Adjustable prosthetic sockets: a systematic review of industrial and research design characteristics and their justifications.

BackgroundThe prosthetic socket is a key component that influences prosthesis satisfaction, with a poorly fitting prosthetic socket linked to prosthesis abandonment and reduced community participation. This paper reviews adjustable socket designs, as they have the potential to improve prosthetic fit and comfort through accommodating residual limb volume fluctuations and alleviating undue socket pressure.MethodsSystematic literature and patent searches were conducted across multiple databases to identify articles and patents that discussed adjustable prosthetic sockets. The patents were used to find companies, organisations, and institutions who currently sell adjustable sockets or who are developing devices.Results50 literature articles and 63 patents were identified for inclusion, representing 35 different designs used in literature and 16 commercially available products. Adjustable sockets are becoming more prevalent with 73% of publications (literature, patents, and news) occurring within the last ten years. Two key design characteristics were identified: principle of adjustability (inflatable bladders, moveable panels, circumferential adjustment, variable length), and surface form (conformable, rigid multi-DOF, and rigid single DOF). Inflatable bladders contributed to 40% of literature used designs with only one identified commercially available design (n = 16) using this approach. Whereas circumferential adjustment designs covered 75% of identified industry designs compared to only 36% of literature devices. Clinical studies were generally small in size and only 17.6% of them assessed a commercially available socket.DiscussionThere are clear differences in the design focus taken by industry and researchers, with justification for choice of design and range of adjustment often being unclear. Whilst comfort is often reported as improved with an adjustable socket, the rationale behind this is not often discussed, and small study sizes reduce the outcome viability. Many adjustable sockets lack appropriate safety features to limit over or under tightening, which may present a risk of tissue damage or provide inadequate coupling, affecting function and satisfaction. Furthermore, the relationship between design and comfort or function are rarely investigated and remain a significant gap in the literature. Finally, this review highlights the need for improved collaboration between academia and industry, with a strong disconnect observed between commercial devices and published research studies

Integrins as therapeutic targets: lessons and opportunities.

The integrins are a large family of cell adhesion molecules that are essential for the regulation of cell growth and function. The identification of key roles for integrins in a diverse range of diseases, including cancer, infection, thrombosis and autoimmune disorders, has revealed their substantial potential as therapeutic targets. However, so far, pharmacological inhibitors for only three integrins have received marketing approval. This article discusses the structure and function of integrins, their roles in disease and the chequered history of the approved integrin antagonists. Recent advances in the understanding of integrin function, ligand interaction and signalling pathways suggest novel strategies for inhibiting integrin function that could help harness their full potential as therapeutic targets

Near-infrared fluorescent imaging using BF2-azadipyrromethenes

Movement towards the near infra-red(NIR)region for biological imaging is optimal as there is less auto fluorescence generated from the biological sample, minimal photo damage and greater tissue penetration in this long wavelength region. Therefore, efficient and fast delivery of fluorophores to cells in this region is desired. To begin, the directed self-assembly between a hydrophobic BF2-azadipyrromethene NIR fluorophore and an amphiphilic poloxamer was used to form a nanoparticle that successfully delivered to cellswith a fluorescence response upon uptake. The photophysical properties of the nanoparticle and its ability to deliver to cells was investigated. The emissionof the fluorophore was quenched when part of the nanoparticle but switchedon when in a lipophilic environment. The location of the fluorophore emission within the cell was monitored with selective emission seen first inside lipid droplets at 1 hr followed by other membrane regions at 24 hr. The fluorophore was photostable inside the cell allowing for prolonged continuous imaging of the motion and biogenesis of lipid droplets over time.  Once a successful delivery method was developed, a range of BF2-azadipyrromethenes were next investigated for their ability to work with super resolution imaging. Mainly their ability to work in conjunction with a stimulated emission depletion laser in the NIR was explored. A method to screen a variety of fluorophores for their “stedability” without having to perform cell work was developed allowing for fast probing of different fluorophores. Once screened, the fluorophores were delivered to cells and underwent successful STED imaging with measurements taken of lipophilic structures that had a resolution below the diffraction limit of a confocal microscope. Though one fluorophore was unable to undergo STED imaging, itsability to form an image through anti-stokes emission was achieved.  Next, the ability of a BF2-azadipyrromethene fluorophore to emit in two fluorescence regions simultaneously was investigated. Unlike the previous studies the fluorophore used contained a hydrophobic region and a hydrophilic region (sulfonic acid groups) making it soluble in waterand giving it the ability to aggregate. The aggregation properties of the fluorophore in many environments was investigated,showing an ability to form a J-aggregate that emitted at longer wavelengths then its monomeric form. This dual emission was utilised for fluorescence guided surgery leading to lymphatic mapping at 700 and 800 nm. Overall, the NIR BF2-azadipyrromethenes photophysical properties were utilised for a variety of different imaging techniques allowing for further understanding of biological processes</p

Measuring transtibial prosthetic socket-to-residuum interface coupling in gait using 3D motion capture

Fit and function of a prosthetic socket are often reported as the main reason for dissatisfaction within lower-limb amputees [1,2], leading to further reductions in mobility. One way of measuring the performance of a prosthetic socket is through analysing the socket-to-residuum interface coupling, which describes how the prosthesis changes in pose relative to the residuum. Although motion capture currently measures fewer degrees of freedom (DOF) than X-rays, it is predominantly used due to its reduced risk to participants and its ability to analyse dynamic tasks. However, some recent methodologies proposed still require bespoke prosthetic sockets to allow visibility of reflective markers placed on the liner or residuum [3,4]. Tang, et al. [5] removed this requirement by calculating three of DOF of movement of a virtual residuum for a transfemoral amputee

Identifying STEDable BF₂-Azadipyrromethene Fluorophores

BF2-azadipyrromethenes are highly versatile fluorophores used for cellular and in vivo imaging in the near-infrared and far-red regions of the spectrum. As of yet, their use in conjunction with super-resolution imaging methodologies has not been explored. In this report, a series of structurally related BF2-azadipyrromethenes has been examined for their suitability for use with stimulated emission depletion (STED) nanoscopy. The potential for STED imaging was initially evaluated using aqueous solutions of fluorophores as an effective predictor of fluorophore suitability. For live cell STED imaging in both 2D and 3D, several far-red emitting BF2-azadipyrromethenes were successfully employed. Image resolution below the diffraction limit of a confocal microscope was demonstrated through measurement of distinct intracellular features including the nuclear membrane, nuclear lamina invaginations, the endoplasmic reticulum, and vacuoles. As the STED ability of BF2-azadipyrromethene fluorophores has now been established, their use with this super-resolution method may be expected to increase in the future

Identifying STEDable BF2-Azadipyrromethene Fluorophores

BF2-azadipyrromethenes are highly versatile fluorophores used for cellular and in vivo imaging in the near-infrared and far-red regions of the spectrum. As of yet, their use in conjunction with super-resolution imaging methodologies has not been explored. In this report, a series of structurally related BF2-azadipyrromethenes has been examined for their suitability for use with stimulated emission depletion (STED) nanoscopy. The potential for STED imaging was initially evaluated using aqueous solutions of fluorophores as an effective predictor of fluorophore suitability. For live cell STED imaging in both 2D and 3D, several far-red emitting BF2-azadipyrromethenes were successfully employed. Image resolution below the diffraction limit of a confocal microscope was demonstrated through measurement of distinct intracellular features including the nuclear membrane, nuclear lamina invaginations, the endoplasmic reticulum, and vacuoles. As the STED ability of BF2-azadipyrromethene fluorophores has now been established, their use with this super-resolution method may be expected to increase in the future

Identifying STEDable BF2-azadipyrromethene fluorophores

BF2-azadipyrromethenes are highly versatile fluorophores used for cellular and in vivo imaging in the near-infrared and far-red regions of the spectrum. As of yet, their use in conjunction with super-resolution imaging methodologies has not been explored. In this report, a series of structurally related BF2-azadipyrromethenes has been examined for their suitability for use with stimulated emission depletion (STED) nanoscopy. The potential for STED imaging was initially evaluated using aqueous solutions of fluorophores as an effective predictor of fluorophore suitability. For live cell STED imaging in both 2D and 3D, several far-red emitting BF2-azadipyrromethenes were successfully employed. Image resolution below the diffraction limit of a confocal microscope was demonstrated through measurement of distinct intracellular features including the nuclear membrane, nuclear lamina invaginations, the endoplasmic reticulum, and vacuoles. As the STED ability of BF2-azadipyrromethene fluorophores has now been established, their use with this super-resolution method may be expected to increase in the future

The European Securities and Markets Authority and institutional design for the EU financial market – a tale of two competences: Part (2) rules in action

The purpose of this article, and of its earlier companion article (Part (1) Rule-making, 12 European Business Organization Law Review (2011) p. 41), is to examine the implications of the new European Securities and Markets Authority which was established in January 2011. In the wake of the financial crisis, the case for institutional reform and for conferring regulatory and supervisory powers on a central EU authority became compelling. But any institutional design would have struggled given the necessity for compromise. The central difficulty is one of nuance. Where on the spectrum from national powers to EU powers, and with respect to regulation and supervision, should any new body's powers be placed if optimum outcomes are to be achieved? The question is further complicated by the different dynamics and risks of centralising rule-making and of centralising supervision, even if there is considerable symbiosis between these activities. This article considers ESMA's supervisory powers. It argues that, by contrast with its rule-making powers, the current and potential extent of ESMA's supervisory powers has pushed ESMA too high up the spectrum towards EU intervention. Local supervision of the EU rule-book represents an important safety valve for the EU financial market but this safety valve may be obstructed by ESMA's undue standardisation of supervisory practices. ESMA's extensive direct supervisory powers are also troubling given concerns as to their effectiveness. It was always going to be a challenge to draw the dividing line between ESMA's supervisory powers and those of national competent authorities. But the line may have been drawn too far on the side of operational centralisation

Exploiting Directed Self-Assembly and Disassembly for off-to-on Fluorescence Responsive Live Cell Imaging

A bio-responsive nanoparticle was formed by the directed self-assembly (DSA) of a hydrophobic NIR-fluorophore with poloxamer P188. Fluorophore emission was switched off when part of the nanoparticle, however upon stimulus induced nanoparticle dis-assembly the emission switched on. The emission quenching was shown to be due to fluorophore hydration and aggregation within the nanoparticle and the turn on response attributable to nanoparticle disassembly with embedding of the fluorophore within lipophilic environments. This was exploited for temporal and spatial live cell imaging with a measurable fluorescence response seen upon intracellular delivery of the fluorophore. The first dynamic response, seen within minutes, was from lipid droplets with other lipophilic regions such as the endoplasmic reticulum, nuclear membranes and secretory vacuoles imageable after hours. The high degree of fluorophore photostability facilitated continuous imaging for extended periods and the off to on switching facilitated the real-time observation of lipid droplet biogenesis as they emerged from the endoplasmic reticulum. With an in-depth understanding of the principles involved, further assembly controlling functional responses could be anticipated