Actions of the Kunitz-type serine protease inhibitor Amblyomin-X on VEGF-A-induced angiogenesis

Amblyomin-X is a Kunitz-type serine protease inhibitor (Kunitz-type SPI) designed from the cDNA library of the Amblyomma cajennense tick, which displays in vivo anti-tumor activities. Here, the mechanisms of actions of Amblyomin-X in vascular endothelial growth factor A (VEGF-A)-induced angiogenesis were characterized. Topical application of Amblyomin-X (10 or 100 ng/10 mu l; each 48 h) inhibited VEGF-A-induced (10 ng/10 mu l; each 48 h) angiogenesis in the dorsal subcutaneous tissue in male Swiss mice. Moreover, similar effect was observed in the VEGF-A-induced angiogenesis in the chicken chorioallantoic membrane (CAM). Additional in vitro assays in t-End cells showed that Amblyomin-X treatment delayed the cell cycle, by maintaining them in G0/G1 phase, and inhibited cell proliferation and adhesion, tube formation and membrane expression of the adhesion molecule platelet-endothelial cell adhesion molecule-1 (PECAM-I), regardless of mRNA synthesis. Together, results herein reveal the role of Kunitz-type SPI on in vivo VEGF-A-induced angiogenesis, by exerting modulatory actions on endothelial cell proliferation and adhesion, especially on membrane expression of PECAM-1. These data provide further mechanisms of actions of Kunitz-type SPI, corroborating their relevance as scientific tools in the design of therapeutic molecules. (C) 2012 Elsevier Ltd. All rights reserved.

The Constitutional-Judicial Control of the Legislative and Executive Powers in Central and Eastern European Countries

This project looked at the nature, contents, methods, means and legal and political effects of the influence that constitutional courts exercise upon the legislative and executive powers in the newly established democracies of Central and Eastern Europe. The basic hypothesis was that these courts work to provide a limitation of political power within the framework of the principal constitutional values and that they force the legislature and executive to exercise their powers and duties in strict accordance with the constitution. Following a study of the documentary sources, including primarily the relevant constitutional and statutory provisions and decisions of constitutional courts, Mr. Cvetkovski prepared a questionnaire on various aspects of the topics researched and sent it to the respective constitutional courts. A series of direct interviews with court officials in six of the ten countries then served to clarify a large number of questions relating to differences in procedures etc. that arose from the questionnaires. As a final stage, the findings were compared with those described in recent publications on constitutional control in general and in Central and Eastern Europe in particular. The study began by considering the constitutional and political environment of the constitutional courts' activities in controlling legislative and executive powers, which in all countries studied are based on the principles of the rule of law and the separation of powers. All courts are separate bodies with special status in terms of constitutional law and are independent of other political and judicial institutions. The range of matters within their jurisdiction is set by the constitution of the country in question but in all cases can be exercised only with the framework of procedural rules. This gives considerable significance to the question of who sets these rules and different countries have dealt with it in different ways. In some there is a special constitutional law with the same legal force as the constitution itself (Croatia), the majority of countries allow for regulation by an ordinary law, Macedonia gives the court the autonomy to create and change its own rules of procedure, while in Hungary the parliament fixes the rules on procedure at the suggestion of the constitutional court. The question of the appointment of constitutional judges was also considered and of the mechanisms for ensuring their impartiality and immunity. In the area of the courts' scope for providing normative control, considerable differences were found between the different countries. In some cases the courts' jurisdiction is limited to the normative acts of the respective parliaments, and there is generally no provision for challenging unconstitutional omissions by legislation and the executive. There are, however, some situations in which they may indirectly evaluate the constitutionality of legislative omissions, as when the constitution contains provision for a time limit on enacting legislation, when the parliament has made an omission in drafting a law which violates the constitutional provisions, or when a law grants favours to certain groups while excluding others, thereby violating the equal protection clause of the constitution. The control of constitutionality of normative acts can be either preventive or repressive, depending on whether it is implemented before or after the promulgation of the law or other enactment being challenged. In most countries in the region the constitutional courts provide only repressive control, although in Hungary and Poland the courts are competent to perform both preventive and repressive norm control, while in Romania the court's jurisdiction is limited to preventive norm control. Most countries are wary of vesting constitutional courts with preventive norm control because of the danger of their becoming too involved in the day-to-day political debate, but Mr. Cvetkovski points out certain advantages of such control. If combined with a short time limit it can provide early clarification of a constitutional issue, secondly it avoids the problems arising if a law that has been in force for some years is declared to be unconstitutional, and thirdly it may help preserve the prestige of the legislation. Its disadvantages include the difficulty of ascertaining the actual and potential consequences of a norm without the empirical experience of the administration and enforcement of the law, the desirability of a certain distance from the day-to-day arguments surrounding the political process of legislation, the possible effects of changing social and economic conditions, and the danger of placing obstacles in the way of rapid reactions to acute situations. In the case of repressive norm control, this can be either abstract or concrete. The former is initiated by the supreme state organs in order to protect abstract constitutional order and the latter is initiated by ordinary courts, administrative authorities or by individuals. Constitutional courts cannot directly oblige the legislature and executive to pass a new law and this remains a matter of legislative and executive political responsibility. In the case of Poland, the parliament even has the power to dismiss a constitutional court decision by a special majority of votes, which means that the last word lies with the legislature. As the current constitutions of Central and Eastern European countries are newly adopted and differ significantly from the previous ones, the courts' interpretative functions should ensure a degree of unification in the application of the constitution. Some countries (Bulgaria, Hungary, Poland, Slovakia and Russia) provide for the constitutional courts' decisions to have a binding role on the constitutions. While their decisions inevitably have an influence on the actions of public bodies, they do not set criteria for political behaviour, which depends rather on the overall political culture and traditions of the society. All constitutions except that of Belarus, provide for the courts to have jurisdiction over conflicts arising from the distribution of responsibilities between different organs and levels in the country, as well for impeachment procedures against the head of state, and for determining the constitutionality of political parties (except in Belarus, Hungary, Russia and Slovakia). All the constitutions studied guarantee individual rights and freedoms and most courts have jurisdiction over complaints of violation of these rights by the constitution. All courts also have some jurisdiction over international agreements and treaties, either directly (Belarus, Bulgaria and Hungary) before the treaty is ratified, or indirectly (Croatia, Czech Republic, Macedonia, Romania, Russia and Yugoslavia). In each country the question of who may initiate proceedings of norm control is of central importance and is usually regulated by the constitution itself. There are three main possibilities: statutory organs, normal courts and private individuals and the limitations on each of these is discussed in the report. Most courts are limited in their rights to institute ex officio a full-scale review of a point of law, and such rights as they do have rarely been used. In most countries courts' decisions do not have any binding force but must be approved by parliament or impose on parliament the obligation to bring the relevant law into conformity within a certain period. As a result, the courts' position is generally weaker than in other countries in Europe, with parliament remaining the supreme body. In the case of preventive norm control a finding of unconstitutionality may act to suspend the law and or to refer it back to the legislature, where in countries such as Romania it may even be overturned by a two-thirds majority. In repressive norm control a finding of unconstitutionality generally serves to take the relevant law out of legal force from the day of publication of the decision or from another date fixed by the court. If the law is annulled retrospectively this may or may not bring decisions of criminal courts under review, depending on the provisions laid down in the relevant constitution. In cases relating to conflicts of competencies the courts' decisions tend to be declaratory and so have a binding effect inter partes. In the case of a review of an individual act, decisions generally become effective primarily inter partes but is the individual act has been based on an unconstitutional generally binding normative act of the legislature or executive, the findings has quasi-legal effect as it automatically initiates special proceedings in which the law or other regulation is to be annulled or abrogated with effect erga omnes. This wards off further application of the law and thus further violations of individual constitutional rights, but also discourages further constitutional complaints against the same law. Thus the success of one individual's complaint extends to everyone else whose rights have equally been or might have been violated by the respective law. As the body whose act is repealed is obliged to adopt another act and in doing so is bound by the legal position of the constitutional court on the violation of constitutionally guaranteed freedoms and rights of the complainant, in this situation the decision of the constitutional court has the force of a precedent.

Determination of external and internal mass transfer limitation in nitrifying microbial aggregates

In this article we present a study of the effects of external and internal mass transfer limitation of oxygen in a nitrifying system. The oxygen uptake rates (OUR) were measured on both a macro-scale with a respirometric reactor using off-gas analysis (Titrimetric and Off-Gas Analysis (TOGA) sensor) and on a micro-scale with microsensors. These two methods provide independent, accurate measurements of the reaction rates and concentration profiles around and in the granules. The TOGA sensor and micro-sensor measurements showed a significant external mass transfer effect at low dissolved oxygen (DO) concentrations in the bulk liquid while it was insignificant at higher DO concentrations. The oxygen distribution with anaerobic or anoxic conditions in the center clearly shows major mass transfer limitation in the aggregate interior. The large drop in DO concentration of 22 - 80% between the bulk liquid and aggregate surface demonstrates that the external mass transfer resistance is also highly important. The maximum OUR even for floccular biomass was only attained at much higher DO concentrations ( approximate to 8 mg/L) than typically used in such systems. For granules, the DO required for maximal activity was estimated to be > 20mg/L, clearly indicating the effects of the major external and internal mass transfer limitations on the overall biomass activity. Smaller aggregates had a larger volumetric OUR indicating that the granules may have a lower activity in the interior part of the aggregate. (C) 2004 Wiley Periodicals, Inc.

Impacts of high-nitrate freshwater inputs on macrotidal ecosystems. I. Seasonal evolution of nutrient limitation for the diatom-dominated phytoplankton of the Bay of Brest (France)

The chemical factors (inorganic nitrogen, phosphate, silicic acid) that potentially or actually control primary production were determined for the Bay of Brest, France, a macrotidal ecosystem submitted to high-nitrate-loaded freshwater inputs (winter nitrate freshwater concentrations >700 mu M, Si:N molar ratio as low as 0.2, i.e. among the lowest ever published). Intensive data collection and observations were carried out from February 1993 to March 1994 to determine the variations of physical [salinity, temperature, photosynthetically active radiation (PAR), freshwater discharges] and chemical (oxygen and nutrients) parameters and their impacts on the phytoplankton cycle (fluorescence, pigments, primary production). With insufficient PAR the winter stocks of nutrients were almost nonutilized and the nitrate excess was exported to the adjacent ocean, due to rapid tidal exchange. By early April, a diatom-dominated spring bloom developed (chlorophyll a maximum = 7.7 mu g l(-1); primary production maximum = 2.34 g C m(-2) d(-1)) under high initial nutrient concentrations. Silicic acid was rapidly exhausted over the whole water column; it is inferred to be the primary limiting factor responsible for the collapse of the spring bloom by mid-May. Successive phytoplankton developments characterized the period of secondary blooms during summer and fall (successive surface chlorophyll a maxima = 3.5, 1.6, 1.8 and 1.0 mu g l(-1); primary production = 1.24, 1.18 and 0.35 g C m(-2) d(-1)). Those secondary blooms developed under lower nutrient concentrations, mostly originating from nutrient recycling. Until August, Si and P most likely limited primary production, whereas the last stage of the productive period in September seemed to be N limited instead, this being a period of total nitrate depletion in almost the whole water column. Si limitation of spring blooms has become a common feature in coastal ecosystems that receive freshwater inputs with Si:N molar ratios <1. The peculiarity of Si Limitation in the Bay of Brest is its extension through the summer period.

Longitudinal Student Evaluations of a Postgraduate Unit Using Importance-Performance Analysis

The Australian tourism tertiary education sector operates in a competitive and dynamic environment, which necessitates a market orientation to be successful. Academic staff and management in the sector must regularly assess the perceptions of prospective and current students, and monitor the satisfaction levels of current students. This study is concerned with the setting and monitoring of satisfaction levels of current students, reporting the results of three longitudinal investigations of student satisfaction in a postgraduate unit. The study also addresses a limitation of a university’s generic teaching evaluation instrument. Importance-performance analysis (IPA) has been recommended as a simple but effective tool for overcoming the deficiencies of many student evaluation studies, which have generally measured only attribute importance or importance at the end of a semester. IPA was used to compare student expectations of the unit at the beginning of semester with their perceptions of performance ten weeks later. The first stage documented key benchmarks for which amendments to the unit based on student feedback could be evaluated during subsequent teaching periods.

Conceptions of school based youth health nursing : a phenomenographic study

The School Based Youth Health Nurse Program was established in 1999 by the Queensland Government to fund school nurse positions in Queensland state high schools. Schools were required to apply for a School Based Youth Health Nurse during a five-phase recruitment process, managed by the health districts, and rolled out over four years. The only mandatory selection criterion for the position of School Based Youth Health Nurse was registration as a General Nurse and most School Based Youth Health Nurses are allocated to two state high schools. Currently, there are approximately 115 Full Time Equivalent School Based Youth Health Nurse positions across all Queensland state high schools. The literature review revealed an abundance of information about school nursing. Most of the literature came from the United Kingdom and the United States, who have a different model of school nursing to school based youth health nursing. However, there is literature to suggest school nursing is gradually moving from a disease-focused approach to a social view of health. The noticeable number of articles about, for example, drug and alcohol, mental health, and contemporary sexual health issues, is evidence of this change. Additionally, there is a significant the volume of literature about partnerships and collaboration, much of which is about health education, team teaching and how school nurses and schools do health business together. The surfacing of this literature is a good indication that school nursing is aligning with the broader national health priority areas. More particularly, the literature exposed a small but relevant and current body of research, predominantly from Queensland, about school based youth health nursing. However, there remain significant gaps in the knowledge about school based youth health nursing. In particular, there is a deficit about how School Based Youth Heath Nurses understand the experience of school based youth health nursing. This research aimed to reveal the meaning of the experience of school based youth health nursing. The research question was How do School Based Youth Health Nurses’ understand the experience of school based youth health nursing? This enquiry was instigated because the researcher, who had a positive experience of school based youth health nursing, considered it important to validate other School Based Youth Health Nurses’ experiences. Consequently, a comprehensive use of qualitative research was considered the most appropriate manner to explore this research question. Within this qualitative paradigm, the research framework consists of the epistemology of social constructionism, the theoretical perspective of interpretivism and the approach of phenomenography. After ethical approval was gained, purposeful and snowball sampling was used to recruit a sample of 16 participants. In-depth interviews, which were voluntary, confidential and anonymous, were mostly conducted in public venues and lasted from 40-75 minutes. The researcher also kept a researchers journal as another form of data collection. Data analysis was guided by Dahlgren and Fallsbergs’ (1991, p. 152) seven phases of data analysis which includes familiarization, condensation, comparison, grouping, articulating, labelling and contrasting. The most important finding in this research is the outcome space, which represents the entirety of the experience of school based youth health nursing. The outcome space consists of two components: inside the school environment and outside the school environment. Metaphorically and considered as whole-in-themselves, these two components are not discreet but intertwined with each other. The outcome space consists of eight categories. Each category of description is comprised of several sub-categories of description but as a whole, is a conception of school based youth health nursing. The eight conceptions of school based youth health nursing are: 1. The conception of school based youth health nursing as out there all by yourself. 2. The conception of school based youth health nursing as no real backup. 3. The conception of school based youth health nursing as confronted by many barriers. 4. The conception of school based youth health nursing as hectic and full-on. 5. The conception of school based youth health nursing as working together. 6. The conception of school based youth health nursing as belonging to school. 7. The conception of school based youth health nursing as treated the same as others. 8. The conception of school based youth health nursing as the reason it’s all worthwhile. These eight conceptions of school based youth health nursing are logically related and form a staged hierarchical relationship because they are not equally dependent on each other. The conceptions of school based youth health nursing are grouped according to negative, negative and positive and positive conceptions of school based youth health nursing. The conceptions of school based youth health nursing build on each other, from the bottom upwards, to reach the authorized, or the most desired, conception of school based youth health nursing. This research adds to the knowledge about school nursing in general but especially about school based youth health nursing specifically. Furthermore, this research has operational and strategic implications, highlighted in the negative conceptions of school based youth health nursing, for the School Based Youth Health Nurse Program. The researcher suggests the School Based Youth Health Nurse Program, as a priority, address the operational issues The researcher recommends a range of actions to tackle issues and problems associated with accommodation and information, consultations and referral pathways, confidentiality, health promotion and education, professional development, line management and School Based Youth Health Nurse Program support and school management and community. Strategically, the researcher proposes a variety of actions to address strategic issues, such as the School Based Youth Health Nurse Program vision, model and policy and practice framework, recruitment and retention rates and evaluation. Additionally, the researcher believes the findings of this research have the capacity to spawn a myriad of future research projects. The researcher has identified the most important areas for future research as confidentiality, information, qualifications and health outcomes.

Outrage management in cases of sexual harassment as revealed in judicial decisions

Sexual harassment can be conceptualized as a series of interactions between harassers and targets that either inhibit or increase outrage by third parties. The outrage management model predicts the kinds of actions likely to be used by perpetrators to minimize outrage, predicts the consequences of failing to use these tactics—namely backfire, and recommends countertactics to increase outrage. Using this framework, our archival study examined outrage-management tactics reported as evidence in 23 judicial decisions of sexual harassment cases in Australia. The decisions contained precise, detailed information about the circumstances leading to the claim; the events which transpired in the courtroom, including direct quotations; and the judges' interpretations and findings. We found evidence that harassers minimize outrage by covering up the actions, devaluing the target, reinterpreting the events, using official channels to give an appearance of justice, and intimidating or bribing people involved. Targets can respond using countertactics of exposure, validation, reframing, mobilization of support, and resistance. Although there are limitations to using judicial decisions as a source of information, our study points to the value of studying tactics and the importance to harassers of minimizing outrage from their actions. The findings also highlight that, given the limitations of statutory and organizational protections in reducing the incidence and severity of sexual harassment in the community, individual responses may be effective as part of a multilevel response in reducing the incidence and impact of workplace sexual harassment as a gendered harm.

Contribution of cross-functional teams to the improvement in operational performance

Purpose: The purpose of this paper is to explore the role of cross-functional teams in the alignment between system effectiveness and operational effectiveness after the implementation of enterprise information systems (EIS). In addition, it aims to explore the contribution of cross-functional teams to improvement in operational performance. ---------- Design/methodology/approach: The research uses a combination of qualitative and quantitative methods, in a two-stage methodological approach, to investigate the influence of cross-functional teams on the alignment between system effectiveness and operational effectiveness and the impact of the stated alignment on the improvement in operational performance. ---------- Findings: Initial findings suggest that factors stemming from system effectiveness and the performance objectives stemming from operational effectiveness are important and significantly well correlated factors that promote the alignment between the effectiveness of technological implementation and the effectiveness of operations. In addition, confirmatory factor analysis has been used to find the structural relationships and provide explanations for the stated alignment and the contribution of cross-functional teams to the improvement in operational performance. ---------- Research limitations/implications: The principal limitation of this study is its small sample size. ---------- Practical implications: Cross-functional teams have been used by many organisations as a way of involving expertise from different functional areas in the implementation of innovative technologies. An appropriate use of the dimensions that emerged from this research, in the context of cross-functional teams, will assist organisations to properly utilise cross-functional teams with the aim of improving operational performance. ---------- Originality/value: The paper presents a new approach to measure the effectiveness of EIS implementation by adding new dimensions to measure it.

Constraints of nutrient availability on primary production in two alpine tundra communities

A nutrient amendment experiment was conducted for two growing seasons in two alpine tundra communities to test the hypotheses that: (1) primary production is limited by nutrient availability, and (2) physiological and developmental constraints act to limit the responses of plants from a nutrient-poor community more than plants from a more nutrient-rich community to increases in nutrient availability. Experimental treatments consisted of N, P, and N+P amendments applied to plots in two physiognomically similar communities, dry and wet meadows. Extractable N and P from soils in nonfertilized control plots indicated that the wet meadow had higher N and P availability. Photosynthetic, nutrient uptake, and growth responses of the dominants in the two communities showed little difference in the relative capacity of these plants to respond to the nutrient additions. Aboveground production responses of the communities to the treatments indicated N availability was limiting to production in the dry meadow community while N and P availability colimited production in the wet meadow community. There was a greater production response to the N and N+P amendments in the dry meadow relative to the wet meadow, despite equivalent functional responses of the dominant species of both communities. The greater production response in the dry meadow was in part related to changes in community structure, with an increase in the proportion of graminoid and forb biomass, and a decrease in the proportion of community biomass made up by the dominant sedge Kobresia myosuroides. Species richness increased significantly in response to the N+P treatment in the dry meadow. Graminoid biomass increased significantly in the wet meadow N and N+P plots, while forb biomass decreased significantly, suggesting a competitive interaction for light. Thus, the difference in community response to nutrient amendments was not the result of functional changes at the leaf level of the dominant species, but rather was related to changes in community structure in the dry meadow, and to a shift from a nutrient to a light limitation of production in the wet meadow.

Understanding the impact of strategic alignment on the operational performance of post implemented technological innovations

Purpose – The purpose of this paper is to examine the role of three strategies - organisational, business and information system – in post implementation of technological innovations. The findings reported in the paper are that improvements in operational performance can only be achieved by aligning technological innovation effectiveness with operational effectiveness. Design/methodology/approach – A combination of qualitative and quantitative methods was used to apply a two-stage methodological approach. Unstructured and semi structured interviews, based on the findings of the literature, were used to identify key factors used in the survey instrument design. Confirmatory factor analysis (CFA) was used to examine structural relationships between the set of observed variables and the set of continuous latent variables. Findings – Initial findings suggest that organisations looking for improvements in operational performance through adoption of technological innovations need to align with operational strategies of the firm. Impact of operational effectiveness and technological innovation effectiveness are related directly and significantly to improved operational performance. Perception of increase of operational effectiveness is positively and significantly correlated with improved operational performance. The findings suggest that technological innovation effectiveness is also positively correlated with improved operational performance. However, the study found that there is no direct influence of strategiesorganisational, business and information systems (IS) - on improvement of operational performance. Improved operational performance is the result of interactions between the implementation of strategies and related outcomes of both technological innovation and operational effectiveness. Practical implications – Some organisations are using technological innovations such as enterprise information systems to innovate through improvements in operational performance. However, they often focus strategically only on effectiveness of technological innovation or on operational effectiveness. Such a focus will be detrimental in the long-term of the enterprise. This research demonstrated that it is not possible to achieve maximum returns through technological innovations as dimensions of operational effectiveness need to be aligned with technological innovations to improve their operational performance. Originality/value – No single technological innovation implementation can deliver a sustained competitive advantage; rather, an advantage is obtained through the capacity of an organisation to exploit technological innovations’ functionality on a continuous basis. To achieve sustainable results, technology strategy must be aligned with organisational and operational strategies. This research proposes the key performance objectives and dimensions that organisations should focus to achieve a strategic alignment. Research limitations/implications – The principal limitation of this study is that the findings are based on investigation of small sample size. There is a need to explore the appropriateness of influence of scale prior to generalizing the results of this study.

Longitudinal evaluations of student satisfaction with a postgraduate unit using importance-performance analysis

The Australian tourism tertiary education sector operates in a competitive and dynamic environment, which necessitates a market orientation to be successful. Academic staff and management in the sector must regularly assess the perceptions of prospective and current students and monitor the satisfaction levels of current students. This study is concerned with the setting and monitoring of satisfaction levels of current students, reporting the results of three longitudinal investigations of student satisfaction in a postgraduate unit. The study also addresses a limitation of a university’s generic teaching evaluation instrument. Importance-Performance Analysis (IPA) has been recommended as a simple but effective tool for overcoming the deficiencies of many student evaluation studies, which have generally measured only attribute performance at the end of a semester. IPA was used to compare student expectations of the unit at the beginning of a semester with their perceptions of performance 10 weeks later. The first stage documented key benchmarks for which amendments to the unit based on student feedback could be evaluated during subsequent teaching periods.

Non-invasive assessment of tear film surface quality

The tear film plays an important role preserving the health of the ocular surface and maintaining the optimal refractive power of the cornea. Moreover dry eye syndrome is one of the most commonly reported eye health problems. This syndrome is caused by abnormalities in the properties of the tear film. Current clinical tools to assess the tear film properties have shown certain limitations. The traditional invasive methods for the assessment of tear film quality, which are used by most clinicians, have been criticized for the lack of reliability and/or repeatability. A range of non-invasive methods of tear assessment have been investigated, but also present limitations. Hence no “gold standard” test is currently available to assess the tear film integrity. Therefore, improving techniques for the assessment of the tear film quality is of clinical significance and the main motivation for the work described in this thesis. In this study the tear film surface quality (TFSQ) changes were investigated by means of high-speed videokeratoscopy (HSV). In this technique, a set of concentric rings formed in an illuminated cone or a bowl is projected on the anterior cornea and their reflection from the ocular surface imaged on a charge-coupled device (CCD). The reflection of the light is produced in the outer most layer of the cornea, the tear film. Hence, when the tear film is smooth the reflected image presents a well structure pattern. In contrast, when the tear film surface presents irregularities, the pattern also becomes irregular due to the light scatter and deviation of the reflected light. The videokeratoscope provides an estimate of the corneal topography associated with each Placido disk image. Topographical estimates, which have been used in the past to quantify tear film changes, may not always be suitable for the evaluation of all the dynamic phases of the tear film. However the Placido disk image itself, which contains the reflected pattern, may be more appropriate to assess the tear film dynamics. A set of novel routines have been purposely developed to quantify the changes of the reflected pattern and to extract a time series estimate of the TFSQ from the video recording. The routine extracts from each frame of the video recording a maximized area of analysis. In this area a metric of the TFSQ is calculated. Initially two metrics based on the Gabor filter and Gaussian gradient-based techniques, were used to quantify the consistency of the pattern’s local orientation as a metric of TFSQ. These metrics have helped to demonstrate the applicability of HSV to assess the tear film, and the influence of contact lens wear on TFSQ. The results suggest that the dynamic-area analysis method of HSV was able to distinguish and quantify the subtle, but systematic degradation of tear film surface quality in the inter-blink interval in contact lens wear. It was also able to clearly show a difference between bare eye and contact lens wearing conditions. Thus, the HSV method appears to be a useful technique for quantitatively investigating the effects of contact lens wear on the TFSQ. Subsequently a larger clinical study was conducted to perform a comparison between HSV and two other non-invasive techniques, lateral shearing interferometry (LSI) and dynamic wavefront sensing (DWS). Of these non-invasive techniques, the HSV appeared to be the most precise method for measuring TFSQ, by virtue of its lower coefficient of variation. While the LSI appears to be the most sensitive method for analyzing the tear build-up time (TBUT). The capability of each of the non-invasive methods to discriminate dry eye from normal subjects was also investigated. The receiver operating characteristic (ROC) curves were calculated to assess the ability of each method to predict dry eye syndrome. The LSI technique gave the best results under both natural blinking conditions and in suppressed blinking conditions, which was closely followed by HSV. The DWS did not perform as well as LSI or HSV. The main limitation of the HSV technique, which was identified during the former clinical study, was the lack of the sensitivity to quantify the build-up/formation phase of the tear film cycle. For that reason an extra metric based on image transformation and block processing was proposed. In this metric, the area of analysis was transformed from Cartesian to Polar coordinates, converting the concentric circles pattern into a quasi-straight lines image in which a block statistics value was extracted. This metric has shown better sensitivity under low pattern disturbance as well as has improved the performance of the ROC curves. Additionally a theoretical study, based on ray-tracing techniques and topographical models of the tear film, was proposed to fully comprehend the HSV measurement and the instrument’s potential limitations. Of special interested was the assessment of the instrument’s sensitivity under subtle topographic changes. The theoretical simulations have helped to provide some understanding on the tear film dynamics, for instance the model extracted for the build-up phase has helped to provide some insight into the dynamics during this initial phase. Finally some aspects of the mathematical modeling of TFSQ time series have been reported in this thesis. Over the years, different functions have been used to model the time series as well as to extract the key clinical parameters (i.e., timing). Unfortunately those techniques to model the tear film time series do not simultaneously consider the underlying physiological mechanism and the parameter extraction methods. A set of guidelines are proposed to meet both criteria. Special attention was given to a commonly used fit, the polynomial function, and considerations to select the appropriate model order to ensure the true derivative of the signal is accurately represented. The work described in this thesis has shown the potential of using high-speed videokeratoscopy to assess tear film surface quality. A set of novel image and signal processing techniques have been proposed to quantify different aspects of the tear film assessment, analysis and modeling. The dynamic-area HSV has shown good performance in a broad range of conditions (i.e., contact lens, normal and dry eye subjects). As a result, this technique could be a useful clinical tool to assess tear film surface quality in the future.

A forced titration study of the antioxidant and immunomodulatory effects of Ambrotose AO supplement

Background Oxidative stress plays a role in acute and chronic inflammatory disease and antioxidant supplementation has demonstrated beneficial effects in the treatment of these conditions. This study was designed to determine the optimal dose of an antioxidant supplement in healthy volunteers to inform a Phase 3 clinical trial. Methods The study was designed as a combined Phase 1 and 2 open label, forced titration dose response study in healthy volunteers (n = 21) to determine both acute safety and efficacy. Participants received a dietary supplement in a forced titration over five weeks commencing with a no treatment baseline through 1, 2, 4 and 8 capsules. The primary outcome measurement was ex vivo changes in serum oxygen radical absorbance capacity (ORAC). The secondary outcome measures were undertaken as an exploratory investigation of immune function. Results A significant increase in antioxidant activity (serum ORAC) was observed between baseline (no capsules) and the highest dose of 8 capsules per day (p = 0.040) representing a change of 36.6%. A quadratic function for dose levels was fitted in order to estimate a dose response curve for estimating the optimal dose. The quadratic component of the curve was significant (p = 0.047), with predicted serum ORAC scores increasing from the zero dose to a maximum at a predicted dose of 4.7 capsules per day and decreasing for higher doses. Among the secondary outcome measures, a significant dose effect was observed on phagocytosis of granulocytes, and a significant increase was also observed on Cox 2 expression. Conclusion This study suggests that Ambrotose AO® capsules appear to be safe and most effective at a dosage of 4 capsules/day. It is important that this study is not over interpreted; it aimed to find an optimal dose to assess the dietary supplement using a more rigorous clinical trial design. The study achieved this aim and demonstrated that the dietary supplement has the potential to increase antioxidant activity. The most significant limitation of this study was that it was open label Phase 1/Phase 2 trial and is subject to potential bias that is reduced with the use of randomization and blinding. To confirm the benefits of this dietary supplement these effects now need to be demonstrated in a Phase 3 randomised controlled trial (RCT).

Boundary weaving : the social structure and processes of organizational boundaries

Boundaries are an important field of study because they mediate almost every aspect of organizational life. They are becoming increasingly more important as organizations change more frequently and yet, despite the endemic use of the boundary metaphor in common organizational parlance, they are poorly understood. Organizational boundaries are under-theorized and researchers in related fields often simply assume their existence, without defining them. The literature on organizational boundaries is fragmented with no unifying theoretical basis. As a result, when it is recognized that an organizational boundary is "dysfunctional". there is little recourse to models on which to base remediating action. This research sets out to develop just such a theoretical model and is guided by the general question: "What is the nature of organizational boundaries?" It is argued that organizational boundaries can be conceptualised through elements of both social structure and of social process. Elements of structure include objects, coupling, properties and identity. Social processes include objectification, identification, interaction and emergence. All of these elements are integrated by a core category, or basic social process, called boundary weaving. An organizational boundary is a complex system of objects and emergent properties that are woven together by people as they interact together, objectifying the world around them, identifying with these objects and creating couplings of varying strength and polarity as well as their own fragmented identity. Organizational boundaries are characterised by the multiplicity of interconnections, a particular domain of objects, varying levels of embodiment and patterns of interaction. The theory developed in this research emerged from an exploratory, qualitative research design employing grounded theory methodology. The field data was collected from the training headquarters of the New Zealand Army using semi-structured interviews and follow up observations. The unit of analysis is an organizational boundary. Only one research context was used because of the richness and multiplicity of organizational boundaries that were present. The model arose, grounded in the data collected, through a process of theoretical memoing and constant comparative analysis. Academic literature was used as a source of data to aid theory development and the saturation of some central categories. The final theory is classified as middle range, being substantive rather than formal, and is generalizable across medium to large organizations in low-context societies. The main limitation of the research arose from the breadth of the research with multiple lines of inquiry spanning several academic disciplines, with some relevant areas such as the role of identity and complexity being addressed at a necessarily high level. The organizational boundary theory developed by this research replaces the typology approaches, typical of previous theory on organizational boundaries and reconceptualises the nature of groups in organizations as well as the role of "boundary spanners". It also has implications for any theory that relies on the concept of boundaries, such as general systems theory. The main contribution of this research is the development of a holistic model of organizational boundaries including an explanation of the multiplicity of boundaries . no organization has a single definable boundary. A significant aspect of this contribution is the integration of aspects of complexity theory and identity theory to explain the emergence of higher-order properties of organizational boundaries and of organizational identity. The core category of "boundary weaving". is a powerful new metaphor that significantly reconceptualises the way organizational boundaries may be understood in organizations. It invokes secondary metaphors such as the weaving of an organization's "boundary fabric". and provides managers with other metaphorical perspectives, such as the management of boundary friction, boundary tension, boundary permeability and boundary stability. Opportunities for future research reside in formalising and testing the theory as well as developing analytical tools that would enable managers in organizations to apply the theory in practice.

Unlocking black box models of leadership effectiveness: Exploring alternative research and policy metaphors

There is an intimate interconnectivity between policy guidelines defining reform and the delineation of what research methods would be subsequently applied to determine reform success. Research is guided as much by the metaphors describing it as by the ensuing empirical definition of actions of results obtained from it. In a call for different reform policy metaphors Lumby and English (2010) note, “The primary responsibility for the parlous state of education... lies with the policy makers that have racked our schools with reductive and dehumanizing processes, following the metaphors of market efficiency, and leadership models based on accounting and the characteristics of machine bureaucracy” (p. 127)