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PubMed2005

The birth of the e-clinic. Continuity or transformation in the UK governance of pharmaceutical consumption?

Traditional arrangements for the prescription and dispensing of pharmaceuticals have been challenged by the rise of Internet services enabling consumers to acquire these products online, without a face-to-face contact with a professional. This paper considers three moments in the emergence of the 'e-clinic' as an alternative route to prescription drugs in the United Kingdom: the electronic transfer of prescriptions; the development of the e-pharmacy and the 'virtual' pharmacist, and the establishment of online virtue medicine consultations. We examine the phenomenon in relation to issues of governance, considering the legal and voluntary frameworks that govern prescribing. Documentary and interview data suggest that the Internet has the potential to transform the relations between prescribers, dispensers and consumers, but that stakeholders seek continuity by applying existing governance frameworks and codes of conduct. This continuity can be explained by Rosenau's (Along the Domestic-Foreign Frontier. Cambridge University Press, Cambridge, 1997) model of a contested and fragmenting process of technology governance.

Diffusion of Innovation↗
PubMed2001

[Study of continuous wavelet transform on detecting and enhancing blood vessel in DSA image].

Low contrast is the shortcoming of the image in Digital Subtraction Angiography. This paper presents a new approach for the enhancement of blood volume in DSA image. The wavelet transform was applied to detect blood edges, and then the image contrast was enhanced by the method of contrast stretched. Because the continuous wavelet adopted in this study can detect gray variety in different orientations, the blood vessel edge detected by this algorithm is more precise and complete. Moreover, because the module of image noise by wavelet transform is smaller, the algorithm can protrude blood vessel but restrain noise in background. The processing result showed a very good optical effect of 3 dimensional objects for medical diagnoses.

Angiography, Digital Subtraction↗
PubMed1998

Definition of a four-dimensional continuous planispheric transformation for the tracking and the analysis of left-ventricle motion.

Cardiologists assume that analysis of the motion of the heart (especially the left ventricle) can provide useful information about the health of the myocardium. A 4-D polar transformation is defined to describe the left-ventricle (LV) motion and a method is presented to estimate it from sequences of 3-D images. The transformation is defined in 3-D planispheric coordinates (3PC) by a small number of parameters involved in a set of simple linear equations. It is continuous and regular in time and space, and periodicity in time can be imposed. The local motion can be easily decomposed into a few canonical motions (radial motion, rotation around the long-axis, elevation). To recover the motion from original data, the 4-D polar transformation is calculated using an adaptation of the iterative closest-point algorithm. We present the mathematical framework and a demonstration of its feasability on a series of gated SPECT sequences.

Humans↗
PubMed2000

Continuous enzymatic transformation in an enzyme membrane reactor with simultaneous NAD(H) regeneration. Reprinted from Biotechnology and Bioengineering, Vol. XXIII, No. 12, Pages 2789-2802 (1981).

Multienzyme reaction systems with simultaneous coenzyme regeneration have been investigated in a continuously operated membrane reactor at bench scale. NAD(H) covalently bound to polyethylene glycol with a molecular weight of 10(4) [PEG-10,000-NAD(H)] was used as coenzyme. It could be retained in the membrane reactor together with the enzymes. L-leucine dehydrogenase (LEUDH) was used as catalyst for the reductive amination of alpha-ketoisocaproate (2-oxo-4-methylpentanoic acid) to L-leucine. Formate dehydrogenase (FDH) was used for the regeneration of NADH. Kinetic experiments were carried out to obtain data which could be used in a kinetic model in order to predict the performance of an enzyme membrane reactor for the continuous production of L-leucine. The kinetic constants V(max) and k(m) of the enzymes are all in the same range regardless of whether native NAD(H) or PEG-10,000-NAD(H) is used as coenzyme. L-leucine was produced continuously out of alpha-ketoisocaproate for 48 days; a maximal conversion of 99.7% was reached. The space-time yield was 324 mmol/L day (or 42.5 g/L day).

Bioreactors↗
PubMed1987

Enhancement of transformation and continuous inhibition of intercellular communication by 1-oleoyl-2-acetyl glycerol in BALB/c 3T3 cells.

Tumour-promoting phorbol esters and diacylglycerols have a variety of biochemical and biological effects in common in a number of cell culture systems; thus, it has been suggested that diacylglycerols are endogenous functional analogues of phorbol esters. In order to examine more directly the possible relevance of these functional analogues in tumour promotion, we have studied the promoting effect of 1-oleoyl-2-acetyl glycerol (OAG) in the two-stage transformation model with BALB/c 3T3 cells, which is designed to simulate in vivo two-stage carcinogenesis. When BALB/c 3T3 cells were treated once with a low dose of 3-methylcholanthrene (MCA), almost no increase in cell transformation occurred. However, repeated application of OAG after MCA treatment enhanced cell transformation. OAG enhanced transformation to a lesser extent than a potent promoter of in vivo and in vitro carcinogenesis, phorbol-12,13-didecanoate. OAG also continuously inhibited junctional intercellular communication when BALB/c 3T3 cells were treated daily at confluence. These results indicate that diacylglycerols mimic phorbol esters in promoting cell transformation and that the enhancement may be related to an inhibitory effect on intercellular communication.

Animals↗
PubMed2006

Microwave-assisted Suzuki coupling reactions with an encapsulated palladium catalyst for batch and continuous-flow transformations.

This article describes the design, optimisation and development of a Suzuki cross-coupling protocol mediated by an efficient palladium-encapsulated catalyst (Pd EnCat) under microwave irradiation. The methodology has been used in both batch mode for classical library preparation and in continuous-flow applications furnishing multigram quantities of material. Described is a method that uses direct focused microwave heating whilst applying an external cooling source. This enables a lower than normal bulk temperature to be maintained throughout the reaction period leading to significant improvements in the overall yield and purity of the reaction products. Additional aspects of this novel heating protocol are discussed in relation to the prolonged lifetime and enhanced reactivity of the immobilised catalyst system.

Catalysis↗
PubMed1995

The loss of contact inhibition and anchorage-dependent growth are key steps in the acquisition of Listeria monocytogenes susceptibility phenotype by non-phagocytic cells.

We have previously demonstrated that intestinal and kidney finite cell lines were resistant to L monocytogenes invasion (ie allowed low bacterial entry and no intracellular multiplication) in contrast to the continuous cell lines which were susceptible to Listeria invasion (ie allowed high bacterial entry and intracellular multiplication) (Velge et al (1994a) Med Microbial Immunol 183, 145). The aim of this study was to discover whether epigenetic or genetic cellular modifications could convert L monocytogenes resistant cells into a susceptible phenotype and to determine the cellular steps involved in Listeria susceptibility. Among the 5-azacytidine treated finite cell lines, the untransformed immortal cell lines established remained resistant to L monocytogenes invasion whereas the weakly transformed continuous cell lines established were converted into a susceptible phenotype. Transfection of resistant cells by SV40 large T antigen induced only highly transformed continuous cell lines displaying a susceptible phenotype. Taken together these data show that cell transformation enhanced Listeria invasion. This conclusion was supported by the observation that L monocytogenes was able to induce cell foci within murine finite cell monolayers. This morphological cell transformation was completely reversible and required live bacteria inside cells. In conclusion, we may speculate that the L monocytogenes intracellular multiplication observed within cell foci could be explained by the loss of contact inhibition of the finite cell monolayer. Indeed, the loss of both contact inhibition and anchorage-dependent growth are the key steps involved in the L monocytogenes susceptibility phenotype.

Animals↗
PubMed2006

Spatial vs temporal continuity in view invariant visual object recognition learning.

We show in a 4-layer competitive neuronal network that continuous transformation learning, which uses spatial correlations and a purely associative (Hebbian) synaptic modification rule, can build view invariant representations of complex 3D objects. This occurs even when views of the different objects are interleaved, a condition where temporal trace learning fails. Human psychophysical experiments showed that view invariant object learning can occur when spatial but not temporal continuity applies because of interleaving of stimuli, although sequential presentation, which produces temporal continuity, can facilitate learning. Thus continuous transformation learning is an important principle that may contribute to view invariant object recognition.

Computer Simulation↗
PubMed1989

Transformation to continuous growth of primary human T lymphocytes by human T-cell leukemia virus type I X-region genes transduced by a Herpesvirus saimiri vector.

The role of the X region of the genome of the human T-cell leukemia virus type I (HTLV-I) in the immortalization of lymphocytes has been difficult to distinguish from its role in viral replication as this region encodes at least two genes, tax and rex, required for replication and the expression of viral proteins. To determine whether the X region does encode immortalizing functions, a fragment of the HTLV-I provirus capable of expressing known X-region proteins was inserted into the genome of a transformation-defective, replication-competent Herpesvirus saimiri. Infection of fresh mitogen-activated human cord blood and thymocytes yielded immortal T-cell lines that had the same phenotype (CD4+, CD5+, HLA class II+, interleukin 2 receptor alpha-chain +) as lymphocytes transformed by cocultivation with HTLV-I. These experiments demonstrate that the X region encodes the functions of HTLV-I that immortalize a distinct subpopulation of human T cells. The experiments also demonstrate the utility of the H. saimiri vector for the transduction of heterologous genes into human T cells.

Cell Transformation, Neoplastic↗
PubMed2005

Density functional theory study of the nematic-isotropic transition in an hybrid cell.

We have employed the density functional theory formalism to investigate the nematic-isotropic capillary transitions of a nematogen confined by walls that favor antagonist orientations to the liquid crystal molecules (hybrid cell). We analyze the behavior of the capillary transition as a function of the fluid-substrate interactions and the pore width. In addition to the usual capillary transition between isotropiclike to nematiclike states, we find that this transition can be suppressed when one substrate is wet by the isotropic phase and the other by the nematic phase. Under this condition the system presents interfacelike states which allow us to continuously transform the nematiclike phase to the isotropiclike phase without undergoing a sharp phase transition. Two different mechanisms for the disappearance of the capillary transition are identified. When the director of the nematiclike state is homogeneously planar-anchored with respect to the substrates, the capillary transition ends up in a critical point. This scenario is analogous to the observed in Ising models when confined in slit pores with opposing surface fields which have critical wetting transitions. When the nematiclike state has a linearly distorted director field, the capillary transition continuously transforms in a transition between two nematiclike states.

Journal Article↗
PubMed2005

Digital cushions in horses comprise coarse connective tissue, myxoid tissue, and cartilage but only little unilocular fat tissue.

Digital cushions were studied in horses with particular reference to vascularization, tissue constituents and matrix components. The cushions mainly resembled a network of coarse collagen bundles. The areas inbetween the bundles were replenished with loosely woven interstitial connective tissue, myxoid tissue, and fibrocartilage. Expected masses of fat lobules were missing: only solitary adipocytes or small groups of adipocytes were seen. Vascular supply to the cushions was remarkably poor. The mucinous myxoid matrix largely consisted of hyaluronan with little sulphated glycosaminoglycans. Myxoid cells were stellate or ramified in shape and showed a tendency to store glycogen and lipid droplets. Myxoid cells reacted for vimentin and stained for S-100 protein. Moreover, myxoid cells often reacted for neuron specific enolase and glial fibrillary acidic protein. Myxoid tissue continuously transformed into loosely organized interstitial connective tissue with fibroblasts, which remained unreactive when tested for neuroectodermal markers. Myxoid tissue also was not clearly demarcated against irregularly interspersed islets of fibrocartilage or hyaline cartilage. Chondrocytes did not stain for neuron specific enolase but reactivity for S-100 protein and glial fibrillary acidic protein was noted in peripheral regions of fibrocartilage. Single or grouped unilocular fat cells were rarely placed into myxoid areas. Unilocular fat cells stained for vimentin, S-100 protein, and occasionally for glial fibrillary acidic protein but not for neuron specific enolase. Continuous transformation of myxoid tissue into cartilage together with corresponding reactivity for neuroectodermal marker proteins of myxoid cells and peripherally located chondrocytes suggest close relationship between myxoid cells and chondrocytes. The same criteria indicate relationship between myxoid cells and adipocytes. Coarse connective tissue, myxoid tissue, fibrous cartilage, and fat cells are functionally combined to absorb mechanical shock in the horse digital cushions.

Adipose Tissue↗
PubMed2006

Analysis and visualization of multiply oriented lattice structures by a two-dimensional continuous wavelet transform.

The phase-field-crystal model [K. R. Elder and M. Grant, Phys. Rev. E 70, 051605 (2004)] produces multigrain structures on atomistic length scale but on diffusive time scales. Since individual atoms are resolved but are treated identically it is difficult to distinguish the exact position of grain boundaries and defects within grains. In order to analyze and visualize the whole grains a two-dimensional wavelet transform has been developed, which is capable of extracting grain boundaries and the lattice orientation of a grain relative to a laboratory frame of reference. This transformation makes it possible not only to easily visualize the multigrain structure, but also to perform exact measurements on low- and high-angle boundaries, grain size distributions and boundary-angle distributions, which can then be compared to experimental data. The presented wavelet transform can also be applied to results of other atomistic simulations, e.g., molecular dynamics or granular materials.

Journal Article↗
PubMed2001

Tissue characterization using the continuous wavelet transform. Part II: Application on breast RF data.

In the first part of this work [16], a wavelet-based decomposition algorithm of the RF echo into its coherent and diffuse components was introduced. In this paper, the proposed algorithm is used to estimate structural parameters of the breast tissue such as the number and energy of coherent scatterers, the energy of the diffuse scatterers, and the correlation between them. Based on these individual parameters, breast tissue characterization is performed. The database used consists of 155 breast scans from 42 patients. The results are presented in terms of empirical receiver operating characteristics (ROC) curves. The results of this study are discussed in relation to the tissue microstructure. Individual estimated parameters are able to differentiate reliably between normal and fibroadenoma or fibrocystic or cancerous tissue (area under the ROC Az > 0.93). Also, the differentiation between malignant and benign (normal, fibrocystic, and fibroadenoma) tissue was possible (Az > 0.89).

Algorithms↗
PubMed2005

Spike detection using the continuous wavelet transform.

This paper combines wavelet transforms with basic detection theory to develop a new unsupervised method for robustly detecting and localizing spikes in noisy neural recordings. The method does not require the construction of templates, or the supervised setting of thresholds. We present extensive Monte Carlo simulations, based on actual extracellular recordings, to show that this technique surpasses other commonly used methods in a wide variety of recording conditions. We further demonstrate that falsely detected spikes corresponding to our method resemble actual spikes more than the false positives of other techniques such as amplitude thresholding. Moreover, the simplicity of the method allows for nearly real-time execution.

Action Potentials↗