Three venepuncture techniques in babies: a comparative study

Modifying hyodermic needles for blood sampling in babies is common. However, such techniques mean that medical devices are not always used as manufacturers intend and potential and actual risks associated with their use occur. A number of new devices have recently been designed to overcome safety issues. However, whether new devices are any more effective than existing modified methods is unknown. Through a randomoised controlled trial, this study attempted to compare the safety and efficacy of three blood sampling techniques in babies: (i) the 'broken' needle, (ii) the 'modified' buttrefly' and (iii) a new 'single winged' needle designed specifically for venepuncture in babies and young children. Eligibility criteria for inclusion to the study comprised: babies twelve months of age and under, weighing over 1500 grams, requiring at least three routine blood samples to monitor their condition, six hours apart. Informed, written parental consent was also required. The sample was drawn from a neonatal intensive care unit and achildren's unit in a large teaching hospital. Ethical approval for the study was gained form the local research ethics committee. Babies recruited into the study were randomised according to the order in which the three blood sampling techniques were used. Data were collected in terms of: (1) whether the blood sample had been obtained after one, two or more than two attempts; (2) whether there was clotting in the sample and (3) whether there was bruising and the extent of the bruising measured at the largest diamter of the bruise. Fourteen babies completed the study reulting in the trail being severely underpowered. Recruitment to the study was disappointing and was, in part, attributed to a number of adverse incidents that had occurred in clinical and research practices involving babies and children, that had gained much media attention, both before and during the study period

The synthesis of tetrafluorinated aminosugars

The synthesis of two tetrafluorinated 4-aminosugars, 4-amino-2,3,4-trideoxy-2,2,3,3-tetrafluoro-d-erythro-hexopyranose hydrochloride (7•HCl) and 4-amino-2,3,4-trideoxy-2,2,3,3-tetrafluoro-d-threo-hexopyranose hydrochloride (8•HCl), is described. The amino group in ?-position of a CF2(CF2) group is proposed as a mimic for the hydrogen bond accepting capacity of an alcohol group in an unfluorinated sugar. The synthesis of the two sugars was achieved in 4 steps each from the sulfinylimine diastereoisomers of d-glyceraldehyde

N1-arylation of 1,4-benzodiazepine-2-ones with diaryliodonium salts

A library of N1-arylated 5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-ones has been synthesized starting with unsymmetrical diaryliodonium salts using aqueous ammonia as a base. This can also be applied to a similar 1,3,4-benzotriazepin-2-one derivative

Improving the forward model for electrical impedance tomography of brain function through rapid generation of subject specific finite element models

Electrical Impedance Tomography (EIT) is a non-invasive imaging method which allows internal electrical impedance of any conductive object to be imaged by means of current injection and surface voltage measurements through an array of externally applied electrodes. The successful generation of the image requires the simulation of the current injection patterns on either an analytical or a numerical model of the domain under examination, known as the forward model, and using the resulting voltage data in the inverse solution from which images of conductivity changes can be constructed. Recent research strongly indicates that geometric and anatomical conformance of the forward model to the subject under investigation significantly affects the quality of the images. This thesis focuses mainly on EIT of brain function and describes a novel approach for the rapid generation of patient or subject specific finite element models for use as the forward model. After introduction of the topic, methods of generating accurate finite element (FE) models using commercially available Computer-Aided Design (CAD) tools are described and show that such methods, though effective and successful, are inappropriate for time critical clinical use. The feasibility of warping or morphing a finite element mesh as a means of reducing the lead time for model generation is then presented and demonstrated. This leads on to the description of methods of acquiring and utilising known system geometry, namely the positions of electrodes and registration landmarks, to construct an accurate surface of the subject, the results of which are successfully validated. The outcome of this procedure is then used to specify boundary conditions to a mesh warping algorithm based on elastic deformation using well-established continuum mechanics procedures. The algorithm is applied to a range of source models to empirically establish optimum values for the parameters defining the problem which can successfully generate meshes of acceptable quality in terms of discretization errors and which more accurately define the geometry of the target subject. Further validation of the algorithm is performed by comparison of boundary voltages and image reconstructions from simulated and laboratory data to demonstrate that benefits in terms of image artefact reduction and localisation of conductivity changes can be gained. The processes described in the thesis are evaluated and discussed and topics of further work and application are described

Synergistic effects of inhibiting the MNK-eIF4E and PI3K/AKT/mTOR pathways on cell migration in MDA-MB-231 cells

The study of eukaryotic initiation factor 4E (eIF4E) is a key focus in cancer research due to its role in controlling the translation of tumour-associated proteins, that drive an aggressive migratory phenotype. eIF4E is a limiting component of the eIF4F complex which is a critical determinant for the translation of mRNAs. Mitogenactivated protein kinase interacting protein kinases (MNK1/2) phosphorylate eIF4E on Ser209, promoting the expression of oncogenic proteins, whereas mTORC1 phosphorylates and de-activates the eIF4E inhibitor, 4E-BP1, to release translational repression. Here we show that inhibiting these pathways simultaneously effectively slows the rate of cell migration in breast cancer cells. However, a molecular hybridisation approach using novel, cleavable dual MNK1/2 and PI3K/mTOR inhibiting hybrid agents was less effective at slowing cell migration

Synthesis and reactivity of N-allenyl cyanamides

N-Allenyl cyanamides have been accessed via a one-pot deoxycyanamidation–isomerization approach using propargyl alcohol and N-cyano-N-phenyl-p-methylbenzenesulfonamide. The utility of this novel class of allenamide was explored through derivatization, with hydroarylation, hydroamination, and cycloaddition protocols employed to access an array of cyanamide products that would be challenging to access using existing methods

Copper(II)-benzotriazole coordination compounds in click chemistry: a diagnostic reactivity study

This diagnostic study aims to shed light on the catalytic activity of a library of Cu(II) based coordination compounds with benzotriazole-based ligands. We report herein the synthesis and characterization of five new coordination compounds formulated [CuII(L4)(MeCN)2(CF3SO3)2] (1), [CuII(L5)2(CF3SO3)2] (2), [CuII(L6)2(MeCN)(CF3SO3)]·(CF3SO3) (3), [CuII(L6)2(H2O)(CF3SO3)]·(CF3SO3)·2(Me2CO) (4), [CuI4(L1)2(L1’)2(CF3SO3)2]2·4(CF3SO3)·8(Me2CO) (5), derived from similar nitrogen-based ligands. The homogeneous catalytic activity of these compounds along with our previously reported coordination compounds (6 -13), derived from similar ligands, is tested against the well-known Cu(I)-catalysed azide-alkyne cycloaddition reaction. The optimal catalyst [CuII(L1)2(CF3SO3)2] (10) activates the reaction to afford 1,4-disubstituted 1,2,3-triazoles with yields up to 98% and without requiring a reducing agent. Various control experiments are performed to optimize the method as well as examine parameters such as ligand variation, metal coordination geometry and environment, in order to elucidate the behaviour of the catalytic system

Rapid generation of subject-specific thorax forward models

For real-time monitoring of lung function using accurate patient geometry, shape information needs to be acquired and a forward model generated rapidly. This paper shows that warping a cylindrical model to an acquired shape results in meshes of acceptable mesh quality, in terms of stretch and aspect ratio