Drug combination: pharmaceutical technologies applied to the manufacturing of combined dosage forms for oral administration

Lo scopo di questa ricerca di dottorato è stato lo studio di una forma di dosaggio flessibile e personalizzabile, indirizzata alle necessità individuali di ogni paziente, per il trattamento dell’iperplasia prostatica benigna. La terapia proposta prevede l’utilizzo di due farmaci, un alfa bloccante (farmaco A) e un inibitore delle 5- fosfodiesterasi (farmaco B) e, somministrati in una singola forma di dosaggio contenenti differenti dosi e combinazioni dei due farmaci. Lo sviluppo di un sistema di rilascio per la somministrazione orale di farmaco A e farmaco B è stato realizzato grazie alla tecnologia Dome Matrix. La tecnologia si basa sull’assemblaggio di moduli utilizzati come elementi di controllo del rilascio. L’assemblaggio dei moduli può essere ottenuto attraverso diverse configurazioni. Sono stati quindi realizzati sistemi assemblati in grado di galleggiare sul contenuto gastrico; la prolungata permanenza della forma farmaceutica nello stomaco favorisce la solubilizzazione dei due principi attivi che quindi potrebbero raggiungere il sito di assorbimento nel primo tratto intestinale già in dispersione molecolare, condizione ideale per essere assorbiti. La prima parte della ricerca è stata focalizzata sulla realizzazione di un sistema assemblato a rilascio modificato di farmaco A. Moduli contenenti diversi dosaggi di farmaco sono stati assemblati in varie configurazioni e dosi differenti per ottenere una forma di dosaggio flessibile, adattabile alle esigenze terapeutiche del paziente. La seconda parte del lavoro di tesi ha riguardato la realizzazione di un sistema assemblato, contenente entrambi i farmaci in associazione. L’ultima parte della ricerca è stata svolta presso la “University of Texas at Austin” sotto la supervisione del Professor Nicholas Peppas. Il lavoro svolto è stato focalizzato sullo studio delle caratteristiche di rigonfiamento dei singoli moduli di farmaco e dei loro sistemi assemblati; il comportamento di tali sistemi è stato investigato anche grazie all’utilizzo della tecnica di tomografia computerizzata a raggi X.

A representation of representation applied to a discussion of variable binding

States or state sequences in neural network models are made to represent concepts from applications. This paper motivates, introduces and discusses a formalism for denoting such representations; a representation for representations. The formalism is illustrated by using it to discuss the representation of variable binding and inference abstractly, and then to present four specific representations. One of these is an apparently novel hybrid of phasic and tensor-product representations which retains the desirable properties of each.

Description and critical appraisal of principal components analysis (PCA) methodology applied to pulsed-field gel electrophoresis profiles of methicillin-resistant Staphylococcus aureus isolates

Principal components analysis (PCA) has been described for over 50 years; however, it is rarely applied to the analysis of epidemiological data. In this study PCA was critically appraised in its ability to reveal relationships between pulsed-field gel electrophoresis (PFGE) profiles of methicillin- resistant Staphylococcus aureus (MRSA) in comparison to the more commonly employed cluster analysis and representation by dendrograms. The PFGE type following SmaI chromosomal digest was determined for 44 multidrug-resistant hospital-acquired methicillin-resistant S. aureus (MR-HA-MRSA) isolates, two multidrug-resistant community-acquired MRSA (MR-CA-MRSA), 50 hospital-acquired MRSA (HA-MRSA) isolates (from the University Hospital Birmingham, NHS Trust, UK) and 34 community-acquired MRSA (CA-MRSA) isolates (from general practitioners in Birmingham, UK). Strain relatedness was determined using Dice band-matching with UPGMA clustering and PCA. The results indicated that PCA revealed relationships between MRSA strains, which were more strongly correlated with known epidemiology, most likely because, unlike cluster analysis, PCA does not have the constraint of generating a hierarchic classification. In addition, PCA provides the opportunity for further analysis to identify key polymorphic bands within complex genotypic profiles, which is not always possible with dendrograms. Here we provide a detailed description of a PCA method for the analysis of PFGE profiles to complement further the epidemiological study of infectious disease. © 2005 Elsevier B.V. All rights reserved.

Negative data in DEA:a directional distance approach applied to bank branches

This paper is drawn from the use of data envelopment analysis (DEA) in helping a Portuguese bank to manage the performance of its branches. The bank wanted to set targets for the branches on such variables as growth in number of clients, growth in funds deposited and so on. Such variables can take positive and negative values but apart from some exceptions, traditional DEA models have hitherto been restricted to non-negative data. We report on the development of a model to handle unrestricted data in a DEA framework and illustrate the use of this model on data from the bank concerned.

Managing people and performance:An evidence based framework applied to health service organizations

People and their performance are key to an organization's effectiveness. This review describes an evidence-based framework of the links between some key organizational influences and staff performance, health and well-being. This preliminary framework integrates management and psychological approaches, with the aim of assisting future explanation, prediction and organizational change. Health care is taken as the focus of this review, as there are concerns internationally about health care effectiveness. The framework considers empirical evidence for links between the following organizational levels: 1. Context (organizational culture and inter-group relations; resources, including staffing; physical environment) 2. People management (HRM practices and strategies; job design, workload and teamwork; employee involvement and control over work; leadership and support) 3. Psychological consequences for employees (health and stress; satisfaction and commitment; knowledge, skills and motivation) 4. Employee behaviour (absenteeism and turnover; task and contextual performance; errors and near misses) 5. Organizational performance; patient care. This review contributes to an evidence base for policies and practices of people management and performance management. Its usefulness will depend on future empirical research, using appropriate research designs, sufficient study power and measures that are reliable and valid.

Functional source separation applied to induced visual gamma activity

Objective of this work was to explore the performance of a recently introduced source extraction method, FSS (Functional Source Separation), in recovering induced oscillatory change responses from extra-cephalic magnetoencephalographic (MEG) signals. Unlike algorithms used to solve the inverse problem, FSS does not make any assumption about the underlying biophysical source model; instead, it makes use of task-related features (functional constraints) to estimate source/s of interest. FSS was compared with blind source separation (BSS) approaches such as Principal and Independent Component Analysis, PCA and ICA, which are not subject to any explicit forward solution or functional constraint, but require source uncorrelatedness (PCA), or independence (ICA). A visual MEG experiment with signals recorded from six subjects viewing a set of static horizontal black/white square-wave grating patterns at different spatial frequencies was analyzed. The beamforming technique Synthetic Aperture Magnetometry (SAM) was applied to localize task-related sources; obtained spatial filters were used to automatically select BSS and FSS components in the spatial area of interest. Source spectral properties were investigated by using Morlet-wavelet time-frequency representations and significant task-induced changes were evaluated by means of a resampling technique; the resulting spectral behaviours in the gamma frequency band of interest (20-70 Hz), as well as the spatial frequency-dependent gamma reactivity, were quantified and compared among methods. Among the tested approaches, only FSS was able to estimate the expected sustained gamma activity enhancement in primary visual cortex, throughout the whole duration of the stimulus presentation for all subjects, and to obtain sources comparable to invasively recorded data.

Pulse compression applied to the detection of F.S.K. and P.S.K. signals

The matched filter detector is well known as the optimum detector for use in communication, as well as in radar systems for signals corrupted by Additive White Gaussian Noise (A.W.G.N.). Non-coherent F.S.K. and differentially coherent P.S.K. (D.P.S.K.) detection schemes, which employ a new approach in realizing the matched filter processor, are investigated. The new approach utilizes pulse compression techniques, well known in radar systems, to facilitate the implementation of the matched filter in the form of the Pulse Compressor Matched Filter (P.C.M.F.). Both detection schemes feature a mixer- P.C.M.F. Compound as their predetector processor. The Compound is utilized to convert F.S.K. modulation into pulse position modulation, and P.S.K. modulation into pulse polarity modulation. The mechanisms of both detection schemes are studied through examining the properties of the Autocorrelation function (A.C.F.) at the output of the P.C.M.F.. The effects produced by time delay, and carrier interference on the output A.C.F. are determined. Work related to the F.S.K. detection scheme is mostly confined to verifying its validity, whereas the D.P.S.K. detection scheme has not been reported before. Consequently, an experimental system was constructed, which utilized combined hardware and software, and operated under the supervision of a microprocessor system. The experimental system was used to develop error-rate models for both detection schemes under investigation. Performances of both F. S. K. and D.P. S. K. detection schemes were established in the presence of A. W. G. N. , practical imperfections, time delay, and carrier interference. The results highlight the candidacy of both detection schemes for use in the field of digital data communication and, in particular, the D.P.S.K. detection scheme, which performed very close to optimum in a background of A.W.G.N.

Vibrational methods applied to NDT testing and fluid density measurement

A system for the NDI' testing of the integrity of conposite materials and of adhesive bonds has been developed to meet industrial requirements. The vibration techniques used were found to be applicable to the development of fluid measuring transducers. The vibrational spectra of thin rectangular bars were used for the NDT work. A machined cut in a bar had a significant effect on the spectrum but a genuine crack gave an unambiguous response at high amplitudes. This was the generation of fretting crack noise at frequencies far above that of the drive. A specially designed vibrational decrement meter which, in effect, measures mechanical energy loss enabled a numerical classification of material adhesion to be obtained. This was used to study bars which had been flame or plasma sprayed with a variety of materials. It has become a useful tool in optimising coating methods. A direct industrial application was to classify piston rings of high performance I.C. engines. Each consists of a cast iron ring with a channel into which molybdenum, a good bearing surface, is sprayed. The NDT classification agreed quite well with the destructive test normally used. The techniques and equipment used for the NOT work were applied to the development of the tuning fork transducers investigated by Hassan into commercial density and viscosity devices. Using narrowly spaced, large area tines a thin lamina of fluid is trapped between them. It stores a large fraction of the vibrational energy which, acting as an inertia load reduces the frequency. Magnetostrictive and piezoelectric effects together or in combination enable the fork to be operated through a flange. This allows it to be used in pipeline or 'dipstick' applications. Using a different tine geometry the viscosity loading can be predoninant. This as well as the signal decrement of the density transducer makes a practical viscometer.

Numerical Comparison of the Drag Models of Granular Flows Applied to the Fast Pyrolysis of Biomass

The paper presents a comparison between the different drag models for granular flows developed in the literature and the effect of each one of them on the fast pyrolysis of wood. The process takes place on an 100 g/h lab scale bubbling fluidized bed reactor located at Aston University. FLUENT 6.3 is used as the modeling framework of the fluidized bed hydrodynamics, while the fast pyrolysis of the discrete wood particles is incorporated as an external user defined function (UDF) hooked to FLUENT’s main code structure. Three different drag models for granular flows are compared, namely the Gidaspow, Syamlal O’Brien, and Wen-Yu, already incorporated in FLUENT’s main code, and their impact on particle trajectory, heat transfer, degradation rate, product yields, and char residence time is quantified. The Eulerian approach is used to model the bubbling behavior of the sand, which is treated as a continuum. Biomass reaction kinetics is modeled according to the literature using a two-stage, semiglobal model that takes into account secondary reactions.