Optimization of Optical and Mechanical Properties of Real Architecture for 3-Dimensional Tissue Equivalents: Towards Treatment of Limbal Epithelial Stem Cell Deficiency

Limbal epithelial stem cell (LESC) deficiency can cause blindness. Transplantation of cultured human limbal epithelial cells (hLE) on human amniotic membrane (HAM) can restore vision but clinical graft manufacture can be unreliable. We have developed a reliable and robust tissue equivalent (TE) alternative to HAM, Real Architecture for 3D Tissue (RAFT). Here, we aimed to optimize the optical and mechanical properties of RAFT TE for treatment of LESC deficiency in clinical application. The RAFT TE protocol is tunable; varying collagen concentration and volume produces differing RAFT TEs. These were compared with HAM samples taken from locations proximal and distal to the placental disc. Outcomes assessed were transparency, thickness, light transmission, tensile strength, ease of handling, degradation rates and suitability as substrate for hLE culture. Proximal HAM samples were thicker and stronger with poorer optical properties than distal HAM samples. RAFT TEs produced using higher amounts of collagen were thicker and stronger with poorer optical properties than those produced using lower amounts of collagen. The ‘optimal’ RAFT TE was thin, transparent but still handleable and was produced using 0.6 ml of 3 mg/ml collagen. Degradation rates of the ‘optimal’ RAFT TE and HAM were similar. hLE achieved confluency on ‘optimal’ RAFT TEs at comparable rates to HAM and cells expressed high levels of putative stem cell marker p63α. These findings support the use of RAFT TE for hLE transplantation towards treatment of LESC deficiency

Islands of conformational stability for Filopodia

Filopodia are long, thin protrusions formed when bundles of fibers grow outwardly from a cell surface while remaining closed in a membrane tube. We study the subtle issue of the mechanical stability of such filopodia and how this depends on the deformation of the membrane that arises when the fiber bundle adopts a helical configuration. We calculate the ground state conformation of such filopodia, taking into account the steric interaction between the membrane and the enclosed semiflexible fiber bundle. For typical filopodia we find that a minimum number of fibers is required for filopodium stability. Our calculation elucidates how experimentally observed filopodia can obviate the classical Euler buckling condition and remain stable up to several tens of . We briefly discuss how experimental observation of the results obtained in this work for the helical-like deformations of enclosing membrane tubes in filopodia could possibly be observed in the acrosomal reactions of the sea cucumber Thyone, and the horseshoe crab Limulus. Any realistic future theories for filopodium stability are likely to rely on an accurate treatment of such steric effects, as analysed in this work

System and market failures: the unavailability of magnesium sulphate for the treatment of eclampsia and pre-eclampsia in Mozambique and Zimbabwe.

Low cost and effective drugs, such as magnesium sulphate, need to be included in initiatives to improve access to essential medicines in Afric

Semiflexible polymers: Dependence on ensemble and boundary orientations

We show that the mechanical properties of a worm-like-chain (WLC) polymer, of contour length $L$ and persistence length \l such that t=L/\l\sim{\cal O}(1), depend both on the ensemble and the constraint on end-orientations. In the Helmholtz ensemble, multiple minima in free energy near $t=4$ persists for all kinds of orientational boundary conditions. The qualitative features of projected probability distribution of end to end vector depend crucially on the embedding dimensions. A mapping of the WLC model, to a quantum particle moving on the surface of an unit sphere, is used to obtain the statistical and mechanical properties of the polymer under various boundary conditions and ensembles. The results show excellent agreement with Monte-Carlo simulations.Comment: 15 pages, 15 figures; version accepted for publication in Phys. Rev. E; one new figure and discussions adde

The provision of education and training for healthcare professionals through the medium of the internet

This paper describes a new initiative to provide Internet based courses to student and professional occupational therapists in four centres in the UK, Belgium the Netherlands and Sweden. The basis of this collaborative Occupational Therapy Internet School (OTIS) is the concept of the “Virtual College”. This comprises the design and implementation of a sophisticated Internet-based system through which courses can be managed, prepared and delivered online in an effective fashion, and where students can communicate both with the staff and their peers. The aim is to support and facilitate the whole range of educational activities within a remote electronic environment. A major feature of the course organisation is the adoption of a problem-based approach in which students will collaborate internationally to propose effective intervention in given case study scenarios. The paper outlines the rationale for OTIS, the content and structure of the courseware, the technical specification of the system and evaluation criteria. In addition to the more conventional web-based learning facilities generally offered, a number of agent-based approaches are being adopted to assist in the management of the course by ensuring the proper delivery of course materials and to assist the functioning of project groups. </p

The Suitability of Discharge Information for Parents of Infants with Single Functioning Ventricle Heart Condition: Evolution of a Congenital Heart Assessment Tool (CHAT) for Parents

Whilst advances in the care of infants with complex congenital heart disease (CHD) have resulted in remarkably improved prognosis, death between first and second surgical stage has remained a concern in the UK and America particularly for those with single cardiac ventricle anatomy.1-8 This has prompted the development of home monitoring programs (HMP) to encourage early identification at home, of infants vulnerable to potentially life threatening events4, 5 ,9-13. However to date no randomised controlled trials have been published and therefore the robustness of the available research is debatable. In 2011 a research proposal was developed by KG (Coventry University) in collaboration with the team at Birmingham Children’s Hospital and Little Hearts Matter (LHM) to undertake a Feasibility Study (randomised controlled trial) to test the feasibility of using a Congenital Heart Assessment Tool (CHAT) as part of a home monitoring programme (HMP) for infants with single ventricle heart conditions and those with systemic shunt dependent heart conditions. A consultation event [funded by a Patient and Public Involvement (PPI) Bursary from the NIHR West Midlands Research Design Service ]was hosted by LHM in September 2011 during which a Focus Group was facilitated by KG with a small group of parents to ascertain their views regarding the implementation of a home monitoring programme. The Focus Group was transcribed, thematically analysed and subsequently contributed to the development of the content of the online survey and the Congenital Heart Assessment Tool (CHAT) which is being reported in this poster presentation

Segregation by thermal diffusion in granular shear flows

Segregation by thermal diffusion of an intruder immersed in a sheared granular gas is analyzed from the (inelastic) Boltzmann equation. Segregation is induced by the presence of a temperature gradient orthogonal to the shear flow plane and parallel to gravity. We show that, like in analogous systems without shear, the segregation criterion yields a transition between upwards segregation and downwards segregation. The form of the phase diagrams is illustrated in detail showing that they depend sensitively on the value of gravity relative to the thermal gradient. Two specific situations are considered: i) absence of gravity, and ii) homogeneous temperature. We find that both mechanisms (upwards and downwards segregation) are stronger and more clearly separated when compared with segregation criteria in systems without shear.Comment: 8 figures. To appear in J. Stat. Mec

Evaluation of the efficacy and safety of high dose short duration enrofloxacin treatment regimen for uncomplicated urinary tract infections in dogs.

BackgroundUncomplicated urinary tract infections (UTI) in dogs usually are treated with antimicrobial drugs for 10-14 days. Shorter duration antimicrobial regimens have been evaluated in human patients.HypothesisA high dose short duration (HDSD) enrofloxacin protocol administered to dogs with uncomplicated UTI will not be inferior to a 14-day treatment regimen with amoxicillin-clavulanic acid.AnimalsClient-owned adult, otherwise healthy dogs with aerobic bacterial urine culture yielding ≥ 10(3) CFU/mL of bacteria after cystocentesis.MethodsProspective, multicenter, controlled, randomized blinded clinical trial. Enrolled dogs were randomized to group 1 (enrofloxacin 18-20 mg/kg PO q24h for 3 days) or group 2 (amoxicillin-clavulanic acid 13.75-25 mg/kg PO q12h for 14 days). Urine cultures were obtained at days 0, 10, and 21. Microbiologic and clinical cure rates were evaluated 7 days after antimicrobial treatment was discontinued. Lower urinary tract signs and adverse events also were recorded.ResultsThere were 35 dogs in group 1 and 33 in group 2. The microbiologic cure rate was 77.1 and 81.2% for groups 1 and 2, respectively. The clinical cure rate was 88.6 and 87.9% for groups 1 and 2, respectively. Cure rates between groups did not differ according to the selected margin of noninferiority.Conclusions and clinical importanceHDSD enrofloxacin treatment was not inferior to a conventional amoxicillin-clavulanic acid protocol for the treatment of uncomplicated bacterial UTI in dogs. Further research is warranted to determine if this protocol will positively impact owner compliance and decrease the emergence of antimicrobial resistance