3,220 research outputs found

    Cochlear reimplantation

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    Since its inception in 1988 the Cochlear Implant Programme in Manchester has successfully implanted 69 adults and 23 children. Of these 92 procedures, three patients have undergone revision surgery with the insertion of either a new implant or re-positioning of the existing device. We examine the circumstances that lead to the need for reimplantation in these patients, discuss the technical aspects of revision surgery together with the functional results of such procedures. Re-operatio

    SMARCB1/INI1 germline mutations contribute to 10% of sporadic schwannomatosis

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    <p>Abstract</p> <p>Background</p> <p>Schwannomatosis is a disease characterized by multiple non-vestibular schwannomas. Although biallelic <it>NF2 </it>mutations are found in schwannomas, no germ line event is detected in schwannomatosis patients. In contrast, germline mutations of the <it>SMARCB1 </it>(<it>INI1</it>) tumor suppressor gene were described in familial and sporadic schwannomatosis patients.</p> <p>Methods</p> <p>To delineate the <it>SMARCB1 </it>gene contribution, the nine coding exons were sequenced in a series of 56 patients affected with a variable number of non-vestibular schwannomas.</p> <p>Results</p> <p>Nine variants scattered along the sequence of <it>SMARCB1 </it>were identified. Five of them were classified as deleterious. All five patients carrying a <it>SMARCB1 </it>mutation had more multiple schwannomas, corresponding to 10.2% of patients with schwannomatosis. They were also diagnosed before 35 years of age.</p> <p>Conclusions</p> <p>These results suggest that patients with schwannomas have a significant probability of carrying a <it>SMARCB1 </it>mutation. Combined with data available from other studies, they confirm the clinical indications for genetic screening of the <it>SMARCB1 </it>gene.</p

    PAH mineralization and bacterial organotolerance in surface sediments of the Charleston Harbor estuary

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    Semi-volatile organic compounds (SVOCs) in estuarine waters can adversely affect biota but watershed sources can be difficult to identify because these compounds are transient. Natural bacterial assemblages may respond to chronic, episodic exposure to SVOCs through selection of more organotolerant bacterial communities. We measured bacterial production, organotolerance and polycyclic aromatic hydrocarbon (PAH) mineralization in Charleston Harbor and compared surface sediment from stations near a known, permitted SVOC outfall (pulp mill effluent) to that from more pristine stations. Naphthalene additions inhibited an average of 77% of bacterial metabolism in sediments from the more pristine site (Wando River). Production in sediments nearest the outfall was only inhibited an average of 9% and in some cases, was actually stimulated. In general, the stations with the highest rates of bacterial production also were among those with the highest rates of PAH mineralization. This suggests that the capacity to mineralize PAH carbon is a common feature amongst the bacterial assemblage in these estuarine sediments and could account for an average of 5.6% of bacterial carbon demand (in terms of production) in the summer, 3.3% in the spring (April) and only 1.2% in winter (December)

    The Salmonella Genomic Island 1 Is Specifically Mobilized In Trans by the IncA/C Multidrug Resistance Plasmid Family

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    BACKGROUND: The Salmonella genomic island 1 (SGI1) is a Salmonella enterica-derived integrative mobilizable element (IME) containing various complex multiple resistance integrons identified in several S. enterica serovars and in Proteus mirabilis. Previous studies have shown that SGI1 transfers horizontally by in trans mobilization in the presence of the IncA/C conjugative helper plasmid pR55. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report the ability of different prevalent multidrug resistance (MDR) plasmids including extended-spectrum β-lactamase (ESBL) gene-carrying plasmids to mobilize the multidrug resistance genomic island SGI1. Through conjugation experiments, none of the 24 conjugative plasmids tested of the IncFI, FII, HI2, I1, L/M, N, P incompatibility groups were able to mobilize SGI1 at a detectable level (transfer frequency <10(-9)). In our collection, ESBL gene-carrying plasmids were mainly from the IncHI2 and I1 groups and thus were unable to mobilize SGI1. However, the horizontal transfer of SGI1 was shown to be specifically mediated by conjugative helper plasmids of the broad-host-range IncA/C incompatibility group. Several conjugative IncA/C MDR plasmids as well as the sequenced IncA/C reference plasmid pRA1 of 143,963 bp were shown to mobilize in trans SGI1 from a S. enterica donor to the Escherichia coli recipient strain. Depending on the IncA/C plasmid used, the conjugative transfer of SGI1 occurred at frequencies ranging from 10(-3) to 10(-6) transconjugants per donor. Of particular concern, some large IncA/C MDR plasmids carrying the extended-spectrum cephalosporinase bla(CMY-2) gene were shown to mobilize in trans SGI1. CONCLUSIONS/SIGNIFICANCE: The ability of the IncA/C MDR plasmid family to mobilize SGI1 could contribute to its spread by horizontal transfer among enteric pathogens. Moreover, the increasing prevalence of IncA/C plasmids in MDR S. enterica isolates worldwide has potential implications for the epidemic success of the antibiotic resistance genomic island SGI1 and its close derivatives

    Performance Evaluation of Pseudospectral Ultrasound Simulations on a Cluster of Xeon Phi Accelerators

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    The rapid development of novel procedures in medical ultrasonics, including treatment planning in therapeutic ultrasound and image reconstruction in photoacoustic tomography, leads to increasing demand for large-scale ultrasound simulations. However, routine execution of such simulations using traditional methods, e.g., finite difference time domain, is expensive and often considered intractable due to the computational and memory requirements. The k-space corrected pseudospectral time domain method used by the k-Wave toolbox allows for significant reductions in spatial and temporal grid resolution. These improvements are achieved at the cost of all-to-all communication, which are inherent to the multi-dimensional fast Fourier transforms. To improve data locality, reduce communication and allow efficient use of accelerators, we recently implemented a domain decomposition technique based on a local Fourier basis. In this paper, we investigate whether it is feasible to run the distributed k-Wave implementation on the Salomon cluster equipped with 864 Intel Xeon Phi (Knight’s Corner) accelerators. The results show the immaturity of the KNC platform with issues ranging from limited support of Infiniband and LustreFS in Intel MPI on this platform to poor performance of 3D FFTs achieved by Intel MKL on the KNC architecture. Yet, we show that it is possible to achieve strong and weak scaling comparable to CPU-only platforms albeit with the runtime 1.8× to 4.3× longer. However, the accounting policy for Salomon’s accelerators is far more favorable and thus their employment reduces the computational cost significantly

    Observation of Spontaneous Brillouin Cooling

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    While radiation-pressure cooling is well known, the Brillouin scattering of light from sound is considered an acousto-optical amplification-only process. It was suggested that cooling could be possible in multi-resonance Brillouin systems when phonons experience lower damping than light. However, this regime was not accessible in traditional Brillouin systems since backscattering enforces high acoustical frequencies associated with high mechanical damping. Recently, forward Brillouin scattering in microcavities has allowed access to low-frequency acoustical modes where mechanical dissipation is lower than optical dissipation, in accordance with the requirements for cooling. Here we experimentally demonstrate cooling via such a forward Brillouin process in a microresonator. We show two regimes of operation for the Brillouin process: acoustical amplification as is traditional, but also for the first time, a Brillouin cooling regime. Cooling is mediated by an optical pump, and scattered light, that beat and electrostrictively attenuate the Brownian motion of the mechanical mode.Comment: Supplementary material include

    Electromagnetically Induced Transparency and Slow Light with Optomechanics

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    Controlling the interaction between localized optical and mechanical excitations has recently become possible following advances in micro- and nano-fabrication techniques. To date, most experimental studies of optomechanics have focused on measurement and control of the mechanical subsystem through its interaction with optics, and have led to the experimental demonstration of dynamical back-action cooling and optical rigidity of the mechanical system. Conversely, the optical response of these systems is also modified in the presence of mechanical interactions, leading to strong nonlinear effects such as Electromagnetically Induced Transparency (EIT) and parametric normal-mode splitting. In atomic systems, seminal experiments and proposals to slow and stop the propagation of light, and their applicability to modern optical networks, and future quantum networks, have thrust EIT to the forefront of experimental study during the last two decades. In a similar fashion, here we use the optomechanical nonlinearity to control the velocity of light via engineered photon-phonon interactions. Our results demonstrate EIT and tunable optical delays in a nanoscale optomechanical crystal device, fabricated by simply etching holes into a thin film of silicon (Si). At low temperature (8.7 K), we show an optically-tunable delay of 50 ns with near-unity optical transparency, and superluminal light with a 1.4 microseconds signal advance. These results, while indicating significant progress towards an integrated quantum optomechanical memory, are also relevant to classical signal processing applications. Measurements at room temperature and in the analogous regime of Electromagnetically Induced Absorption (EIA) show the utility of these chip-scale optomechanical systems for optical buffering, amplification, and filtering of microwave-over-optical signals.Comment: 15 pages, 9 figure

    Bone Is Not Essential for Osteoclast Activation

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    Background: The mechanism whereby bone activates resorptive behavior in osteoclasts, the cells that resorb bone, is unknown. It is known that avb3 ligands are important, because blockade of avb3 receptor signaling inhibits bone resorption, but this might be through inhibition of adhesion or migration rather than resorption itself. Nor is it known whether avb3 ligands are sufficient for resorption the consensus is that bone mineral is essential for the recognition of bone as the substrate appropriate for resorption. Methodology/Principal Findings: Vitronectin- but not fibronectin-coated coverslips induced murine osteoclasts to secrete tartrate-resistant acid phosphatase, as they do on bone. Osteoclasts incubated on vitronectin, unlike fibronectin, formed podosome belts on glass coverslips, and these were modulated by resorption-regulating cytokines. Podosome belts formed on vitronectin-coated surfaces whether the substrates were rough or smooth, rigid or flexible. We developed a novel approach whereby the substrate-apposed surface of cells can be visualized in the scanning electron microscope. With this approach, supported by transmission electron microscopy, we found that osteoclasts on vitronectin-coated surfaces show ruffled borders and clear zones characteristic of resorbing osteoclasts. Ruffles were obscured by a film if cells were incubated in the cathepsin inhibitor E64, suggesting that removal of the film represents substrate-degrading behavior. Analogously, osteoclasts formed resorption-like trails on vitronectin-coated substrates. Like bone resorption, these trails were dependent upon resorbogenic cytokines and were inhibited by E64. Bone mineral induced actin rings and surface excavation only if first coated with vitronectin. Fibronectin could not substitute in any of these activities, despite enabling adhesion and cell spreading. Conclusions/Significance: Our results show that ligands avb3 are not only necessary but sufficient for the induction of resorptive behavior in osteoclasts; and suggest that bone is recognized through its affinity for these ligands, rather than by its mechanical or topographical attributes, or through a putative ‘mineral receptor’

    Stability, Entrapment and Variant Formation of Salmonella Genomic Island 1

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    <div><h3>Background</h3><p>The <em>Salmonella</em> genomic island 1 (SGI1) is a 42.4 kb integrative mobilizable element containing several antibiotic resistance determinants embedded in a complex integron segment In104. The numerous SGI1 variants identified so far, differ mainly in this segment and the explanations of their emergence were mostly based on comparative structure analyses. Here we provide experimental studies on the stability, entrapment and variant formation of this peculiar gene cluster originally found in <em>S</em>. Typhimurium.</p> <h3>Methodology/Principal Findings</h3><p>Segregation and conjugation tests and various molecular techniques were used to detect the emerging SGI1 variants in <em>Salmonella</em> populations of 17 <em>Salmonella enterica</em> serovar Typhimurium DT104 isolates from Hungary. The SGI1s in these isolates proved to be fully competent in excision, conjugal transfer by the IncA/C helper plasmid R55, and integration into the <em>E. coli</em> chromosome. A trap vector has been constructed and successfully applied to capture the island on a plasmid. Monitoring of segregation of SGI1 indicated high stability of the island. SGI1-free segregants did not accumulate during long-term propagation, but several SGI1 variants could be obtained. Most of them appeared to be identical to SGI1-B and SGI1-C, but two new variants caused by deletions via a short-homology-dependent recombination process have also been detected. We have also noticed that the presence of the conjugation helper plasmid increased the formation of these deletion variants considerably.</p> <h3>Conclusions/Significance</h3><p>Despite that excision of SGI1 from the chromosome was proven in SGI1<sup>+</sup><em>Salmonella</em> populations, its complete loss could not be observed. On the other hand, we demonstrated that several variants, among them two newly identified ones, arose with detectable frequencies in these populations in a short timescale and their formation was promoted by the helper plasmid. This reflects that IncA/C helper plasmids are not only involved in the horizontal spreading of SGI1, but may also contribute to its evolution.</p> </div

    Trapped in the prison of the mind: notions of climate-induced (im)mobility decision-making and wellbeing from an urban informal settlement in Bangladesh

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    The concept of Trapped Populations has until date mainly referred to people ‘trapped’ in environmentally high-risk rural areas due to economic constraints. This article attempts to widen our understanding of the concept by investigating climate-induced socio-psychological immobility and its link to Internally Displaced People’s (IDPs) wellbeing in a slum of Dhaka. People migrated here due to environmental changes back on Bhola Island and named the settlement Bhola Slum after their home. In this way, many found themselves ‘immobile’ after having been mobile—unable to move back home, and unable to move to other parts of Dhaka, Bangladesh, or beyond. The analysis incorporates the emotional and psychosocial aspects of the diverse immobility states. Mind and emotion are vital to better understand people’s (im)mobility decision-making and wellbeing status. The study applies an innovative and interdisciplinary methodological approach combining Q-methodology and discourse analysis (DA). This mixed-method illustrates a replicable approach to capture the complex state of climate-induced (im)mobility and its interlinkages to people’s wellbeing. People reported facing non-economic losses due to the move, such as identity, honour, sense of belonging and mental health. These psychosocial processes helped explain why some people ended up ‘trapped’ or immobile. The psychosocial constraints paralysed them mentally, as well as geographically. More empirical evidence on how climate change influences people’s wellbeing and mental health will be important to provide us with insights in how to best support vulnerable people having faced climatic impacts, and build more sustainable climate policy frameworks
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