiones de Helsinki 4. 6. 3. Un palacio moderno para el centro de Helsinld: el edificio Enso Gutzeit. Otros edificios urbanos 4. 7. Arquitectura moderna para una ciudad ideal: el centro de Seinajoki 4. 8. La complejidad de la forma y del espacio y su control. Iglesias y auditorios 4. 8. 1. Variaciones basilicales y complejidad extrema en las iglesias 4. 8. 2. Espacio y conjunto: la casa de la Cultura y el palacio de Congresos de Helsinld 4. 8. 3. Complejidad unitaria en la Ópera de Essen 4. 9. Un antecedente aaltiano y un discípulo: Erik Bryggman y Reima Pietil

Generalized AdS/CFT Dualities and Space-Time Symmetries of M/Superstring Theory

I review the relationship between AdS/CFT (anti-de Sitter / conformal field theory) dualities and the general theory of unitary lowest weight (ULWR) (positive energy) representations of non-compact space-time groups and supergroups. The ULWR's have the remarkable property that they can be constructed by tensoring some fundamental ULWR's (singletons or doubletons). Furthermore, one can go from the manifestly unitary compact basis of the ULWR's of the conformal group (Wigner picture) to the manifestly covariant coherent state basis (Dirac picture) labelled by the space-time coordinates. Hence every irreducible ULWR corresponds to a covariant field with a definite conformal dimension. These results extend to higher dimensional generalized spacetimes (superspaces) defined by Jordan (super) algebras and Jordan (super) triple systems. In particular, they extend to the ULWR's of the M-theory symmetry superalgebra OSp(1/32,R).Comment: Latex file, 11 pages; invited talk to appear in the Proceedings of the IXth Marcel Grossmann Meeting (Rome, July 2000

In vitro growth and differentiation of primary myoblasts on thiophene based conducting polymers

Polythiophenes are attractive candidate polymers for use in synthetic cell scaffolds as they are amenable to modification of functional groups as a means by which to increase biocompatibility. In the current study we analysed the physical properties and response of primary myoblasts to three thiophene polymers synthesized from either a basic bithiophene monomer or from one of two different thiophene monomers with alkoxy functional groups. In addition, the effect of the dopants pTS- and ClO4 - was investigated. In general, it was found that pTS- doped polymers were significantly smoother and tended to be more hydrophilic than their ClO 4 - doped counterparts, demonstrating that the choice of dopant significantly affects the polythiophene physical properties. These properties had a significant effect on the response of primary myoblasts to the polymer surfaces; LDH activity measured from cells harvested at 24 and 48 h post-seeding revealed significant differences between numbers of cells attaching to the different thiophene polymers, whilst all of the polymers equally supported cell doubling over the 48 h period. Differences in morphology were also observed, with reduced cell spreading observed on polymers with alkoxy groups. In addition, significant differences were seen in the polymers\u27 ability to support myoblast fusion. In general pTS- doped polymers were better able to support fusion than their ClO4 - doped counterparts. These studies demonstrate that modification of thiophene polymers can be used to promote specific cellular response (e.g. proliferation over differentiation) without the use of biological agents. 2013 The Royal Society of Chemistry

Invasion Expansion: Time since introduction best predicts global ranges of marine invaders.

Strategies for managing biological invasions are often based on the premise that characteristics of invading species and the invaded environment are key predictors of the invader's distribution. Yet, for either biological traits or environmental characteristics to explain distribution, adequate time must have elapsed for species to spread to all potential habitats. We compiled and analyzed a database of natural history and ecological traits of 138 coastal marine invertebrate species, the environmental conditions at sites to which they have been introduced, and their date of first introduction. We found that time since introduction explained the largest fraction (20%) of the variability in non-native range size, while traits of the species and environmental variables had significant, but minimal, influence on non-native range size. The positive relationship between time since introduction and range size indicates that non-native marine invertebrate species are not at equilibrium and are still spreading, posing a major challenge for management of coastal ecosystems

Spatial variation in microbial communities associated with sea-ice algae in Commonwealth Bay, East Antarctica

Antarctic sea-ice forms a complex and dynamic system that drives many ecological processes in the Southern Ocean. Sea-ice microalgae and their associated microbial communities are understood to influence nutrient flow and allocation in marine polar environments. Sea-ice microalgae and their microbiota can have high seasonal and regional (>1000 km2) compositional and abundance variation, driven by factors modulating their growth, symbiotic interactions and function. In contrast, our knowledge of small-scale variation in these communities is limited. Understanding variation across multiple scales and its potential drivers is critical for informing on how multiple stressors impact sea-ice communities and the functions they provide. Here, we characterized bacterial communities associated with sea-ice microalgae and the potential drivers that influence their variation across a range of spatial scales (metres to >10 kms) in a previously understudied area in Commonwealth Bay, East Antarctica where anomalous events have substantially and rapidly expanded local sea-ice coverage. We found a higher abundance and different composition of bacterial communities living in sea-ice microalgae closer to the shore compared to those further from the coast. Variation in community structure increased linearly with distance between samples. Ice thickness and depth to the seabed were found to be poor predictors of these communities. Further research on the small-scale environmental drivers influencing these communities is needed to fully understand how large-scale regional events can affect local function and ecosystem processes

Regulation of immune responses in primary biliary cholangitis: a transcriptomic analysis of peripheral immune cells

BACKGROUND AIMS: In patients with primary biliary cholangitis (PBC), the serum liver biochemistry measured during treatment with ursodeoxycholic acid-the UDCA response-accurately predicts long-term outcome. Molecular characterization of patients stratified by UDCA response can improve biological understanding of the high-risk disease, thereby helping to identify alternative approaches to disease-modifying therapy. In this study, we sought to characterize the immunobiology of the UDCA response using transcriptional profiling of peripheral blood mononuclear cell subsets. METHODS: We performed bulk RNA-sequencing of monocytes and TH1, TH17, TREG, and B cells isolated from the peripheral blood of 15 PBC patients with adequate UDCA response ("responders"), 16 PBC patients with inadequate UDCA response ("nonresponders"), and 15 matched controls. We used the Weighted Gene Co-expression Network Analysis to identify networks of co-expressed genes ("modules") associated with response status and the most highly connected genes ("hub genes") within them. Finally, we performed a Multi-Omics Factor Analysis of the Weighted Gene Co-expression Network Analysis modules to identify the principal axes of biological variation ("latent factors") across all peripheral blood mononuclear cell subsets. RESULTS: Using the Weighted Gene Co-expression Network Analysis, we identified modules associated with response and/or disease status (q<0.05) in each peripheral blood mononuclear cell subset. Hub genes and functional annotations suggested that monocytes are proinflammatory in nonresponders, but antiinflammatory in responders; TH1 and TH17 cells are activated in all PBC cases but better regulated in responders; and TREG cells are activated-but also kept in check-in responders. Using the Multi-Omics Factor Analysis, we found that antiinflammatory activity in monocytes, regulation of TH1 cells, and activation of TREG cells are interrelated and more prominent in responders. CONCLUSIONS: We provide evidence that adaptive immune responses are better regulated in patients with PBC with adequate UDCA response

Shockwave lithotripsy compared with ureteroscopic stone treatment for adults with ureteric stones : the TISU non-inferiority RCT

Acknowledgements The authors wish to thank the patients who participated in the TISU trial.We also thank Stanley Coutts (patient representative) and Charles Clark (patient representative and co-applicant) for their contribution to the design of the participant-facing documents (patient information sheet and questionnaires); Sharon Wren for her secretarial support and data management; previous data co-ordinators, Jessica Wood and Margery Heath, for their data and trial management support; the CHaRT programming team led by Gladys McPherson (to 2016) and Mark Forrest (2016–present); other staff within CHaRT and the HSRU for their assistance with the trial (Cynthia Fraser); members of the PMG for their ongoing advice and support of the trial, plus the independent members of the TSC and DMC; and the staff at the recruitment sites who facilitated the recruitment, treatment and follow-up of trial participants (all listed below); and, finally, we would like to thank the National Institute for Health Research and the Health Technology Assessment programme for funding the TISU trial. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 19. See the NIHR Journals Library website for further project information.Peer reviewedPublisher PD

Metamictization of zircon: Raman spectroscopic study

Raman spectroscopy of radiation-damaged natural zircon samples shows increased line broadening and shifts of phonon frequencies with increasing radiation dose. Stretching and bending frequencies of SiO4 tetrahedra soften dramatically with increasing radiation damage. The frequency shifts can be used to determine the degree of radiation damage. Broad spectral bands related to Si-O stretching vibrations between 900 and 1000 cm-1 were observed in metamict/amorphous zircon. The radiation-dose-independent spectral profiles and the coexistence of this broad background and relative sharp Raman modes in partially damaged samples indicate that these bands are correlated with amorphous domains in zircon. The spectral profiles of metamict zircon suggest that in comparison with silica, the SiO4 tetrahedra are less polymerized in metamict zircon. This study also shows that ZrO2 and SiO2 are not the principal products of metamictization in zircon. No indication of bulk chemical unmixing of zircon into ZrO2 and SiO2 was found in 26 samples with a large variation of radiation damage (maximum dose: 23.5 × 1018 -events g-1 ). Only one sample showed clearly, in all measured sample areas, extra sharp lines at 146, 260, 312, 460 and 642 cm-1 characteristic of tetragonal ZrO2 . The geological (and possibly artificial heating) history of this sample is not known. It is concluded that radiation damage without subsequent high temperature annealing does not cause unmixing of zircon into constituent oxides.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48886/2/c00833.pd

Tropical forcing of increased Southern Ocean climate variability revealed by a 140-year subantarctic temperate reconstruction

Occupying 14% of the world’s surface, the Southern Ocean plays a fundamental role in global climate, ocean circulation, carbon cycling and Antarctic ice-sheet stability. Unfortunately, high interannual variability and a dearth of instrumental observations before the 1950s limits our understanding of how marine-atmosphere-ice domains interact on multi-decadal timescales and the impact of anthropogenic forcing. Here we integrate climate-sensitive tree growth with ocean and atmospheric observations on southwest Pacific subantarctic islands that lie at the boundary of polar and subtropical climates (52–54˚S). Our annually-resolved temperature reconstruction captures regional change since the 1870s and demonstrates a significant increase in variability from the mid-twentieth century, a phenomenon predating the observational record. Climate reanalysis and modelling shows a parallel change in tropical Pacific sea surface temperatures that generate an atmospheric Rossby wave train which propagates across a large part of the Southern Hemisphere during the austral spring and summer