Pharmaceutical process optimisation of bulk lyophilisates:implications of powder handling

Lyophilisation or freeze drying is the preferred dehydrating method for pharmaceuticals liable to thermal degradation. Most biologics are unstable in aqueous solution and may use freeze drying to prolong their shelf life. Lyophilisation is however expensive and has seen lots of work aimed at reducing cost. This thesis is motivated by the potential cost savings foreseen with the adoption of a cost efficient bulk drying approach for large and small molecules. Initial studies identified ideal formulations that adapted well to bulk drying and further powder handling requirements downstream in production. Low cost techniques were used to disrupt large dried cakes into powder while the effects of carrier agent concentration were investigated for powder flowability using standard pharmacopoeia methods. This revealed superiority of crystalline mannitol over amorphous sucrose matrices and established that the cohesive and very poor flow nature of freeze dried powders were potential barriers to success. Studies from powder characterisation showed increased powder densification was mainly responsible for significant improvements in flow behaviour and an initial bulking agent concentration of 10-15 %w/v was recommended. Further optimisation studies evaluated the effects of freezing rates and thermal treatment on powder flow behaviour. Slow cooling (0.2 °C/min) with a -25°C annealing hold (2hrs) provided adequate mechanical strength and densification at 0.5-1 M mannitol concentrations. Stable bulk powders require powder transfer into either final vials or intermediate storage closures. The targeted dosing of powder formulations using volumetric and gravimetric powder dispensing systems where evaluated using Immunoglobulin G (IgG), Lactate Dehydrogenase (LDH) and Beta Galactosidase models. Final protein content uniformity in dosed vials was assessed using activity and protein recovery assays to draw conclusions from deviations and pharmacopeia acceptance values. A correlation between very poor flowability (p<0.05), solute concentration, dosing time and accuracy was revealed. LDH and IgG lyophilised in 0.5 M and 1 M mannitol passed Pharmacopeia acceptance values criteria with 0.1-4 while formulations with micro collapse showed the best dose accuracy (0.32-0.4% deviation). Bulk mannitol content above 0.5 M provided no additional benefits to dosing accuracy or content uniformity of dosed units. This study identified considerations which included the type of protein, annealing, cake disruption process, physical form of the phases present, humidity control and recommended gravimetric transfer as optimal for dispensing powder. Dosing lyophilised powders from bulk was demonstrated as practical, time efficient, economical and met regulatory requirements in cases. Finally the use of a new non-destructive technique, X-ray microcomputer tomography (MCT), was explored for cake and particle characterisation. Studies demonstrated good correlation with traditional gas porosimetry (R2 = 0.93) and morphology studies using microscopy. Flow characterisation from sample sizes of less than 1 mL was demonstrated using three dimensional X-ray quantitative image analyses. A platinum-mannitol dispersion model used revealed a relationship between freezing rate, ice nucleation sites and variations in homogeneity within the top to bottom segments of a formulation.

Ensuring QoE in contemporary mobile networks for video content distribution

A framework that aims to best utilize the mobile network resources for video applications is presented in this paper. The main contribution of the work proposed is the QoE-driven optimization method that can maintain a desired trade-off between fairness and efficiency in allocating resources in terms of data rates to video streaming users in LTE networks. This method is concerned with the control of the user satisfaction level from the service continuity's point of view and applies appropriate QoE metrics (Pause Intensity and variations) to determine the scheduling strategies in combination with the mechanisms used for adaptive video streaming such as 3GP/MPEG-DASH. The superiority of the proposed algorithms are demonstrated, showing how the resources of a mobile network can be optimally utilized by using quantifiable QoE measurements. This approach can also find the best match between demand and supply in the process of network resource distribution.

A semantic paradigm for intelligent data access

An implementation of Sem-ODB—a database management system based on the Semantic Binary Model is presented. A metaschema of Sem-ODB database as well as the top-level architecture of the database engine is defined. A new benchmarking technique is proposed which allows databases built on different database models to compete fairly. This technique is applied to show that Sem-ODB has excellent efficiency comparing to a relational database on a certain class of database applications. A new semantic benchmark is designed which allows evaluation of the performance of the features characteristic of semantic database applications. An application used in the benchmark represents a class of problems requiring databases with sparse data, complex inheritances and many-to-many relations. Such databases can be naturally accommodated by semantic model. A fixed predefined implementation is not enforced allowing the database designer to choose the most efficient structures available in the DBMS tested. The results of the benchmark are analyzed. ^ A new high-level querying model for semantic databases is defined. It is proven adequate to serve as an efficient native semantic database interface, and has several advantages over the existing interfaces. It is optimizable and parallelizable, supports the definition of semantic userviews and the interoperability of semantic databases with other data sources such as World Wide Web, relational, and object-oriented databases. The query is structured as a semantic database schema graph with interlinking conditionals. The query result is a mini-database, accessible in the same way as the original database. The paradigm supports and utilizes the rich semantics and inherent ergonomics of semantic databases. ^ The analysis and high-level design of a system that exploits the superiority of the Semantic Database Model to other data models in expressive power and ease of use to allow uniform access to heterogeneous data sources such as semantic databases, relational databases, web sites, ASCII files, and others via a common query interface is presented. The Sem-ODB engine is used to control all the data sources combined under a unified semantic schema. A particular application of the system to provide an ODBC interface to the WWW as a data source is discussed. ^

Boundary maintenance in Qatar: Interpretation of domination, segregation and subordination

This study explores the interaction of expatriates in Qatar and their perception of their subordination. The study design included participant observation in an all female University and University housing as well as interviews with Qatari government agencies and ministries, expatriate embassies and expatriates. Semi-structured interviews were conducted across seven expatriate groups: domestic workers, unskilled laborers, semiskilled, professionals, housewives, second-generation expatriates with host country other than Qatar, second-generation expatriates with host country Qatar, and Gulf Cooperation Council citizens. Forty-two subjects completed the interview schedule while 87 interviews were incomplete. ^ Physical control of expatriates occurs through the Gulf practice of sponsorship (The Kafeel System), and local cultural and Islamic related controls intertwined with the Arab Code of honor. Interviews and observations revealed rankings of Arabs and foreigners which emphasize Qatari superiority such as tribal identity, moral ranking of female groups by dress, legal protection and power, sexual consideration and desexualization and salaries and job opportunities based on nationality and ethnicity. Individuals who desire to transcend boundaries into the Qatari realm through citizenship or marriage view Qataris as possessing the “image of the unlimited good” and have acquired Qatari social and cultural capital. Members from all expatriate groups engaged in various forms of resistance to labor and gender domination which ranged from forms of “exit,” expressing a hidden transcript in the privacy of their own group, disguised resistance in public, and occasionally, direct confrontation with the Qatari. Although the legal arena created the appearance that worker's needs were being addressed, laborers engaged in forms of “exit” to escape their oppression. Omani students in the hostel disguised their resistance by spreading gossip, nick-naming homosexual Qatari students at the University, acting out a skit depicting their exclusion from Qatari privilege, spreading rumors of impending freedom, and singing songs of despair in the courtyard. Other sites of resistance were expatriate embassies, the road, the newspaper and technology. This study emphasizes that blaming oppression of the expatriate worker on globalization is a simplistic view of oppression in the Gulf, and ignores complex issues within Qatari society and other Gulf States. Sponsorship, servitude, and gender segregation intersect in Qatar to create a system of segregation and domination of expatriates. ^

Essays on international macroeconomics and conflict analysis

This dissertation addressed two broad problems in international macroeconomics and conflict analysis. The first problem in the first chapter looked at the behavior of exchange rate and its interaction with industry-level tradable goods prices for three countries, USA, UK and Japan. This question has important monetary policy implications. Here, I computed to what extent changes in exchange rate affected prices of consumer, producer, and export goods. I also studied the timing of these changes in these prices. My results, based on thirty-four industrial prices for USA, UK and Japan, supported the view that changes in exchange rates significantly affect prices of industrial and consumer goods. It also provided an insight to the underlying economic process that led to changes in relative prices. ^ In the second chapter, I explored the predictability of future inflation by incorporating shocks to exchange rates and clearly specified the transmission mechanisms that link exchange rates to industry-level consumer and producer prices. Employing a variety of linear and state-of-the-art nonlinear models, I also predicted growth rates of future prices. Comparing levels of inflation obtained from the above approaches showed superiority of the structural model incorporating the exchange rate pass-through effect. ^ The second broad issue addressed in the third chapter of the dissertation investigated the economic motives for conflict, manifested by rebellion and civil war for seventeen Latin American countries. Based on the analytical framework of Garfinkel, Skaperdas and Syropoulos (2004), I employed ordinal regressions and Markov switching for a panel of seventeen countries to identify trade and openness factors responsible for conflict occurrence and intensity. The results suggested that increased trade openness reduced high intensity domestic conflicts but overdependence on agricultural exports, along with a lack of income earning opportunities lead to more conflicts. Thereafter, using the Cox Proportional Hazard model I studied “conflict duration” and found that over-reliance on agricultural exports explained a major part of the length of conflicts in addition to various socio-political factors. ^

An exergy based engineering and economic analysis of sustainable building

To achieve the goal of sustainable development, the building energy system was evaluated from both the first and second law of thermodynamics point of view. The relationship between exergy destruction and sustainable development were discussed at first, followed by the description of the resource abundance model, the life cycle analysis model and the economic investment effectiveness model. By combining the forgoing models, a new sustainable index was proposed. Several green building case studies in U.S. and China were presented. The influences of building function, geographic location, climate pattern, the regional energy structure, and the technology improvement potential of renewable energy in the future were discussed. The building’s envelope, HVAC system, on-site renewable energy system life cycle analysis from energy, exergy, environmental and economic perspective were compared. It was found that climate pattern had a dramatic influence on the life cycle investment effectiveness of the building envelope. The building HVAC system energy performance was much better than its exergy performance. To further increase the exergy efficiency, renewable energy rather than fossil fuel should be used as the primary energy. A building life cycle cost and exergy consumption regression model was set up. The optimal building insulation level could be affected by either cost minimization or exergy consumption minimization approach. The exergy approach would cause better insulation than cost approach. The influence of energy price on the system selection strategy was discussed. Two photovoltaics (PV) systems—stand alone and grid tied system were compared by the life cycle assessment method. The superiority of the latter one was quite obvious. The analysis also showed that during its life span PV technology was less attractive economically because the electricity price in U.S. and China did not fully reflect the environmental burden associated with it. However if future energy price surges and PV system cost reductions were considered, the technology could be very promising for sustainable buildings in the future.

A research platform for artificial neural networks with applications in pediatric epilepsy

This dissertation established a state-of-the-art programming tool for designing and training artificial neural networks (ANNs) and showed its applicability to brain research. The developed tool, called NeuralStudio, allows users without programming skills to conduct studies based on ANNs in a powerful and very user friendly interface. A series of unique features has been implemented in NeuralStudio, such as ROC analysis, cross-validation, network averaging, topology optimization, and optimization of the activation function’s slopes. It also included a Support Vector Machines module for comparison purposes. Once the tool was fully developed, it was applied to two studies in brain research. In the first study, the goal was to create and train an ANN to detect epileptic seizures from subdural EEG. This analysis involved extracting features from the spectral power in the gamma frequencies. In the second application, a unique method was devised to link EEG recordings to epileptic and nonepileptic subjects. The contribution of this method consisted of developing a descriptor matrix that can be used to represent any EEG file regarding its duration and the number of electrodes. The first study showed that the inter-electrode mean of the spectral power in the gamma frequencies and its duration above a specific threshold performs better than the other frequencies in seizure detection, exhibiting an accuracy of 95.90%, a sensitivity of 92.59%, and a specificity of 96.84%. The second study yielded that Hjorth’s parameter activity is sufficient to accurately relate EEG to epileptic and non-epileptic subjects. After testing, accuracy, sensitivity and specificity of the classifier were all above 0.9667. Statistical tests measured the superiority of activity at over 99.99 % certainty. It was demonstrated that (1) the spectral power in the gamma frequencies is highly effective in locating seizures from EEG and (2) activity can be used to link EEG recordings to epileptic and non-epileptic subjects. These two studies required high computational load and could be addressed thanks to NeuralStudio. From a medical perspective, both methods proved the merits of NeuralStudio in brain research applications. For its outstanding features, NeuralStudio has been recently awarded a patent (US patent No. 7502763).

Representation of people of color in the nineteenth century slavery novel in Cuba and Brazil

This dissertation explores the similarities and differences which characterize the depiction of people of color in certain representative nineteenth century Cuban and Brazilian slavery novels as a function of the authorial approach of each territory's literary tradition toward the issues of slavery, racial prejudice, and people of color. The selected texts, derived from the peak periods in slavery literature of each territory, include Francisco , by Anselmo Snárez y Romero; Sab, by Gertrudis Gómez de Avellaneda; Cecilia Valdés , by Cirilo Villaverde; A escrava Isaura, by Bernardo Guimarães; O mulato, by Aluísio Azevedo; and Bom-Crioulo, by Adolfo Caminha. While the present study explores the enslavement, abuse, and discrimination of people of color as a consequence of a deep-seated discourse of power, privilege and racial superiority, it focuses more extensively on the representation of people of color, particularly in their capacity to constructively appropriate the cultural values of the white dominant group and recognize their identity as ambiguous. ^ Said's theories of Orientalist discourse and geography and formation as well as Dube's perspective on subaltern-oriented studies provide a theoretical framework for exploring the response of slavery writers whose common exposure to slavery but dissimilar socio-political contexts generate some startling findings. Crafted within a period of political repression, fear of black revolt, factional in-fighting as well as strong socioeconomic ties to the slaveholding class, the Cuban texts generally fashioned an approach to slavery as one marked by moderation, reform, and cultural counter discourse and consequently depict people of color with a more passive but culturally authentic outlook. On the other hand, the Brazilian response to the issue of slavery, steeped in an ideological amalgam of liberalism, positivism, republicanism, and abolitionism, is characterized by overt opposition to slavery and a representation of people of color that is less concerned with cross-cultural input but reclaims their humanity as highly educable and socially mobile persons in search of greater freedoms. Ultimately, there is a shared message of higher significance couched in the worthwhile mission of raising slaves to the level of men. ^

An Historical Look at Gender in the ESL Classroom

The role that gender plays with respect to language learning in the classroom is ripe for investigation. Some educators and researchers maintain that females possess superior language skills. This author argues that ideas regarding female language superiority are suspect and may encourage discriminatory pedagogy for women as well as men.

An examination of the within -product category versus across -product category effects of partially comparative pricing

Partially comparative pricing involves a featured store providing price comparisons in reference to a competitor for some products (comparatively priced products) while omitting such comparisons and providing only its price for other products (non-comparatively priced products). Barone, Manning and Miniard (2004) found that while partially comparative pricing enhanced consumers' price perceptions of comparatively priced products at the featured retailer, it had the opposite effect for non-comparatively priced products (i.e., an inferiority effect). To the contrary, it is argued that a price comparison for one brand in a product category may enhance consumers' price perceptions of the remaining, non-comparatively priced brands within the same product category (i.e., a superiority effect). This research seeks to (a) examine the robustness of partially comparative pricing's effect in an across-product category context compared to a within-product category context and (b) extend the understanding of partially comparative pricing's within-product category effect on non-comparatively priced brands by examining potential moderators of this effect: brand diversity, brand typicality, and the relative expensiveness of the brand receiving the price comparison. The findings of four studies provide evidence to support the presence of a superiority effect in a within-product category context and suggests that the adverse effect of partially comparative pricing in an across-product category context may not be as robust as previously thought. Although the superiority effect was unaffected by brand diversity (i.e., whether the brands emanated from different manufacturers or from a single manufacturer), it was found to be moderated by the typicality of the brand receiving the price comparison as well as the comparison brand's relative expensiveness. Research participants formed more favorable relative price beliefs about the non-comparatively priced brand when the comparatively priced brand was perceived as a more typical member of the product category. Similarly, participants formed more favorable beliefs about the non-comparatively priced brand when the comparison price was assigned to the most expensive brand in the product category rather than the least expensive brand.

Individual child cognitive behavioral treatment versus child-parent cognitive behavioral treatments for anxiety disorders in children and adolescents: Comparative outcomes

Anxiety disorders; such as separation anxiety disorder, generalized anxiety disorder, social phobia and specific phobia, are widespread in children and adolescents. Cognitive behavioral therapy (CBT) has been shown to be effective in reducing excessive fears and anxieties in children and adolescents. Research has produced equivocal findings that involving parents in treatment of child anxiety enhances effects over individual CBT (ICBT). The present dissertation study examined whether parental involvement can enhance individual treatment effect if the parent conditions are streamlined by targeting specific parental variables. The first parent condition, Parent Reinforcement Skills Training (RFST), involved increasing mothers' use of positive reinforcement and decreasing use of negative reinforcement. The second parent condition, Parent Relationship Skill Training (RLST), involved increasing maternal child acceptance and decreasing maternal control (or increasing autonomy granting). Results of the present dissertation findings support the use of all three treatment conditions (ICBT, RLST, RFST) for child anxiety; that is, significant reductions in anxiety were found in each of the three treatment conditions. No significant differences were found between treatment conditions with respect to diagnostic recovery rate, clinician rating, and parent rating of child anxiety. Significant differences between conditions were found on child self rating of anxiety, with some evidence to support the superiority of RLST and RFST to ICBT. These findings support the efficacy of individual, as well as parent involved CBT, and provide mixed evidence with respect to the superiority of parent involved CBT over ICBT. The conceptual, empirical, and clinical implications of the findings are discussed. ^

An Exergy Based Engineering and Economic Analysis of Sustainable Building

To achieve the goal of sustainable development, the building energy system was evaluated from both the first and second law of thermodynamics point of view. The relationship between exergy destruction and sustainable development were discussed at first, followed by the description of the resource abundance model, the life cycle analysis model and the economic investment effectiveness model. By combining the forgoing models, a new sustainable index was proposed. Several green building case studies in U.S. and China were presented. The influences of building function, geographic location, climate pattern, the regional energy structure, and the technology improvement potential of renewable energy in the future were discussed. The building’s envelope, HVAC system, on-site renewable energy system life cycle analysis from energy, exergy, environmental and economic perspective were compared. It was found that climate pattern had a dramatic influence on the life cycle investment effectiveness of the building envelope. The building HVAC system energy performance was much better than its exergy performance. To further increase the exergy efficiency, renewable energy rather than fossil fuel should be used as the primary energy. A building life cycle cost and exergy consumption regression model was set up. The optimal building insulation level could be affected by either cost minimization or exergy consumption minimization approach. The exergy approach would cause better insulation than cost approach. The influence of energy price on the system selection strategy was discussed. Two photovoltaics (PV) systems – stand alone and grid tied system were compared by the life cycle assessment method. The superiority of the latter one was quite obvious. The analysis also showed that during its life span PV technology was less attractive economically because the electricity price in U.S. and China did not fully reflect the environmental burden associated with it. However if future energy price surges and PV system cost reductions were considered, the technology could be very promising for sustainable buildings in the future.

The decolonization of Northwest Community College

In 1996, the authors of the Canadian Royal Commission on Aboriginal Peoples concluded Canadian educational policy had been based on the false assumption of the superiority of European worldviews. The report authors recommended the transformation of curriculum and schools to recognize that European knowledge was not universal. Aboriginal researcher Battiste believes the current system of Canadian education causes Aboriginal children to face cognitive imperialism and cognitive assimilation and that this current practice of cultural racism in Canada makes educational institutions a hostile environment for Aboriginal learners. In order to counter this cultural racism, Battiste calls for the decolonization of education. ^ In 2005, the president of Northwest Community College (NWCC), publicly committed to decolonizing the college in order to address the continuing disparity in educational attainment between Aboriginal and non-Aboriginal learners. Upon the president’s departure in 2010, the employees of NWCC were left to define for themselves the meaning of decolonization. ^ This qualitative study was designed to build a NWCC definition of colonization and decolonization by collecting researcher observations, nine weeks of participant blog postings, and pre and post blog Word survey responses drawn from a purposeful sample of six Aboriginal and six non-Aboriginal NWCC employees selected from staff, instructor and administrator employee groups. The findings revealed NWCC employees held multiple definitions of colonization and decolonization which did not vary between employee groups, or based on participant gender; however, differences were found based on whether the participants were Aboriginal or non-Aboriginal. ^ Both Aboriginal and non-Aboriginal participants thought decolonization was a worthy goal for the college. Aboriginal participants felt hopeful that decolonization would happen in the future and thought decolonization had to do with moving forward to a time when they would be valued, respected, empowered, unashamed, safe, and viewed as equal to non-Aboriginals. Non-Aboriginal participants were unsure if decolonization was possible because it would require going back in time to restore the Aboriginal way of life. When non-Aboriginal participants felt their thoughts were not being valued or they were being associated with colonialism, they felt angry and guarded and were uncomfortable with Aboriginal participants expressing anger towards Colonizers.^

A Research Platform for Artificial Neural Networks with Applications in Pediatric Epilepsy

This dissertation established a state-of-the-art programming tool for designing and training artificial neural networks (ANNs) and showed its applicability to brain research. The developed tool, called NeuralStudio, allows users without programming skills to conduct studies based on ANNs in a powerful and very user friendly interface. A series of unique features has been implemented in NeuralStudio, such as ROC analysis, cross-validation, network averaging, topology optimization, and optimization of the activation function’s slopes. It also included a Support Vector Machines module for comparison purposes. Once the tool was fully developed, it was applied to two studies in brain research. In the first study, the goal was to create and train an ANN to detect epileptic seizures from subdural EEG. This analysis involved extracting features from the spectral power in the gamma frequencies. In the second application, a unique method was devised to link EEG recordings to epileptic and non-epileptic subjects. The contribution of this method consisted of developing a descriptor matrix that can be used to represent any EEG file regarding its duration and the number of electrodes. The first study showed that the inter-electrode mean of the spectral power in the gamma frequencies and its duration above a specific threshold performs better than the other frequencies in seizure detection, exhibiting an accuracy of 95.90%, a sensitivity of 92.59%, and a specificity of 96.84%. The second study yielded that Hjorth’s parameter activity is sufficient to accurately relate EEG to epileptic and non-epileptic subjects. After testing, accuracy, sensitivity and specificity of the classifier were all above 0.9667. Statistical tests measured the superiority of activity at over 99.99 % certainty. It was demonstrated that 1) the spectral power in the gamma frequencies is highly effective in locating seizures from EEG and 2) activity can be used to link EEG recordings to epileptic and non-epileptic subjects. These two studies required high computational load and could be addressed thanks to NeuralStudio. From a medical perspective, both methods proved the merits of NeuralStudio in brain research applications. For its outstanding features, NeuralStudio has been recently awarded a patent (US patent No. 7502763).

Obtenção e caracterização de um compósito polimérico de matriz poliéster e reforço/carga de tecido plano de algodão

He was obtained and studied the feasibility of using TPA (Tissue Cotton Plan) screen type, for bagging, with a weight of 207.9 g / m2 in a composite of orthophthalic crystal polyester resin matrix. The process for obtaining the composite was tested against the maximum number of layers that could be used without compromising the processability and manufacturing of CPs in compression mold. Five configurations / formulations were selected and tested at 1, 4, 8, 10 and 12 layers of cotton tissue - TPA. TPA was not subjected to chemical treatment, only by passing a mechanical washing process. The composite in its various configurations / formulations was characterized to determine its physical properties. The properties of the composite were higher viability resistance to bending, approaching the matrix and impact resistance, superiority in relation to the polyester resin. Another property that has shown good result compared to other composite has water absorption. Analyzing all the properties set the settings / formulations with higher viability were TA8 and TA10, by combining good processability and higher mechanical strength, with lower loss compared to polyester resin matrix. The composite showed lower mechanical behavior of the resin matrix for all the formulations studied except the impact resistance. The SEM showed a good adhesion between the layers of TPA and polyester resin matrix, without the presence of micro voids in the matrix confirming the efficient manufacturing process of the samples for characterization. The composite proposed proved to be viable for the fabrication of structures with low requests from mechanical stresses, and as demonstrated for the manufacture of solar and wind prototypes, and packaging, shelving, decorative items, crafts and shelves, with good visual appearance.