Conservative Interventions for mobile Pes Planus in Adults: a systematic review

Background. Adult pes planus (flat foot) is a common problem encountered by many health care professionals. Despite the perception that flat foot can cause pain and impair function, and the availability and widespread use of various treatments, there is no consensus on the optimal treatment strategy. Aim. To assess the effectiveness of conservative (non-surgical) interventions for pes planus in adults. Method. A systematic search of the literature was undertaken. This included: the Cochrane Central Register of Controlled Trials; the CMSG Specialized Trials Register; an electronic search was conducted using MEDLINE (1960 to June 2012), EMBASE (1980 to June 2012), and CINAHL (1982 - June 2012). Specialised journals, trial reference lists and review articles were hand searched. Selection criteria: Randomised or quasi-randomised trials of treatment interventions for pes planus in adults. Trials that included specific pathologies such as plantar heel pain, metatarsal stress fractures, posterior-tibial tendon dysfunction, ankle fractures, rheumatoid foot pathologies, neuromuscular conditions and diabetic foot complications were excluded. Data collection and analysis: Two authors independently screened the search results to identify those meeting the inclusion criteria and quality assessed those included using a checklist based on the Cochrane Collaboration Assessment of Risk of Bias tool. This tool focused on risk of selection, performance, detection, attrition and reporting bias. Results. Four trials, involving 140 subjects, met the inclusion criteria for the review. All four were judged to be at high risk of bias in at least one area, and were also at unclear risk of bias in at least one other area. All scored highly in relation to attrition bias, due to the short follow up times and experimental designs used. Data was not pooled due to the high level of heterogeneity identified in the interventions assessed, participants selected and outcomes measured. The results of one study suggest that after four weeks of use orthoses may result in a significant improvement in medio lateral sway, and may result in improved, although non-significant, general foot-related quality of life (Rome 2004). One study (Redmond 2009) suggests that their effect on plantar pressure distribution in the foot may not be dependent on whether they are custom or prefabricated devices. Although this study identified significant changes in some plantar pressure variables with both custom and prefabricated devices, another (Esterman 2005) failed to find any significant effect of ¾ length prefabricated orthoses on pain, injury incidence, foot health or quality of life in a group of air force recruits. The fourth study (Jung 2009) suggests that exercising the intrinsic foot muscles may enhance the effect of orthoses. Despite these findings, since each study incurred risk of bias in at least one area no conclusions can be drawn

Modelling Semiconductor Pixel Detectors

In this thesis the work will focus on the modelling of highly pixellated solid- state devices. Results are presented on the performance of a pixellated spectroscopic silicon detector - the Dash-E detector. The electronic noise is measured to be 228 eV with the system observed to be close to the Fano limit at room temperature. The characteristic X-rays of Mn-55, Cu, Rb, Mo, Ag and Ba have been used to examine the spectroscopic performance of the detectors. Good linearity over the required energy range 1 keV to 25 keV has been observed. A higher than expected background is evident in all of the spectra taken - approximately a 1:1 correspondence in the peak counts to background counts. The modelled performance of a 3-D GaAs detector is analysed. The effect of the metallic column-like electrode structure on the particle interactions is simulated via the Monte Carlo code MCNP. The effective dead area due to these electrodes is reduced from 8% to 4.5% due to the secondary particle interactions. The modelled structure becomes depleted at 50 V with a slight over-depletion of 75 V necessary to minimise the inter-electrode low field regions. The principle benefit of these depletion voltages is that they remain constant for whatever detection thickness that fabrication allows. The charge transport in the devices are also examined, with the damage effects of dry-etching included - a technique used to form the electrode holes in the GaAs material. Full charge collection can be expected after 200 ps in most cases. The effect of reducing the charge carrier lifetime and examining the charge collection efficiency has been utilised to explore how these detectors would respond in a harsh radiation environment. It is predicted that over critical carrier lifetimes (10 ps to 0.1 ns) an improvement of 40 % over conventional detectors can be expected. This also has positive implications for fabricating detectors, in this geometry, from materials which might otherwise be considered substandard. An analysis of charge transport in CdZnTe pixel detectors has been performed. The analysis starts with simulation studies into the formation of contacts and their influence on the internal electric field of planar detectors. The models include a number of well known defect states and these are balanced to give an agreement with a typical experimental I-V curve. The charge transport study extends to the development of a method for studying the effect of charge sharing in highly pixellated detectors. The case of X-ray, as well as higher energy ?-ray, interactions are considered. The charge lost is studied for these interactions over a range of pixel sizes (1mum to 10 mm). The aforementioned Dash-E detector has been used to obtain experimental data for comparison with the models developed, with close agreement being observed. The combination of MCNP and MEDICI is used to form a complete picture of photon interactions in semiconducting materials and also compares well with experiment. The models predict that the dominant term in the sharing of charge is due to diffusion and that the difference with photon energy is due to the energy given to the photoelectron

Simultaneous electrophysiology and fiber photometry in freely behaving mice

In vivo electrophysiology is the gold standard technique used to investigate sub-second neural dynamics in freely behaving animals. However, monitoring cell-type-specific population activity is not a trivial task. Over the last decade, fiber photometry based on genetically encoded calcium indicators (GECIs) has been widely adopted as a versatile tool to monitor cell-type-specific population activity in vivo. However, this approach suffers from low temporal resolution. Here, we combine these two approaches to monitor both sub-second field potentials and cell-type-specific population activity in freely behaving mice. By developing an economical custom-made system and constructing a hybrid implant of an electrode and a fiber optic cannula, we simultaneously monitor artifact-free mesopontine field potentials and calcium transients in cholinergic neurons across the sleep-wake cycle. We find that mesopontine cholinergic activity co-occurs with sub-second pontine waves, called P-waves, during rapid eye movement sleep. Given the simplicity of our approach, simultaneous electrophysiological recording and cell-type-specific imaging provides a novel and valuable tool for interrogating state-dependent neural circuit dynamics in vivo

Depth-specific optogenetic control in vivo with a scalable, high density µLED neural probe

Controlling neural circuits is a powerful approach to uncover a causal link between neural activity and behaviour. Optogenetics has been widely adopted by the neuroscience community as it offers cell-type-specific perturbation with millisecond precision. However, these studies require light delivery in complex patterns with cellular-scale resolution, while covering a large volume of tissue at depth in vivo. Here we describe a novel high-density silicon-based microscale light-emitting diode (µLED) array, consisting of up to ninety-six 25 µm-diameter µLEDs emitting at a wavelength of 450 nm with a peak irradiance of 400 mW/mm2. A width of 100 µm, tapering to a 1 µm point, and a 40 µm thickness help minimise tissue damage during insertion. Thermal properties permit a set of optogenetic operating regimes, with ~0.5°C average temperature increase. We demonstrate depth-dependent activation of mouse neocortical neurons in vivo, offering an inexpensive novel tool for the precise manipulation of neural activity

Thermal and optical characterization of micro-LED probes for in vivo optogenetic neural stimulation

Within optogenetics there is a need for compact light sources that are capable of delivering light with excellent spatial, temporal, and spectral resolution to deep brain structures. Here, we demonstrate a custom GaN-based LED probe for such applications and the electrical, optical, and thermal properties are analyzed. The output power density and emission spectrum were found to be suitable for stimulating channelrhodopsin-2, one of the most common light-sensitive proteins currently used in optogenetics. The LED device produced high light intensities, far in excess of those required to stimulate the light-sensitive proteins within the neurons. Thermal performance was also investigated, illustrating that a broad range of operating regimes in pulsed mode are accessible while keeping a minimum increase in temperature for the brain (0.5°C). This type of custom device represents a significant step forward for the optogenetics community, allowing multiple bright excitation sites along the length of a minimally invasive neural probe

Contrast sensitivity with a subretinal prosthesis and implications for efficient delivery of visual information

PURPOSE. To evaluate the contrast sensitivity of a degenerate retina stimulated by a photovoltaic subretinal prosthesis, and assess the impact of low contrast sensitivity on transmission of visual information. METHODS. We measure ex vivo the full-field contrast sensitivity of healthy rat retina stimulated with white light, and the contrast sensitivity of degenerate rat retina stimulated with a subretinal prosthesis at frequencies exceeding flicker fusion (>20 Hz). Effects of eye movements on retinal ganglion cell (RGC) activity are simulated using a linear–nonlinear model of the retina. RESULTS. Retinal ganglion cells adapt to high frequency stimulation of constant intensity, and respond transiently to changes in illumination of the implant, exhibiting responses to ON-sets, OFF-sets, and both ON- and OFF-sets of light. The percentage of cells with an OFF response decreases with progression of the degeneration, indicating that OFF responses are likely mediated by photoreceptors. Prosthetic vision exhibits reduced contrast sensitivity and dynamic range, with 65% contrast changes required to elicit responses, as compared to the 3% (OFF) to 7% (ON) changes with visible light. The maximum number of action potentials elicited with prosthetic stimulation is at most half of its natural counterpart for the ON pathway. Our model predicts that for most visual scenes, contrast sensitivity of prosthetic vision is insufficient for triggering RGC activity by fixational eye movements. CONCLUSIONS. Contrast sensitivity of prosthetic vision is 10 times lower than normal, and dynamic range is two times below natural. Low contrast sensitivity and lack of OFF responses hamper delivery of visual information via a subretinal prosthesis

Interactions of prosthetic and natural vision in animals with local retinal degeneration

Prosthetic restoration of partial sensory loss leads to interactions between artificial and natural inputs. Ideally, the rehabilitation should allow perceptual fusion of the two modalities. Here we studied the interactions between normal and prosthetic vision in a rodent model of local retinal degeneration.  Implantation of a photovoltaic array in the subretinal space of normally sighted rats induced local degeneration of the photoreceptors above the chip, and the inner retinal neurons in this area were electrically stimulated by the photovoltaic implant powered by near-infrared (NIR) light. We studied prosthetic and natural visually evoked potentials (VEP) in response to simultaneous stimulation by NIR and visible light patterns.  We demonstrate that electrical and natural VEPs summed linearly in the visual cortex, and both responses decreased under brighter ambient light. Responses to visible light flashes increased over 3 orders of magnitude of contrast (flash/background), while for electrical stimulation the contrast range was limited to 1 order of magnitude. The maximum amplitude of the prosthetic VEP was three times lower than the maximum response to a visible flash over the same area on the retina.  Ambient light affects prosthetic responses, albeit much less than responses to visible stimuli. Prosthetic representation of contrast in the visual scene can be encoded, to a limited extent, by the appropriately calibrated stimulus intensity, which also depends on the ambient light conditions. Such calibration will be important for patients combining central prosthetic vision with natural peripheral sight, such as in age-related macular degeneration

Inner retinal preservation in rat models of retinal degeneration implanted with subretinal photovoltaic arrays

Photovoltaic arrays (PVA) implanted into the subretinal space of patients with retinitis pigmentosa (RP) are designed to electrically stimulate the remaining inner retinal circuitry in response to incident light, thereby recreating a visual signal when photoreceptor function declines or is lost. Preservation of inner retinal circuitry is critical to the fidelity of this transmitted signal to ganglion cells and beyond to higher visual targets. Post-implantation loss of retinal interneurons or excessive glial scarring could diminish and/or eliminate PVA-evoked signal transmission. As such, assessing the morphology of the inner retina in RP animal models with subretinal PVAs is an important step in defining biocompatibility and predicting success of signal transmission. In this study, we used immunohistochemical methods to qualitatively and quantitatively compare inner retinal morphology after the implantation of a PVA in two RP models: the Royal College of Surgeons (RCS) or transgenic S334ter-line 3 (S334ter-3) rhodopsin mutant rat. Two PVA designs were compared. In the RCS rat, we implanted devices in the subretinal space at 4 weeks of age and histologically examined them at 8 weeks of age and found inner retinal morphology preservation with both PVA devices. In the S334ter-3 rat, we implanted devices at 6-12 weeks of age and again, inner retinal morphology was generally preserved with either PVA design 16-26 weeks post-implantation. Specifically, the length of rod bipolar cells and numbers of cholinergic amacrine cells were maintained along with their characteristic inner plexiform lamination patterns. Throughout the implanted retinas we found nonspecific glial reaction, but none showed additional glial scarring at the implant site. Our results indicate that subretinally implanted PVAs are well-tolerated in rodent RP models and that the inner retinal circuitry is preserved, consistent with our published results showing implant-evoked signal transmission

Structured illumination for communications and bioscience using GaN micro-LED arrays interfaced to CMOS

Gallium-Nitride-based light-emitting diodes (LEDs) have emerged over the last two decades as highly energy-efficient, cost-effective, compact and robust light sources. While general purpose lighting has been the dominant application thus far, a variety of other applications can also exploit these advantageous properties, including optical communications, fluorescence sensing and bioscience. Micro-LEDs arrays of individually-addressable LED pixels, each pixel typically 100 µm or less, offer further advantages over conventional LEDs such as extremely high modulation bandwidths and spatio-temporally controllable illumination patterns. These arrays are also readily compatible with flip-chip integration with CMOS electronic driver arrays. Here we report how these CMOS-controlled micro-LED arrays enable “smart lighting” solutions, capable of providing services such as wireless data communication and indoor navigation in conjunction with illumination. We also demonstrate how this smart functionality opens up novel bioscience applications, including depth-specific in-vivo optical neural probes and wireless transfer of measured data