6,092 research outputs found

    Intraoperative electrocochleographic characteristics of auditory neuropathy spectrum disorder in cochlear implant subjects

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    Auditory neuropathy spectrum disorder (ANSD) is characterized by an apparent discrepancy between measures of cochlear and neural function based on auditory brainstem response (ABR) testing. Clinical indicators of ANSD are a present cochlear microphonic (CM) with small or absent wave V. Many identified ANSD patients have speech impairment severe enough that cochlear implantation (CI) is indicated. To better understand the cochleae identified with ANSD that lead to a CI, we performed intraoperative round window electrocochleography (ECochG) to tone bursts in children (n = 167) and adults (n = 163). Magnitudes of the responses to tones of different frequencies were summed to measure the “total response” (ECochG-TR), a metric often dominated by hair cell activity, and auditory nerve activity was estimated visually from the compound action potential (CAP) and auditory nerve neurophonic (ANN) as a ranked “Nerve Score”. Subjects identified as ANSD (45 ears in children, 3 in adults) had higher values of ECochG-TR than adult and pediatric subjects also receiving CIs not identified as ANSD. However, nerve scores of the ANSD group were similar to the other cohorts, although dominated by the ANN to low frequencies more than in the non-ANSD groups. To high frequencies, the common morphology of ANSD cases was a large CM and summating potential, and small or absent CAP. Common morphologies in other groups were either only a CM, or a combination of CM and CAP. These results indicate that responses to high frequencies, derived primarily from hair cells, are the main source of the CM used to evaluate ANSD in the clinical setting. However, the clinical tests do not capture the wide range of neural activity seen to low frequency sounds

    Altered patterns of gene duplication and differential gene gain and loss in fungal pathogens

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    <p>Abstract</p> <p>Background</p> <p>Duplication, followed by fixation or random loss of novel genes, contributes to genome evolution. Particular outcomes of duplication events are possibly associated with pathogenic life histories in fungi. To date, differential gene gain and loss have not been studied at genomic scales in fungal pathogens, despite this phenomenon's known importance in virulence in bacteria and viruses.</p> <p>Results</p> <p>To determine if patterns of gene duplication differed between pathogens and non-pathogens, we identified gene families across nine euascomycete and two basidiomycete species. Gene family size distributions were fit to power laws to compare gene duplication trends in pathogens <it>versus </it>non-pathogens. Fungal phytopathogens showed globally altered patterns of gene duplication, as indicated by differences in gene family size distribution. We also identified sixteen examples of gene family expansion and five instances of gene family contraction in pathogenic lineages. Expanded gene families included those predicted to be important in melanin biosynthesis, host cell wall degradation and transport functions. Contracted families included those encoding genes involved in toxin production, genes with oxidoreductase activity, as well as subunits of the vacuolar ATPase complex. Surveys of the functional distribution of gene duplicates indicated that pathogens show enrichment for gene duplicates associated with receptor and hydrolase activities, while euascomycete pathogens appeared to have not only these differences, but also significantly more duplicates associated with regulatory and carbohydrate binding functions.</p> <p>Conclusion</p> <p>Differences in the overall levels of gene duplication in phytopathogenic species <it>versus </it>non-pathogenic relatives implicate gene inventory flux as an important virulence-associated process in fungi. We hypothesize that the observed patterns of gene duplicate enrichment, gene family expansion and contraction reflect adaptation within pathogenic life histories. These adaptations were likely shaped by ancient, as well as contemporary, intimate associations with monocot hosts.</p

    Study of Quark Propagator Solutions to the Dyson--Schwinger Equation in a Confining Model

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    We solve the Dyson--Schwinger equation for the quark propagator in a model with singular infrared behavior for the gluon propagator. We require that the solutions, easily found in configuration space, be tempered distributions and thus have Fourier transforms. This severely limits the boundary conditions that the solutions may satisify. The sign of the dimensionful parameter that characterizes the model gluon propagator can be either positive or negative. If the sign is negative, we find a unique solution. It is singular at the origin in momentum space, falls off like 1/p21/p^2 as p2+/p^2\rightarrow +/-\infty, and it is truly nonperturbative in that it is singular in the limit that the gluon--quark interaction approaches zero. If the sign of the gluon propagator coefficient is positive, we find solutions that are, in a sense that we exhibit, unconstrained linear combinations of advanced and retarded propagators. These solutions are singular at the origin in momentum space, fall off like 1/p21/p^2 asympotically, exhibit ``resonant--like" behavior at the position of the bare mass of the quark when the mass is large compared to the dimensionful interaction parameter in the gluon propagator model, and smoothly approach a linear combination of free--quark, advanced and retarded two--point functions in the limit that the interaction approaches zero. In this sense, these solutions behave in an increasingly ``particle--like" manner as the quark becomes heavy. The Feynman propagator and the Wightman function are not tempered distributions and therefore are not acceptable solutions to the Schwinger--Dyson equation in our model. On this basis we advance several arguments to show that the Fourier--transformable solutions we find are consistent with quark confinement, even though they have singularities on th

    The Production of Hospitable Space: Commercial Propositions and Consumer Co-Creation in a Bar Operation

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    This paper examines the processes through which a commercial bar is transformed into a hospitable space. Drawing on a study of a venue patronized by lesbian, gay, bisexual and transsexual/transgender consumers, it considers how social and commercial forms of hospitality are mobilized. The paper argues that hospitable space has an ideological, normative and situational dimension. More specifically, it suggests the bar’s operation is tied to a set of ideological conceptions, which become the potential basis of association and disassociation among consumers. It examines the forces and processes that shape who participates in the production and consumption of hospitality and how. Finally, it considers the situational, emergent nature of hospitality and the discontinuous production of hospitable space. Rather than focusing exclusively on host-guest or provider-customer relations, which dominates existing work on hospitality, the paper examines how consumers’ perceptions, actions and interactions shape the production of hospitality. By doing so the paper offers an alternative approach to understanding queer spaces, bar operation as well as hospitality

    Assessment of cochlear synaptopathy by electrocochleography to low frequencies in a preclinical model and human subjects

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    Cochlear synaptopathy is the loss of synapses between the inner hair cells and the auditory nerve despite survival of sensory hair cells. The findings of extensive cochlear synaptopathy in animals after moderate noise exposures challenged the long-held view that hair cells are the cochlear elements most sensitive to insults that lead to hearing loss. However, cochlear synaptopathy has been difficult to identify in humans. We applied novel algorithms to determine hair cell and neural contributions to electrocochleographic (ECochG) recordings from the round window of animal and human subjects. Gerbils with normal hearing provided training and test sets for a deep learning algorithm to detect the presence of neural responses to low frequency sounds, and an analytic model was used to quantify the proportion of neural and hair cell contributions to the ECochG response. The capacity to detect cochlear synaptopathy was validated in normal hearing and noise-exposed animals by using neurotoxins to reduce or eliminate the neural contributions. When the analytical methods were applied to human surgical subjects with access to the round window, the neural contribution resembled the partial cochlear synaptopathy present after neurotoxin application in animals. This result demonstrates the presence of viable hair cells not connected to auditory nerve fibers in human subjects with substantial hearing loss and indicates that efforts to regenerate nerve fibers may find a ready cochlear substrate for innervation and resumption of function

    Germline mutations in the oncogene EZH2 cause Weaver syndrome and increased human height.

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    The biological processes controlling human growth are diverse, complex and poorly understood. Genetic factors are important and human height has been shown to be a highly polygenic trait to which common and rare genetic variation contributes. Weaver syndrome is a human overgrowth condition characterised by tall stature, dysmorphic facial features, learning disability and variable additional features. We performed exome sequencing in four individuals with Weaver syndrome, identifying a mutation in the histone methyltransferase, EZH2, in each case. Sequencing of EZH2 in additional individuals with overgrowth identified a further 15 mutations. The EZH2 mutation spectrum in Weaver syndrome shows considerable overlap with the inactivating somatic EZH2 mutations recently reported in myeloid malignancies. Our data establish EZH2 mutations as the cause of Weaver syndrome and provide further links between histone modifications and regulation of human growth

    Measuring the impact and costs of a universal group based parenting programme : protocol and implementation of a trial

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    Background Sub-optimal parenting is a common risk factor for a wide range of negative health, social and educational outcomes. Most parenting programmes have been developed in the USA in the context of delinquency prevention for targeted or indicated groups and the main theoretical underpinning for these programmes is behaviour management. The Family Links Nurturing Programme (FLNP) focuses on family relationships as well as behaviour management and is offered on a universal basis. As a result it may be better placed to improve health and educational outcomes. Developed in the UK voluntary sector, FLNP is popular with practitioners, has impressed policy makers throughout the UK, has been found to be effective in before/after and qualitative studies, but lacks a randomised controlled trial (RCT) evidence base. Methods/Design A multi-centre, investigator blind, randomised controlled trial of the FLNP with a target sample of 288 south Wales families who have a child aged 2-4 yrs living in or near to Flying Start/Sure Start areas. Changes in parenting, parent child relations and parent and child wellbeing are assessed with validated measures immediately and at 6 months post intervention. Economic components include cost consequences and cost utility analyses based on parental ranking of states of quality of life. Attendance and completion rates and fidelity to the FLNP course delivery are assessed. A nested qualitative study will assess reasons for participation and non-participation and the perceived value of the programme to families. By the end of May 2010, 287 families have been recruited into the trial across four areas of south Wales. Recruitment has not met the planned timescales with barriers including professional anxiety about families entering the control arm of the trial, family concern about video and audio recording, programme facilitator concern about the recording of FLNP sessions for fidelity purposes and delays due to the new UK research governance procedures. Discussion Whilst there are strong theoretical arguments to support universal provision of parenting programmes, few universal programmes have been subjected to randomised controlled trials. In this paper we describe a RCT protocol with quantitative and qualitative outcome measures and an economic evaluation designed to provide clear evidence with regard to effectiveness and costs. We describe challenges implementing the protocol and how we are addressing these

    Effective descriptions of branes on non-geometric tori

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    We investigate the low-energy effective description of non-geometric compactifications constructed by T-dualizing two or three of the directions of a T^3 with non-vanishing H-flux. Our approach is to introduce a D3-brane in these geometries and to take an appropriate decoupling limit. In the case of two T-dualities, we find at low energies a non-commutative T^2 fibered non-trivially over an S^1. In the UV this theory is still decoupled from gravity, but is dual to a little string theory with flavor. For the case of three T-dualities, we do not find a sensible decoupling limit, casting doubt on this geometry as a low-energy effective notion in critical string theory. However, by studying a topological toy model in this background, we find a non-associative geometry similar to one found by Bouwknegt, Hannabuss, and Mathai.Comment: 22 pages, 4 figures, references adde
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