Purification of plasmid DNA for use in human gene therapy

Two key issues defined the focus of this research in manufacturing plasmid DNA for use In human gene therapy. First, the processing of E.coli bacterial cells to effect the separation of therapeutic plasmid DNA from cellular debris and adventitious material. Second, the affinity purification of the plasmid DNA in a Simple one-stage process. The need arises when considering the concerns that have been recently voiced by the FDA concerning the scalability and reproducibility of the current manufacturing processes in meeting the quality criteria of purity, potency, efficacy, and safety for a recombinant drug substance for use in humans. To develop a preliminary purification procedure, an EFD cross-flow micro-filtration module was assessed for its ability to effect the 20-fold concentration, 6-time diafiltration, and final clarification of the plasmid DNA from the subsequent cell lysate that is derived from a 1 liter E.coli bacterial cell culture. Historically, the employment of cross-flow filtration modules within procedures for harvesting cells from bacterial cultures have failed to reach the required standards dictated by existing continuous centrifuge technologies, frequently resulting in the rapid blinding of the membrane with bacterial cells that substantially reduces the permeate flux. By challenging the EFD module, containing six helical wound tubular membranes promoting centrifugal instabilities known as Dean vortices, with distilled water between the Dean number's of 187Dn and 818Dn,and the transmembrane pressures (TMP) of 0 to 5 psi. The data demonstrated that the fluid dynamics significantly influenced the permeation rate, displaying a maximum at 227Dn (312 Imh) and minimum at 818Dn (130 Imh) for a transmembrane pressure of 1 psi. Numerical studies indicated that the initial increase and subsequent decrease resulted from a competition between the centrifugal and viscous forces that create the Dean vortices. At Dean numbers between 187Dn and 227Dn , the forces combine constructively to increase the apparent strength and influence of the Dean vortices. However, as the Dean number in increases above 227 On the centrifugal force dominates the viscous forces, compressing the Dean vortices into the membrane walls and reducing their influence on the radial transmembrane pressure i.e. the permeate flux reduced. When investigating the action of the Dean vortices in controlling tile fouling rate of E.coli bacterial cells, it was demonstrated that the optimum cross-flow rate at which to effect the concentration of a bacterial cell culture was 579Dn and 3 psi TMP, processing in excess of 400 Imh for 20 minutes (i.e., concentrating a 1L culture to 50 ml in 10 minutes at an average of 450 Imh). The data demonstrated that there was a conflict between the Dean number at which the shear rate could control the cell fouling, and the Dean number at which tile optimum flux enhancement was found. Hence, the internal geometry of the EFD module was shown to sub-optimal for this application. At 579Dn and 3 psi TMP, the 6-fold diafiltration was shown to occupy 3.6 minutes of process time, processing at an average flux of 400 Imh. Again, at 579Dn and 3 psi TMP the clarification of the plasmid from tile resulting freeze-thaw cell lysate was achieved at 120 Iml1, passing 83% (2,5 mg) of the plasmid DNA (6,3 ng μ-1 10.8 mg of genomic DNA (∼23,00 Obp, 36 ng μ-1 ), and 7.2 mg of cellular proteins (5-100 kDa, 21.4 ngμ-1 ) into the post-EFD process stream. Hence the EFD module was shown to be effective, achieving the desired objectives in approximately 25 minutes. On the basis of its ability to intercalate into low molecular weight dsDNA present in dilute cell lysates, and be electrophoresed through agarose, the fluorophore PicoGreen was selected for the development of a suitable dsDNA assay. It was assesseel for its accuracy, and reliability, In determining the concentration and identity of DNA present in samples that were eleclrophoresed through agarose gels. The signal emitted by intercalated PicoGreen was shown to be constant and linear, and that the mobility of the PicaGreen-DNA complex was not affected by the intercalation. Concerning the secondary purification procedure, various anion-exchange membranes were assessed for their ability to capture plasmid DNA from the post-EFD process stream. For a commercially available Sartorius Sartobind Q15 membrane, the reduction in the equilibriumbinding capacity for  ctDNA in buffer of increasing ionic demonstrated that DNA was being.adsorbed by electrostatic  interactions only. However, the problems associated with fluid distribution across the membrane demonstrated that the membrane housing was the predominant cause of the .erratic breakthrough curves. Consequently, this would need to be rectified before such a membrane could be integrated into the current system, or indeed be scaled beyond laboratory scale. However, when challenged with the process material, the data showed that considerable quantities of protein (1150 μg) were adsorbed preferentially to the plasmid DNA (44 μg). This was also shown for derived Pall Gelman UltraBind US450 membranes that had been functionalised by varying molecular weight poly-L~lysine and polyethyleneimine ligands. Hence the anion-exchange membranes were shown to be ineffective in capturing plasmid DNA from the process stream. Finally, work was performed to integrate a sequence-specific DNA·binding protein into a single-stage DNA chromatography, isolating plasmid DNA from E.coli cells whilst minimising the contamination from genomic DNA and cellular protein. Preliminary work demonstrated that the fusion protein was capable of isolating pUC19 DNA into which the recognition sequence for the fusion-protein had been inserted (pTS DNA) when in the presence of the conditioned process material. Althougth the pTS recognition sequence differs from native pUC19 sequences by only 2 bp, the fusion protein was shown to act as a highly selective affinity ligand for pTS DNA alone. Subsequently, the scale of the process was scaled 25-fold and positioned directly following the EFD system. In conclusion, the integration of the EFD micro-filtration system and zinc-finger affinity purification technique resulted in the capture of approximately 1 mg of plasmid DNA was purified from 1L of E.coli  culture in a simple two stage process, resulting in the complete removal of genomic DNA and 96.7% of cellular protein in less than 1 hour of process time.

Octane requirement increase arising from the use of lead free fuel

Lead in petrol has been identified as a health hazard and attempts are being made to create a lead-free atmosphere. Through an intensive study a review is made of the various options available to the automobile and petroleum industry. The economic and atmospheric penalties coupled with automobile fuel consumption trends are calculated and presented in both graphical and tabulated form. Experimental measurements of carbon monoxide and hydrocarbon emissions are also presented for certain selected fuels. Reduction in CO and HC's with the employment of a three-way catalyst is also discussed. All tests were carried out on a Fiat 127A engine at wide open throttle and standard timing setting. A Froude dynamometer was used to vary engine speed. With the introduction of lead-free petrol, interest in combustion chamber deposits in spark ignition engines has ben renewed. These deposits cause octane requirement increase or rise in engine knock and decreased volumetric efficiency. The detrimental effect of the deposits has been attributed to the physical volume of the deposit and to changes in heat transfer. This study attempts to assess why leaded deposits, though often greater in mass and volume, yield relatively lower ORI when compared to lead-free deposits under identical operating conditions. This has been carried out by identifying the differences in the physical nature of the deposit and then through measurement of the thermal conductivity and permeability of the deposits. The measured thermal conductivity results are later used in a mathematical model to determine heat transfer rates and temperature variation across the engine wall and deposit. For the model, the walls of the combustion cylinder and top are assumed to be free of engine deposit, the major deposit being on the piston head. Seven different heat transfer equations are formulated describing heat flow at each part of the four stroke cycle, and the variation of cylinder wall area exposed to gas mixture is accounted for. The heat transfer equations are solved using numerical methods and temperature variations across the wall identified. Though the calculations have been carried out for one particular moment in the cycle, similar calculations are possible for every degree of the crank angle, and thus further information regarding location of maximum temperatures at every degree of the crank angle may also be determined. In conclusion, thermal conductivity values of leaded and lead-free deposits have been found. The fundamental concepts of a mathematical model with great potential have been formulated and it is hoped that with future work it may be used in a simulation for different engine construction materials and motor fuels, leading to better design of future prototype engines.

Synthesis and evaluation of novel ligands for quantum dot stabilisation and polymerisation studies

This thesis describes the design and synthesis of a variety of functionalised phosphine oxides and sulfides, based on the structure of trioctylphosphine oxide, synthesised for the purpose of surface modification of quantum dots. The ability of the ligands to modify the surface chemistry via displacement of the original hexadecylamine capping layer of quantum dots was evaluated. Finally the surface modified quantum dots were investigated for enhancement in their inherent properties and improved compatibility with the various applications for which they were initially designed. Upon the commencement of research involving quantum dots it became apparent that more information on their behaviour and interaction with the environment was required. The limits of the inherent stability of hexadecylamine capped quantum dots were investigated by exposure to a number of different environments. The effect upon the stability of the quantum dots was monitored by changes in the photoluminescence ability of their cores. Subtle differences between different batches of quantum dots were observed and the necessity to account for these in future applications noted. Lastly the displacement of the original hexadecylamine coating with the "designer" functionalised ligands was evaluated to produce a set of conditions that would result in the best possible surface modification. A general procedure was elucidated however it was discovered that each displacement still required slight adjustment by consideration of the other factors such as the difference in ligand structure and the individuality of the various batches of quantum dots. This thesis also describes a procedure for the addition of a protective layer to the surface of quantum dots by cross-linking the functionalised ligands bound to the surface via an acyclic diene metathesis polymerisation. A detailed description of the problems encountered in the analysis of these materials combined with the use of novel techniques such as diffusion ordered spectroscopy is provided as a means to overcome the limitations encountered. Finally a demonstration of the superior stability, upon exposure to a range of aggressive environments of these protected materials compared with those before cross-linking provided physical proof of the cross-linking process and the advantages of the cross-linking modification. Finally this thesis includes the presentation of initial work into the production of luminescent nanocrystal encoded resin beads for the specific use in solid phase combinatorial chemistry. Demonstration of the successful covalent incorporation of quantum dots into the polymeric matrices of non-functionalised and functionalised resin beads is described. Finally by preliminary work to address and overcome the possible limitations that may be encountered in the production and general employment of these materials in combinatorial techniques is given.

Control of antibiotic prescribing in UK NHS hosptials. Available in 2 volumes.

This thesis is an evaluation of practices to control antibiotic prescribing in UK NHS hospitals. Within the past ten years there has been increasing international concern about escalating antibiotic resistance, and the UK has issued several policy documents for pmdent antibiotic prescribing. Chief Pharmacists in 253 UK NHS hospitals were surveyed about the availability and nature of documents to control antibiotic prescribing (formularies, policies and guidelines), and the role of pharmacists and medical microbiologists in monitoring prescribers' compliance with the recommendations of such documents. Although 235 hospitals had at least one document, only 60% had both an antibiotic formulary and guidelines, and only about one-half planned an annual revision of document(s). Pharmacists were reported as mostly checking antibiotic prescribing on every ward whilst medical microbiologists mostly visited selected units only. Response to a similar questionnaire was obtained from the Chief Medical Microbiologists in 131 UK NHS hospitals. Comparisons of the questionnaires indicated areas of apparent disagreement about the roles of pharmacists and medical microbiologists. Eighty three paired-responses received from pharmacists and medical microbiologists in the same hospital revealed poor agreement and awareness about controls. A total of 205 institutional prescribing guidelines were analysed for recommendations for the empirical antibiotic prescribing of Community-Acquired Pneumonia (CAP). Variation was observed in recommendations and agreement with national guidance from the British Thoracic Society (BTS). A questionnaire was subsequently sent to 235 Chief Pharmacists to investigate their awareness of this new guidance from the BTS, and subsequent revision of institutional guidelines. Documents had been revised in only about one-half of hospitals where pharmacists were aware of the new guidance. An audit of empirical antibiotic prescribing practices for CAP was performed at one hospital. Although problems were experienced with retrieval of medical records, diagnostic criteria were poorly recorded, and only 57% of prescribing for non-severe CAP was compliant with institutional guidelines. A survey of clinicians at the same hospital identified that almost one-half used the institutional guidelines and most found them useful. However, areas for improvement concernmg awareness of the guidelines and ease of access were identified. It is important that hospitals are equipped to react to changes in the hospital environment including frequent movement of junior doctors between institutions, the employment of specialist "infectious diseases pharmacists" and the increasing benefits offered by information technology. Recommendations for policy have been suggested.

Development and application of magnetoencephalographic methods in the investigation of the human visual system

This thesis is an exploration of the organisation and functioning of the human visual system using the non-invasive functional imaging modality magnetoencephalography (MEG). Chapters one and two provide an introduction to the ‘human visual system and magnetoencephalographic methodologies. These chapters subsequently describe the methods by which MEG can be used to measure neuronal activity from the visual cortex. Chapter three describes the development and implementation of novel analytical tools; including beamforming based analyses, spectrographic movies and an optimisation of group imaging methods. Chapter four focuses on the use of established and contemporary analytical tools in the investigation of visual function. This is initiated with an investigation of visually evoked and induced responses; covering visual evoked potentials (VEPs) and event related synchronisation/desynchronisation (ERS/ERD). Chapter five describes the employment of novel methods in the investigation of cortical contrast response and demonstrates distinct contrast response functions in striate and extra-striate regions of visual cortex. Chapter six use synthetic aperture magnetometry (SAM) to investigate the phenomena of visual cortical gamma oscillations in response to various visual stimuli; concluding that pattern is central to its generation and that it increases in amplitude linearly as a function of stimulus contrast, consistent with results from invasive electrode studies in the macaque monkey. Chapter seven describes the use of driven visual stimuli and tuned SAM methods in a pilot study of retinotopic mapping using MEG; finding that activity in the primary visual cortex can be distinguished in four quadrants and two eccentricities of the visual field. Chapter eight is a novel implementation of the SAM beamforming method in the investigation of a subject with migraine visual aura; the method reveals desynchronisation of the alpha and gamma frequency bands in occipital and temporal regions contralateral to observed visual abnormalities. The final chapter is a summary of main conclusions and suggested further work.

The effect of major roads upon the local economy:a study of industrial location and its effects

The economic effects of road building (beyond those accounted for in cost-benefit analysis) are not well understood. This thesis examines the issues surrounding those effects and attempts to clarify the relationship between road building and industrial location and to identify the effect on employment of that location. The literature reviewed leads to some doubt as to the efficacy of roads as an economic tool. A scries of interviews with representatives of business and property professionals in three areas adjacent to motorways is carried out. These covered the firms' location or relocation decisions, their production costs, transport needs and employment. The conclusions drawn echo the above statements based on reviewed literature: 1. There was a general lack of knowledge of transport within a firm despite subjects' very good understanding of the rest of the firms' operations. 2. The importance of major roads to the business location decision and its perceived importance to the operations of the firms was low. Property professionals sec roads as an effective marketing tool. 3. Firms have a tendency to shed labour upon relocation although this does not necessarily constitute a net loss of employment but a redistribution. Recommendations are made for further research.

Development of science and technology policy for Kuwait

The status of Science and Technology in KUWAIT has been analysed in order to assess the extent of the application of Science and Technology needed for the Country's development. The design and implementation of a Science and Technology Policy has been examined to identify the appropriate technology necessary to improve KUWAIT's socio-economic-industrial structures. Following a general and critical review of the role of Science and Technology in the developing countries, the author has reviewed the past and contemporary employment of Science and Technology for development.of various sectors and the existence, if any, of any form (explicit, implicit, or both) of a Science and Technology Policy in KUWAIT. The thesis is structured to evaluate almost all of the sectors in KUWAIT which utilise Science and/or Technology, the effectiveness of such practices, their policymaking process, the channels by which policies were transformed into sources of influence through Governmental action and the impact that various policy instruments at the disposal of the the Government had on the development of S & T capabilities. The author has studied the implications of the absence of a Science and Technology Policy in Kuwait by examining some specific case studies, eg, the absence of a Technology Assessment Process and the negative impacts resulting from this; the ad-hoc allocation of the research and development budget instead of its being based on a percentage of GNP; the limitations imposed on the development of indigenous contracting companies and consultancy and engineering design offices; the impacts of the absence of Technology Transfer Centre, and so forth. As a consequence of the implications of the above studies, together with the negative results from the absence of an explicit Science and Technology Policy, eg, research and development activities do not relate to the national development plans, the author suggests that a Science and Technology Policy-Making Body should be established to formulate, develop, monitor and correlate the Science and Technology Activities in KUWAIT.

The formulation of artificial reference standards for use within the ELISPOT assay

Whether to assess the functionality of equipment or as a determinate for the accuracy of assays, reference standards are essential for the purposes of standardisation and validation. The ELISPOT assay, developed over thirty years ago, has emerged as a leading immunological assay in the development of novel vaccines for the assessment of efficacy. However, with its widespread use, there is a growing demand for a greater level of standardisation across different laboratories. One of the major difficulties in achieving this goal has been the lack of definitive reference standards. This is partly due to the ex vivo nature of the assay, which relies on cells being placed directly into the wells. Thus, the aim of this thesis was to produce an artificial reference standard using liposomes, for use within the assay. Liposomes are spherical bilayer vesicles with an enclosed aqueous compartment and therefore are models for biological membranes. Initial work examined pre-design considerations in order to produce an optimal formulation that would closely mimic the action of the cells ordinarily placed on the assay. Recognition of the structural differences between liposomes and cells led to the formulation of liposomes with increased density. This was achieved by using a synthesised cholesterol analogue. By incorporating this cholesterol analogue in liposomes, increased sedimentation rates were observed within the first few hours. The optimal liposome formulation from these studies was composed of 2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), cholesterol (Chol) and brominated cholesterol (Brchol) at a 16:4:12 µMol ratio, based on a significantly higher (p<0.01) sedimentation (as determined by a percentage transmission of 59 ± 5.9 % compared to the control formulation at 29 ± 12 % after four hours). By considering a range of liposome formulations ‘proof of principle’ for using liposomes as ELISPOT reference standards was shown; recombinant IFN? cytokine was successfully entrapped within vesicles of different lipid compositions, which were able to promote spot formation within the ELISPOT assay. Using optimised liposome formulations composed of phosphatidylcholine with or without cholesterol (16 µMol total lipid) further development was undertaken to produce an optimised, scalable protocol for the production of liposomes as reference standards. A linear increase in spot number by the manipulation of cytokine concentration and/or lipid concentrations was not possible, potentially due to the saturation that occurred within the base of wells. Investigations into storage of the formulations demonstrated the feasibility of freezing and lyophilisation with disaccharide cryoprotectants, but also highlighted the need for further protocol optimisation to achieve a robust reference standard upon storage. Finally, the transfer of small-scale production to a medium lab-scale batch (40 mL) demonstrated this was feasible within the laboratory using the optimised protocol.

Externalizing, internalizing and fostering commitment:the case of born-global firms in emerging economies

This paper examines the HR practices of mature born-global firms from 29 emerging economies. Through an examination of large scale survey data the paper questions the extent to which firm size impacts the employment of temporary workers, the employment of skilled workers and the extent of employee training. Findings suggest that as firm size increases the use of temporary workers decreases, the number of skilled workers increases and the number of employees receiving training also increases. The paper highlights how born-global firms are able to shift away from externalized, market-based approaches towards more internalized, commitment-based approaches in order to survive, adapt and grow.

Early Detection of Emergent Events Based on an Extremal Process Approach

2000 Mathematics Subject Classification: Primary 60G70, 62F03.

A vállalati likviditáskezelés szerepe eszközfedezettel rendelkező hitelszerződésekben. Az alkun alapuló megközelítés eredményei (The role of corporate liquidity management under secured debt financing Results of the bargaining approach)

A szerző azt a kérdést vizsgálja, hogy a vállalat működése során a likvid eszközök mekkora arányát tartsa fenn. A kérdést a finanszírozás szemszögéből veti fel, mivel a hitelezés okozta korlátok jelentősen befolyásolják a likvid eszköz tartalékolásának motivációit. A cikk a vállalkozói-hitelezői információs kapcsolat háromféle esetében mutatja be az eszközfedezettel rendelkező hitelek adósságszolgálatát meghatározó tényezőket. Elsőként a teljes információs viszony melletti stratégiákkal meghatározott adósságszolgálatot vizsgálja, majd a második típusú információs kapcsolatban a nem megfigyelhető vállalkozói erőfeszítéseket feltételezve adja meg az adósságszolgálat fizetésének ex ante és ex post egyensúlyát. Harmadikként, a nem igazolható vállalati adatok feltevése mellett teljes és részleges eszközfedezetre is meghatározza az optimális vállalkozói likviditási politikát, és tárgyalja az itt fennálló ellentéteket. Megmutatja, hogy részleges eszközfedezet mellett 1. újratárgyalható a hitelszerződés, és a stratégiai adósságszolgálatot nem lehet elkerülni, 2. a likviditásoptimalizálásnak nincs ex post Pareto-egyensúlyi megoldása, ugyanis a hitelszerződésben részt vevő felek alkuereje határozza meg a vállalat likviditásának szintjét. / === / This paper investigates what the liquid asset ratio for firms should be. Financing constraints significantly influence motivations for liquidity hoarding. The article shows the determinants of secured debt services for three different information cases of a lender-borrower relationship. First, it examines the strategic debt service under full information, and then, assuming non-observable entrepreneurial efforts, it gives the ex ante and ex post equilibria of the strategic debt service. The third case supposes non-verifiable firm information; this provides the optimal corporate liquidity policy and explains the contrary propositions. It shows that under not fully secured collateral, 1. the debt contract is renegotiable; the lender cannot avoid the strategic debt service, 2. there is no ex post optimal Pareto efficient solution to liquidity policy, because the corporate liquidity ratio is determined by the bargaining power of the partners in the debt contract.

A lean termelési rendszer munkásokra gyakorolt hatása (Effects of lean production on quality of working life from workers’ point of view)

A lean termelési rendszer munkásokra gyakorolt hatásaival foglalkozó irodalomban nincsen egyetértés annak megítélésében, hogy a hatásokban a negatív vagy pozitív hatások dominálnak-e. A szerző tanulmánya ehhez a vitához a pszichológiai, egészségügyi, munkahelyi jellemzőkre és a dolgozói elégedettségre vonatkozó eredmények áttekintésével kapcsolódik. A munkások elégedettségének vizsgálata arra utal, hogy a lean termelési rendszer egyszerre növeli és csökkenti is az elégedettséget, így az összességében nem változik más termelési rendszerekhez képest. A lean termelés kritikusai azt hangsúlyozzák, hogy a többi tényező negatívan hat a munkásokra. Megállapításaik megalapozottsága a nagyon kevés empirikus munka miatt megkérdőjelezhető. Ugyanakkor a tevékenységmenedzsment kutatói érdemben nem tudják cáfolni a stressz, a sérülések és betegségek kockázatának növekedését és a munka intenzívebbé válását. A negatív hatások és a várt pozitív hatások hiányának kiemelése felveti, hogy a munkavállalók bevonásán alapuló lean termelési rendszer nehezen ültethető át a gyakorlatba, illetve hogy a lean termelés intenzifikáción alapuló modellje is elterjedt. _____________ This literature review contributes to the debate related to the effects of lean production on workers. The study reviews different dimensions of the debate and focuses on issues like worker’s satisfaction, psychological effects, health and safety aspects, and workplace characteristics. Findings of researches reviewed in this paper cannot confirm that from workers’ point of view lean production is better than other production initiatives. Lean production enhances and decreases worker’s satisfaction at the same time, altogether, the satisfaction of workers does not change significantly compared to other systems. The negative impact of the other factors (psychological etc.) on workers is usually emphasized in the critique of lean production. Although, the limited number of (empirical) studies doubts these critical voices. However, Operations Management can not reject negative effects like increasing level of stress, increased risks of health and safety problems or intensification of work. The emphasis of the negative effects and the lack of positive effects can refer to the difficult employment of lean involvement system, or simply reflect that the model of lean intensification system is widely spread.

A desztináció menedzsment szerepe a desztinációs versenyképességben – Hazai és dán tapasztalatok tükrében = The role of destination management in the destinations’ competitiveness – Hungarian and Danish experiences

A desztináció menedzsment valamennyi desztinációs versenyképesség modell középponti eleme, és „csodaszerként” jelenik meg, különösen azokban az országokban, amelyek a desztináció menedzsment eszközrendszerét a közelmúltban vezették be, annak érdekében, hogy a desztinációk lépést tudjanak tartani a versenytársaikkal, mint ahogyan ez hazánkban is történt. Jelen tanulmány alapját a témában írt PhD Értekezésem (Sziva, I. (2010)) adja, amelynek fókuszában a desztinációs versenyképesség értelmezése, az ex ante oldali tényezők feltárása állt. A téziskutatás során feltárt tényezők, és a Bírálóim konstruktív fejlesztési javaslatai a téma továbbkutatására ösztönöztek. Mindezért tartottam elengedhetetlennek, hogy a tézisemben összefoglalt hazai és osztrák kutatások legfontosabb eredményeit további nemzetközi színtéren, ezúttal Dániában vizsgáljam, jelen esetben a fókuszt a desztináció menedzsment tényezőire, és annak kiemelt kontextusaira helyezve. Jelen tanulmány legfontosabb célja az, hogy egyrészt összefoglalást adjon a desztináció menedzsment szerepéről a desztinációs versenyképesség elméleti megközelítéseit tekintve. Továbbá, hogy a hazai tapasztalatok összevetésre kerüljenek a szakértői interjúk során megismert dán tapasztalatokkal és további kutatási irányok kerüljenek meghatározásra. Ezúton szeretném megköszönni dániai kutatásom interjú-alanyainak részvételét és a Budapesti Corvinus Egyetem TÁMOP 4.2.1.B-09/1/KMR-2010-0005 projekt keretében nyújtott támogatását! _________ Destination management is the central element of the model concerning destinations’ competitiveness, and appears as „wonder medicine”, particularly in those countries, where the tools of destination management was introduced in the near past, as it happened in Hungary. The baseline of this study is given by my PhD Dissertation (Sziva, I. (2010)), which was focusing on interpretation and the ex ante factors of destinations’ competitiveness. The factors identified during my thesis research, and the constructive recommendations of my Reviewer gave the motivation for further analysis. That is why was it important to make further researchers based on the results identified in the Hungarian and Austrian cases of my thesis research, and add further international, this time Danish context to the research, by focusing on destination management among the factors of competitiveness. The aim of the article is to give a summary about the theoretical approach of destination management and compare the Hungarian experiences with that of the results of the Danish research based on experts’ interviews. Hereby I would like to thank my interviewees their participation, and the support of Corvinus University Budapest in the framework of TÁMOP 4.2.1.B-09/1/KMR-2010-0005 project.

A minimálbér költségvetési hatásai = The budgetary effects of the minimum wage

A minimálbér-emelés a munkapiacon közvetlenül hat a keresletre és a kínálatra. Közvetett hatásai azonban túlmutatnak a munkapiacon, ezért azokat egy makromodell keretei között elemezzük. A makromodellben háromféle munkafajta és tíz ágazat van; az egyes ágazatok az árképzésükben és az adó- és járulékelkerülésük szerkezetében különböznek. A minimálbér-emelés munkapiaci feszültséget generál: csökkenti a foglalkoztatást a szakképzetlenek körében. Mivel az árszint az átlagbérnél gyorsabban nő, és az aggregált foglalkoztatás is csökken, így csökken a reálfogyasztás. A vállalatok profitja és beruházása csökken, ugyanakkor a vállalati profit csökkenése már csekély mértékű adóelkerülés-növeléssel is kiegyensúlyozható. A minimálbér-emelés hatására nőnek ugyan az adóbevételek, viszont a kiadások nagyobb mértékben nőnek, így általában romlik az egyenleg. Aki tehát a minimálbér emelését követeli, annak a felelős döntés során számolnia kell ezekkel a következményekkel. _____ Raising the minimum wage on the labour market has direct effects on supply and demand. But its indirect effects extend beyond the labour market. They are analysed here with a macro model that distinguishes three types of work and ten industries, whose firms differ in their price structures and the degrees to which tax and social-insurance payments are avoided. Raising the minimum wage generates tension on the labour market and reduces employment of the unskilled. Since the price level rises faster than average pay and aggregate employment falls, so does real consumption. The firms’ profits and investment decline, but the former can be offset even by a small increase in tax avoidance. Although the rise in the minimum wage boosts tax revenues, budgetary expenditures rise more and the balance deteriorates. Advocates of a higher minimum wage need to consider these consequences if they are to reach a responsible decision.

Adult education directors' perceptions of performance indicators for adult education programs in the state of Florida

Current demands for accountability in education emphasize outcome-based program evaluation and tie program funding to individual student performance. As has been the case for elementary and secondary programs, demands for accountability have increased pressure on adult educators to show evidence of the benefits of their programs in order to justify their financial support. In Florida, recent legislation fundamentally changes the delivery of adult education in the state by establishing a performance-based funding system that is based on outcomes related to the retention, completion, and employment of program participants.^ A performance-based funding system requires an evaluation process that stresses outcome indicators over indicators that focus on program context or process. Although the state has adopted indicators of program quality to evaluate its adult education programs, these indicators focus mostly on program processes rather than student outcomes. In addition, the indicators are not specifically tied to workforce development outcomes, a priority to federal and local funding agents.^ Improving the accountability of adult education programs and defining the role of these programs in Florida's Workforce Development System has become a priority to policy makers across the state. Another priority has been to involve adult education practitioners in every step of this process.^ This study was conducted in order to determine what performance indicators, as judged by the directors and supervisors of adult education programs in the state of Florida, are important and feasible in measuring the quality and effectiveness of these programs. The results of the study indicated that, both statewide and by region, the respondents consistently gave the highest ratings on both importance and feasibility to the indicators of Program Context, which reflect the needs, composition, and structure of the programs, and to the indicators of Educational Gain, which reflect learner progress in the attainment of basic skills and competencies. In turn, the respondents gave the lowest ratings on both importance and feasibility to the indicators in the areas of Return on State's Investment, Efficiency, Retention, and Workforce Training. In general, the indicators that received high ratings for importance also received high ratings for feasibility. ^