Regulating a Benzodifuran Single Molecule Redox Switch via Electrochemical Gating and Optimization of Molecule/Electrode Coupling

We report a novel strategy for the regulation of charge transport through single molecule junctions via the combination of external stimuli of electrode potential, internal modulation of molecular structures, and optimization of anchoring groups. We have designed redox-active benzodifuran (BDF) compounds as functional electronic units to fabricate metal–molecule–metal (m–M–m) junction devices by scanning tunneling microscopy (STM) and mechanically controllable break junctions (MCBJ). The conductance of thiol-terminated BDF can be tuned by changing the electrode potentials showing clearly an off/on/off single molecule redox switching effect. To optimize the response, a BDF molecule tailored with carbodithioate (−CS2–) anchoring groups was synthesized. Our studies show that replacement of thiol by carbodithioate not only enhances the junction conductance but also substantially improves the switching effect by enhancing the on/off ratio from 2.5 to 8.

Manual Electrode Array Insertion Through a Robot-assisted Minimal Invasive Cochleostomy: Feasibility and Comparison of Two Different Electrode Array Subtypes.

HYPOTHESIS To evaluate the feasibility and the results of insertion of two types of electrode arrays in a robotically assisted surgical approach. BACKGROUND Recent publications demonstrated that robot-assisted surgery allows the implantation of free-fitting electrode arrays through a cochleostomy drilled via a narrow bony tunnel (DCA). We investigated if electrode arrays from different manufacturers could be used with this approach. METHODS Cone-beam CT imaging was performed on fivecadaveric heads after placement of fiducial screws. Relevant anatomical structures were segmented and the DCA trajectory, including the position of the cochleostomy, was defined to target the center of the scala tympani while reducing the risk of lesions to the facial nerve. Med-El Flex 28 and Cochlear CI422 electrodes were implanted on both sides, and their position was verified by cone-beam CT. Finally, temporal bones were dissected to assess the occurrence of damage to anatomical structures during DCA drilling. RESULTS The cochleostomy site was directed in the scala tympani in 9 of 10 cases. The insertion of electrode arrays was successful in 19 of 20 attempts. No facial nerve damage was observed. The average difference between the planned and the postoperative trajectory was 0.17 ± 0.19 mm at the level of the facial nerve. The average depth of insertion was 305.5 ± 55.2 and 243 ± 32.1 degrees with Med-El and Cochlear arrays, respectively. CONCLUSIONS Robot-assisted surgery is a reliable tool to allow cochlear implantation through a cochleostomy. Technical solutions must be developed to improve the electrode array insertion using this approach.

Prognostic significance of foveal capillary drop-out and previous panretinal photocoagulation for diabetic macular oedema treated with ranibizumab

AIMS To investigate the prognostic significance of macular capillary drop-out and previous panretinal laser photocoagulation in diabetic macular oedema treated with intravitreal ranibizumab. METHODS Retrospective observational case series. Treatment-naive patients with diabetic macular oedema that had been treated with intravitreal ranibizumab as per the RESTORE study protocol for at least 12 months were included. Some patients (n=15) had previous panretinal laser photocoagulation. Best-corrected visual acuity and central retina thickness were recorded monthly. The foveal avascular zone and the perifoveal capillaries were quantitatively and qualitatively assessed on fluorescein angiography on two occasions during the observational period. RESULTS From the 46 eyes (46 patients) in this study, 13 (28%) had evidence of perifoveal capillary drop-out. Central retinal thickness was significantly thinner at baseline (p=0.02) and throughout the study period in these eyes compared with those with normal perifoveal capillaries. Both groups responded with a significant gain of best-corrected visual acuity to ranibizumab treatment (7.6±3.3 and 6.3±1.3 ETDRS letters, respectively). Eyes with previous panretinal laser photocoagulation displayed a comparable final outcome regarding function and morphology, requiring a similar intensity of intravitreal injections. CONCLUSIONS Perifoveal capillary drop-out did not limit the gain of visual acuity from intravitreal ranibizumab treatment. The reduction of central retina thickness was similar to that seen in eyes with normal perifoveal capillaries. Central retinal thickness in eyes with perifoveal capillary drop-out was generally reduced. However, this did not affect their benefit from treatment. Ranibizumab did not increase the amount of perifoveal capillary loss.

Morphological alterations in the liver of yellow perch (Perca flavescens) from a biological mercury hotspot

Mercury (Hg) contamination is a global issue due to its anthropogenic release, long-range transport, and deposition in remote areas. In Kejimkujik National Park and National Historic Site, Nova Scotia, Canada, high concentrations of total mercury (THg) were found in tissues of yellow perch (Perca flavescens). The aim of this study was to evaluate a possible relationship between THg concentrations and the morphology of perch liver as a main site of metal storage and toxicity. Yellow perch were sampled from five lakes known to contain fish representing a wide range in Hg concentrations in fall 2013. The ultrastructure of hepatocytes and the distribution of Hg within the liver parenchyma were analyzed by transmission electron microscopy (TEM) and electron energy loss spectrometry (EELS). The relative area of macrophage aggregates (MAs) in the liver was determined using image analysis software and fluorescence microscopy. No relation between general health indicators (Fulton's condition index) and THg was observed. In line with this, TEM examination of the liver ultrastructure revealed no prominent pathologies related to THg accumulation. However, a morphological parameter that appeared to increase with muscle THg was the relative area of MAs in the liver. The hepatic lysosomes appeared to be enlarged in samples with the highest THg concentrations. Interestingly, EELS analysis revealed that the MAs and hepatic lysosomes contained Hg.

Rapid drop in the reproduction number during the Ebola outbreak in the Democratic Republic of Congo.

The Democratic Republic of Congo (DRC) experienced a confined rural outbreak of Ebola virus disease (EVD) with 69 reported cases from July to October 2014. Understanding the transmission dynamics during the outbreak can provide important information for anticipating and controlling future EVD epidemics. I fitted an EVD transmission model to previously published data of this outbreak and estimated the basic reproduction number R 0 = 5.2 (95% CI [4.0-6.7]). The model suggests that the net reproduction number Rt fell below unity 28 days (95% CI [25-34] days) after the onset of symptoms in the index case. This study adds to previous epidemiological descriptions of the 2014 EVD outbreak in DRC, and is consistent with the notion that a rapid implementation of control interventions helped reduce further spread.

Lamb Temporal Bone as a Surgical Training Model of Round Window Cochlear Implant Electrode Insertion

OBJECTIVE The preservation of residual hearing in cochlear implantation opens the door for optimal functional results. This atraumatic surgical technique requires training; however, the traditional human cadaveric temporal bones have become less available or unattainable in some institutions. This study investigates the suitability of an alternative model, using cadaveric lamb temporal bone, for surgical training of atraumatic round window electrode insertion. INTERVENTION A total of 14 lamb temporal bones were dissected for cochlear implantation by four surgeons. After mastoidectomy, visualization, and drilling of the round window niche, an atraumatic round window insertion of a Medel Flex24 electrode was performed. Electrode insertion depth and position were verified by computed tomography scans. MAIN OUTCOME MEASURE All cochleas were successfully implanted using the atraumatic round window approach; however, surgical access through the mastoid was substantially different when compared human anatomy. The mean number of intracochlear electrode contacts was 6.5 (range, 4-11) and the mean insertion depth 10.4 mm (range, 4-20 mm), which corresponds to a mean angular perimodiolar insertion depth of 229 degrees (range 67-540°). Full insertion of the electrode was not possible because of the smaller size of the lamb cochlea in comparison to that of the human. CONCLUSION The lamb temporal bone model is well suited as a training model for atraumatic cochlear implantation at the level of the round window. The minimally pneumatized mastoid as well as the smaller cochlea can help prepare a surgeon for difficult cochlear implantations. Because of substantial differences to human anatomy, it is not an adequate training model for other surgical techniques such as mastoidectomy and posterior tympanotomy as well as full electrode insertion.

Characterization of the Capacitance of a Rotating Ring–Disk Electrode

The use of rotating ring–disk electrodes as generator-collector systems has so far been limited to the detection of Faradaic currents at the ring. As opposed to other generator-collector configurations, non-Faradaic detection has not yet been carried out with rotating ring–disk electrodes. In this study, a.c. perturbation based detection for measurement of the ring impedance is introduced. By using a conducting polymer-modified disk electrode in combination with a bare gold ring as a model, it is shown that the measured ring capacitance correlates with the polarization of the polymer film, most probably due to counter-ion exchange. A method of calculating the ring capacitance based on a small-signal sinusoid perturbation is described and the most important instrumental limitations are identified.

Cytotoxicity evaluation of polymer-derived ceramics for pacemaker electrode applications.

Ceramics are known to be chemically stable, and the possibility to electrically dope polymer-derived ceramics makes it a material of interest for implantable electrode applications. We investigated cytotoxic characteristics of four polymer-derived ceramic candidates with either electrically conductive or insulating properties. Cytotoxicity was assessed by culturing C2C12 myoblast cells under two conditions: by exposing them to material extracts and by putting them directly in contact with material samples. Cell spreading was optically evaluated by comparing microscope observations immediately after the materials insertion and after 24 h culturing. Cell viability (MTT) and mortality (LDH) were quantified after 24-h incubation in contact with the materials. Comparison was made with biocompatible positive references (alumina, platinum, biocompatible stainless steel 1.4435), negative references (latex, stainless steel 1.4301) and controls (no material present in the culture wells). We found that the cytotoxic properties of tested ceramics are comparable to established reference materials. These ceramics, which are reported to be very stable, can be microstructured and electrically doped to a wide range of conductivity and are thus excellent candidates for implantable electrode applications including pacemakers.

Response profiles of murine spiral ganglion neurons on multi-electrode arrays.

OBJECTIVE Cochlear implants (CIs) have become the gold standard treatment for deafness. These neuroprosthetic devices feature a linear electrode array, surgically inserted into the cochlea, and function by directly stimulating the auditory neurons located within the spiral ganglion, bypassing lost or not-functioning hair cells. Despite their success, some limitations still remain, including poor frequency resolution and high-energy consumption. In both cases, the anatomical gap between the electrode array and the spiral ganglion neurons (SGNs) is believed to be an important limiting factor. The final goal of the study is to characterize response profiles of SGNs growing in intimate contact with an electrode array, in view of designing novel CI devices and stimulation protocols, featuring a gapless interface with auditory neurons. APPROACH We have characterized SGN responses to extracellular stimulation using multi-electrode arrays (MEAs). This setup allows, in our view, to optimize in vitro many of the limiting interface aspects between CIs and SGNs. MAIN RESULTS Early postnatal mouse SGN explants were analyzed after 6-18 days in culture. Different stimulation protocols were compared with the aim to lower the stimulation threshold and the energy needed to elicit a response. In the best case, a four-fold reduction of the energy was obtained by lengthening the biphasic stimulus from 40 μs to 160 μs. Similarly, quasi monophasic pulses were more effective than biphasic pulses and the insertion of an interphase gap moderately improved efficiency. Finally, the stimulation with an external electrode mounted on a micromanipulator showed that the energy needed to elicit a response could be reduced by a factor of five with decreasing its distance from 40 μm to 0 μm from the auditory neurons. SIGNIFICANCE This study is the first to show electrical activity of SGNs on MEAs. Our findings may help to improve stimulation by and to reduce energy consumption of CIs and thereby contribute to the development of fully implantable devices with better auditory resolution in the future.

Bilateral deep brain stimulation: the placement of the second electrode is not necessarily less accurate than that of the first one.

BACKGROUND Deep brain stimulation (DBS) is recognized as an effective treatment for movement disorders. We recently changed our technique, limiting the number of brain penetrations to three per side. OBJECTIVES The first aim was to evaluate the electrode precision on both sides of surgery since we implemented this surgical technique. The second aim was to analyse whether or not the electrode placement was improved with microrecording and macrostimulation. METHODS We retrospectively reviewed operation protocols and MRIs of 30 patients who underwent bilateral DBS. For microrecording and macrostimulation, we used three parallel channels of the 'Ben Gun' centred on the MRI-planned target. Pre- and post-operative MRIs were merged. The distance between the planned target and the centre of the implanted electrode artefact was measured. RESULTS There was no significant difference in targeting precision on both sides of surgery. There was more intra-operative adjustment of the second electrode positioning based on microrecording and macrostimulation, which allowed to significantly approach the MRI-planned target on the medial-lateral axis. CONCLUSION There was more electrode adjustment needed on the second side, possibly in relation with brain shift. We thus suggest performing a single central track with electrophysiological and clinical assessment, with multidirectional exploration on demand for suboptimal clinical responses.

3D-modeling of Mercury's solar wind sputtered surface-exosphere environment

The efficiency of sputtered refractory elements by H+ and He++ solar wind ions from Mercury's surface and their contribution to the exosphere are studied for various solar wind conditions. A 3D solar wind-planetary interaction hybrid model is used for the evaluation of precipitation maps of the sputter agents on Mercury's surface. By assuming a global mineralogical surface composition, the related sputter yields are calculated by means of the 2013 SRIM code and are coupled with a 3D exosphere model. Because of Mercury's magnetic field, for quiet and nominal solar wind conditions the plasma can only precipitate around the polar areas, while for extreme solar events (fast solar wind, coronal mass ejections, interplanetary magnetic clouds) the solar wind plasma has access to the entire dayside. In that case the release of particles form the planet's surface can result in an exosphere density increase of more than one order of magnitude. The corresponding escape rates are also about an order of magnitude higher. Moreover, the amount of He++ ions in the precipitating solar plasma flow enhances also the release of sputtered elements from the surface in the exosphere. A comparison of our model results with MESSENGER observations of sputtered Mg and Ca elements in the exosphere shows a reasonable quantitative agreement. (C) 2015 Elsevier Ltd. All rights reserved.