The UK Clinical Research Collaboration (UKCRC) Tissue Directory and Coordination Centre: the UK’s centre for facilitating the usage of human samples for medical research

The UKCRC Tissue Directory and Coordination Centre was established to improve access to and utilisation of UK human tissue samples for medical research. The key output of the Centre is the creation of the UK’s first pan-disease Tissue Directory (https://directory.biobankinguk.org/). Any researcher can search the Directory based on a series of simple key words including disease classification, age, sex, sample type, preservation details, quality indicators and datasets available. The Directory as of April 2017 contains 100 Bioresources. Researchers seeking fresh samples can also search for facilities that offer bespoke collection services. Future work of the Centre will be to explore greater standardisation of biobanking activities across the UK and to facilitate an inter-connected research infrastructure related to the use of human biosamples

Transformação de algodão (Gossypium Hirsutum L.) através do uso de policátion.

bitstream/CNPA/21492/1/CIRTEC81.pd

Fourier Method for Approximating Eigenvalues of Indefinite Stekloff Operator

We introduce an efficient method for computing the Stekloff eigenvalues associated with the Helmholtz equation. In general, this eigenvalue problem requires solving the Helmholtz equation with Dirichlet and/or Neumann boundary condition repeatedly. We propose solving the related constant coefficient Helmholtz equation with Fast Fourier Transform (FFT) based on carefully designed extensions and restrictions of the equation. The proposed Fourier method, combined with proper eigensolver, results in an efficient and clear approach for computing the Stekloff eigenvalues.Comment: 12 pages, 4 figure

Importance of single or blended polymer types for controlled in vitro release and plasma levels of a somatostatin analogue entrapped in PLA/PLGA microspheres.

The aim of the work was to develop biodegradable microspheres for controlled delivery of the somatostatin analogue vapreotide and maintenance of sustained plasma levels over 2–4 weeks after a single injection in rats. Vapreotide was microencapsulated into end-group capped and uncapped low molecular weight poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) by spray-drying and coacervation. Microspheres were prepared from single and blended (1:1) polymer types. The microparticles were characterized for peptide loading, in vitro release and pharmocokinetics in rats. Spray-drying and coacervation produced microspheres in the size range of 1–15 and 10–70 μm, respectively, and with encapsulation efficiencies varying between 46% and 87%. In vitro release of vapreotide followed a regular pattern and lasted more than 4 weeks, time at which 40–80% of the total dose were released. Microspheres made of 14-kDa end-group uncapped PLGA50:50 or 1:1 blends of this polymer with 35 kDa end-group uncapped PLGA50:50 gave the best release profiles and yielded the most sustained plasma levels above a pre-defined 1 ng/ml over approximately 14 days. In vitro/in vivo correlation analyses showed for several microsphere formulations a linear correlation between the mean residence time in vivo and the mean dissolution time (r=0.958) and also between the amount released between 6 h and 14 days and the AUC6h–14d (r=0.932). For several other parameters or time periods, no in vitro/in vivo correlation was found. This study demonstrates that controlled release of the vapreotide is possible in vivo for a duration of a least 2 weeks when administered i.m. to rats. These results constitute a step forward towards a twice-a-month or once-a-month microsphere-formulation for the treatment of acromegaly and neuroendocrine tumors

In vitro cell compatibility and antibacterial activity of microencapsulated doxycycline designed for improved localized therapy of septic arthritis

OBJECTIVES: For the treatment of septic arthritis in large animals, the local application of antibiotics as a slow release system may be an appropriate means to reach high local bioactivity and low systemic side effects and drug residues. In this study, doxycycline microspheres were developed and tested in vitro for their drug-release properties, suitability for intra-articular application and antimicrobial activity. METHODS: The development of a slow release system was achieved by microencapsulation of the drug into poly(lactide-co-glycolide) microspheres by a novel ultrasonic atomization method. Drug elution was evaluated from microspheres dispersed in elution medium at pre-defined time points by HPLC. Joint-tissue compatibility was tested on cultured bovine synoviocytes by evaluating the expression of pro-inflammatory cytokine mRNA and the production of nitric oxide (NO). Finally, the antimicrobial activity of the released antibiotic was assessed with gram-negative and gram-positive bacteria exposed to release medium sampled at days 1, 7 and 12 after microsphere suspension. RESULTS: An adequate size of the microspheres, sufficient stabilization of doxycycline in aqueous environment and drug release (25 mg microspheres in 4 mL medium) above MIC for bacteria usually isolated in bovine and equine joints were obtained over 15 days. Although the cytokine mRNA expression reflected the excellent tissue compatibility, the results with NO yielded contradictory results. Antimicrobial tests of the release medium proved to match perfectly the activity of non-encapsulated, free doxycycline as reported in the literature. CONCLUSIONS: The newly developed doxycycline delivery system achieved the target specifications and is ready for in vivo testin

Gentamicin-loaded microspheres for reducing the intracellular Brucella abortus load in infected monocytes

Objectives: The intracellular antibiotic efficiency of gentamicin-loaded microspheres in the context of Brucella-infected murine monocytes was examined in vitro with a view to developing improved therapies for the treatment of brucellosis. Methods: Biodegradable microspheres made of end-group capped and uncapped poly(lactide-co-glycolide) 50:50 (PLGA 50:50 and PLGA 50:50H) and containing gentamicin sulphate were used to target Brucella abortus-infected J774 monocyte-macrophages. The infected cells were treated with 15 µg of free or microencapsulated gentamicin and the efficacy of the treatments was measured after 24 h. Results: The particle sizes were below 8 µm and in vitro release of gentamicin from the microspheres followed a continuous (PLGA 50:50H) or a multiphasic (PLGA 50:50) pattern over 50 days. Treatment with gentamicin microencapsulated into the end-group uncapped PLGA 50:50H microspheres, decreased significantly the number of intracellular bacteria (typically by 2 log10) in comparison with untreated infected cells. Addition of 2% poloxamer 188 to the microsphere dispersion medium further reduced the infection (3.5 log10). Opsonization of the particles with non-immune mouse serum had no effect on the antibacterial efficacy of the microspheres. End-group capped PLGA 50:50 type microspheres containing the antibiotic were less effective at reducing intracellular bacteria (∼1 log10 reduction), although addition of poloxamer 188 to the dispersion medium again enhanced their intracellular antibacterial activity. Placebo PLGA 50:50 and PLGA 50:50H microspheres had no bactericidal activity. Conclusions: The results indicate that PLGA 50:50-microencapsulated gentamicin sulphate may be suitable for efficient drug targeting and delivery to reduce intracellular Brucella infections

Fast interior point solution of quadratic programming problems arising from PDE-constrained optimization

Interior point methods provide an attractive class of approaches for solving linear, quadratic and nonlinear programming problems, due to their excellent efficiency and wide applicability. In this paper, we consider PDE-constrained optimization problems with bound constraints on the state and control variables, and their representation on the discrete level as quadratic programming problems. To tackle complex problems and achieve high accuracy in the solution, one is required to solve matrix systems of huge scale resulting from Newton iteration, and hence fast and robust methods for these systems are required. We present preconditioned iterative techniques for solving a number of these problems using Krylov subspace methods, considering in what circumstances one may predict rapid convergence of the solvers in theory, as well as the solutions observed from practical computations

Mining and analysis of audiology data to find significant factors associated with tinnitus masker

Objectives: The objective of this research is to find the factors associated with tinnitus masker from the literature, and by using the large amount of audiology data available from a large NHS (National Health Services, UK) hearing aid clinic. The factors evaluated were hearing impairment, age, gender, hearing aid type, mould and clinical comments. Design: The research includes literature survey for factors associated with tinnitus masker, and performs the analysis of audiology data using statistical and data mining techniques. Setting: This research uses a large audiology data but it also faced the problem of limited data for tinnitus. Participants: It uses 1,316 records for tinnitus and other diagnoses, and 10,437 records of clinical comments from a hearing aid clinic. Primary and secondary outcome measures: The research is looking for variables associated with tinnitus masker, and in future, these variables can be combined into a single model to develop a decision support system to predict about tinnitus masker for a patient. Results: The results demonstrated that tinnitus maskers are more likely to be fit to individuals with milder forms of hearing loss, and the factors age, gender, type of hearing aid and mould were all found significantly associated with tinnitus masker. In particular, those patients having Age<=55 years were more likely to wear a tinnitus masker, as well as those with milder forms of hearing loss. ITE (in the ear) hearing aids were also found associated with tinnitus masker. A feedback on the results of association of mould with tinnitus masker from a professional audiologist of a large NHS (National Health Services, UK) was also taken to better understand them. The results were obtained with different accuracy for different techniques. For example, the chi-squared test results were obtained with 95% accuracy, for Support and Confidence only those results were retained which had more than 1% Support and 80% Confidence. Conclusions: The variables audiograms, age, gender, hearing aid type and mould were found associated with the choice of tinnitus masker in the literature and by using statistical and data mining techniques. The further work in this research would lead to the development of a decision support system for tinnitus masker with an explanation that how that decision was obtained

In vitro and in vivo evaluation of a somatostatin analogue released from PLGA microspheres

The purpose of this study was to design poly(lactide-co-glycolide) (PLGA) microspheres for the continuous delivery of the somatostatin analogue, vapreotide, over 2–4 weeks. The microspheres were produced by spray-drying and the desired characteristics, i.e. high encapsulation efficiency and controlled release over 2–4 weeks, achieved through optimizing the type of polymer, processing solvent, and co-encapsulated additive. The in vitro release was tested in fetal bovine serum preserved with 0.02% of thiomersal. Furthermore, formulations were injected intramuscularly into rats to obtain pharmacokinetic profiles. Encapsulation efficiency was between 34 and 91%, depending on the particular formulation. The initial peptide release (within 6 h) was lowest, i.e. 1 ng/ml) over 21–28 days in rats was the one made with end-group uncapped PLGA 50:50, the solvent acetic acid and the additive polyethyleneglycol. In conclusion, the optimization of formulation parameters allowed us to produce vapreotide-loaded PLGA microspheres of suitable characteristics for therapeutic use

Euclidean Structure from N>=2 Parallel Circles: Theory and Algorithms

International audienceOur problem is that of recovering, in one view, the 2D Euclidean structure, induced by the projections of N parallel circles. This structure is a prerequisite for camera calibration and pose computation. Until now, no general method has been described for N > 2. The main contribution of this work is to state the problem in terms of a system of linear equations to solve.We give a closed-form solution as well as bundle adjustment-like refinements, increasing the technical applicability and numerical stability. Our theoretical approach generalizes and extends all those described in existing works for N = 2 in several respects, as we can treat simultaneously pairs of orthogonal lines and pairs of circles within a unified framework. The proposed algorithm may be easily implemented, using well-known numerical algorithms. Its performance is illustrated by simulations and experiments with real images