Exploring the improvement of human cell cryopreservation

Regenerative medicine is an emerging technology and with hundreds of cell therapies currently in clinical trials there is a need to expand the limited knowledge related to their storage, shipment and preservation. The most widely used medium for human cell cryopreservation is 10%wt dimethyl sulfoxide (DMSO) in serum. However given its potential toxicity, DMSO usage is a key issue in cryopreservation. Methods specify the need to reduce cell exposure time to DMSO above 0°C as much as possible but the maximum amount of time cells can be exposed to DMSO to prevent a detrimental effect needs to be clarified. There are also regulatory issues and concerns with the xenotoxicity, ethics and supply of the other core component in the standard cryomedia formulation: Foetal Bovine Serum (FBS). Developing a viable alternative to FBS is crucial. In cryobiology literature thawing appears poorly understood. A stable process is as vital as freezing to prevent injury to cells. Protocols are currently too vague for cell therapy regulation and need improvement. The time dependent DMSO cytotoxicity was evaluated by overexposing cells to DMSO during and/or after cryopreservation. A broad investigation found that after 1 hour overexposure post thaw viability of human mesenchymal stem cells (hMSCs) was reduced from 96.3±0.6% to 74.1±4.0% and the co-expression of five key hMSC markers was changed from 97.9±1.3% to 68.3±2.6%. This significant change could cause indicate a change in product efficacy and affect patient health, to prevent this, DMSO exposure must be kept to below 1 hour. A range of alternative vehicle solutions were screened and human platelet lysate (hPL) investigated as an alternative. In depth experimentation with hPL as a cryopreservation vehicle solution and culture supplement (in place of FBS) found it to be a worthy, statistically similar alternative. With no xenological or ethical concerns, lower costs than other serum-free alternatives hPL could allow for a move away from xenological components. A heat transfer model was developed and determined that 720J is required to thaw a vial. Using the heat transfer model and additional factors such as pre-thaw stabilisation and on thaw dilution, a two-stage experiment found that the current standard process (warming in a 37°C waterbath) within the current paradigm of a 1.8mL cryovial is optimal but further work is required to define the process for scaled-up product

Characterization of an unanticipated indium-sulfur metallocycle complex

We have produced a novel indium-based metallocycle complex (In-MeSH), which we initially observed as an unanticipated side-product in metal–organic framework (MOF) syntheses. The serendipitously synthesized metallocycle forms via the acid-catalysed decomposition of dimethyl sulfoxide (DMSO) during solvothermal reactions in the presence of indium nitrate, dimethylformamide and nitric acid. A search through the Cambridge Structural Database revealed isostructural zinc, ruthenium and palladium metallocycle complexes formed by other routes. The ruthenium analogue is catalytically active and the In-MeSH structure similarly displays accessible open metal sites around the outside of the ring. Furthermore, this study also gives access to the relatively uncommon oxidation state of In(II), the targeted synthesis of which can be challenging. In(II) complexes have been reported as having potentially important applications in areas such as catalytic water splitting

Welding wire pressure sensor assembly

The present invention relates to a device which is used to monitor the position of a filler wire relative to a base material being welded as the filler wire is added to a welding pool. The device is applicable to automated welding systems wherein nonconsumable electrode arc welding processes are utilized in conjunction with a filler wire which is added to a weld pool created by the electrode arc. The invention senses pressure deviations from a predetermined pressure between the filler wire and the base material, and provides electrical signals responsive to the deviations for actuating control mechanisms in an automatic welding apparatus so as to minimize the pressure deviation and to prevent disengagement of the contact between the filler wire and the base material

A model-based cost-utility analysis of multi-professional simulation training in obstetric emergencies

ObjectiveTo determine the cost-utility of a multi-professional simulation training programme for obstetric emergencies-Practical Obstetric Multi-Professional Training (PROMPT)-with a particular focus on its impact on permanent obstetric brachial plexus injuries (OBPIs).DesignA model-based cost-utility analysis.SettingMaternity units in England.PopulationSimulated cohorts of individuals affected by permanent OBPIs.MethodsA decision tree model was developed to estimate the cost-utility of adopting annual, PROMPT training (scenario 1a) or standalone shoulder dystocia training (scenario 1b) in all maternity units in England compared to current practice, where only a proportion of English units use the training programme (scenario 2). The time horizon was 30 years and the analysis was conducted from an English National Health Service (NHS) and Personal Social Services perspective. A probabilistic sensitivity analysis was performed to account for uncertainties in the model parameters.Main outcome measuresOutcomes for the entire simulated period included the following: total costs for PROMPT or shoulder dystocia training (including costs of OBPIs), number of OBPIs averted, number of affected adult/parental/dyadic quality adjusted life years (QALYs) gained and the incremental cost per QALY gained.ResultsNationwide PROMPT or shoulder dystocia training conferred significant savings (in excess of £1 billion ($1.5 billion)) compared to current practice, resulting in cost-savings of at least £1 million ($1.5 million) per any type of QALY gained. The probabilistic sensitivity analysis demonstrated similar findings.ConclusionIn this model, national implementation of multi-professional simulation training for obstetric emergencies (or standalone shoulder dystocia training) in England appeared to both be cost-saving when evaluating their impact on permanent OBPIs

Compact, modular and in-plane AOSLO for high-resolution retinal imaging

The adaptive optics scanning laser ophthalmoscope (AOSLO) was first developed in 2002 and since then the technology has been adopted in several laboratories around the world, for both clinical and psychophysical research. There have been a few major design implementations of the AOSLO. The first used on-axis tilted spherical mirrors in a planar arrangement, and the second minimized the build up of astigmatism present in the first design by using a non-planar arrangement. Other designs have avoided astigmatism by using custom-made toroidal mirrors or by using lenses on-axis, rather than mirrors. We present a new design implementation for an AOSLO that maintains a planar optical alignment without the build up astigmatism using compact, reconfigurable modules based on an Offner relay system. We additionally use an off-the-shelf digital oscilloscope for data capture and custom-written Python code for generating and analyzing the retinal images. This design results in a compact system that is simple to align and, being composed of modular relays, has the potential for additional components to be added. We show that this system maintains diffraction-limited image quality across the field of view and that cones are clearly resolved in the central retina. The modular relay design is generally applicable to any system requiring one or more components in the pupil conjugate plane. This is likely to be useful for any point-scanned system, such as a standard scanning laser ophthalmoscope or non-ophthalmic confocal imaging system