The occurrence of Pharmaceuticals and Personal Care Products (PPCPs) in surface waters has become a growing concern within the last decade although the first mention of human PPCPs in the environment goes back to late 1970s. Pharmaceuticals include prescription drugs, over-the-counter medications, and veterinary drugs. Personal care products include products such as lotions, fragrances, and soaps. In addition to traditional personal care products, the term PPCPs has been adopted to represent a wide variety of chemicals used in consumer products including plasticizers and fire retardants. Wastewater effluents are thought to be the main source of PPCPs in surface waters since most pharmaceuticals and personal care products eventually are disposed of, directly or indirectly, into domestic sewage systems that are not specifically designed to treat them. This thesis research examined the occurrence and removal of ten PPCPs in three Utah wastewater treatment plants (WWTPs) in the State of Utah. The ten PPCPs (caffeine, acetaminophen, sulfamethoxazole, tris(2-chloroethyl) phosphate, carbamazepine, estrone, progesterone, gemfibrozil, 4-n-nonylphenol, and bis(2- ethylhexyl) phthalate) were selected for this study based on their chemical properties, environmental concern due to their widespread use, frequent detection in natural water, wastewater, and biosolids, and potential risk to the environmental and human health. The selected treatment technologies, represented by Brigham, Hyrum, and Spanish Fork WWTPs, were oxidation ditches, membrane bioreactors, and trickling filters. Influent, effluent and biosolids samples were collected in May, July, and August of 2011. The highest influent concentrations were measured for caffeine (3.9 – 15.4 μg/L) and acetaminophen (7.4 – 71.5 μg/L). Sulfamethoxazole, tris(2-chloroethyl) phosphate, and carbamazepine were measured in the effluent of all three WWTPs. Removal efficiencies calculated from differences between influent and effluent concentrations were caffeine (>80%), acetaminophen (>99%), and sulfamethoxazole (>60%). Tris(2-chloroethyl) phosphate, carbamazepine, and bis(2-ethylhexyl) phthalate were not consistently found above the method limits of quantitation (LOQs). The effluent concentrations of the measured PPCPs were below the levels of concern suggested by available toxicity data.

The synthesis or the interaction between two or more molecules is known as supramolecular chemistry. The concept of supramolecular chemistry can be applied to the design of new pharmaceutical materials affording new compositions of matter with desirable composition, structure and properties. The design of a two-molecule, or binary, compound using complementary molecules represents an example of an application of crystal engineering. Crystal engineering is the understanding of intermolecular interactions, in the context of crystal packing, in the design of new solid materials. By identifying reliable connectors through molecular recognition or self-assembly, one can build predictable architectures. The study of supramolecular synthesis was accomplished using known pharmaceutical molecules such as Nifedipine (calcium channel blocker used for cardiovascular diseases) and Phenytoin (used as an anticonvulsant drug) and model compounds containing synthons common in pharmaceutical drugs (Crown ethers and Trimesic acid with ether linkages and carboxylic acid dimers, respectively) with complementary molecular additives. The co-crystals formed were characterized by various techniques (IR, m.p., XPD, single X-ray diffraction) and preliminary results were found to exhibit characteristics different from the parent compounds as a direct result of hydrogen bonding and self-assembly interactions. These crystalline assemblies could afford improved solubility, dissolution rate, stability and bioavailability.

L’objectif de la thèse vise à déterminer les facteurs et processus qui contrôlent l’origine et la qualité des eaux souterraines alluviales et ainsi à mieux comprendre le fonctionnement et la vulnérabilité des aquifères alluviaux qui occupent une place prééminente dans le paysage hydrogéologique mondial tant pour leur rôle économique - production d'eau potable, développement agricole - que pour leur rôle écologique. Des mesures hydrodynamiques, hydrochimiques (ions majeurs, traces, molécules phytosanitaires et pharmaceutiques) combinées à des déterminations isotopiques (oxygène-18, deuterium, carbone-13) ont ainsi été effectuées sur 19 points incluant puits, piézomètres et eaux de surface, de février 2011 à novembre 2012, afin d’évaluer l’origine et la qualité de l’eau souterraine dans l’aquifère alluvial de la rivière Allier, un des principaux tributaires de la Loire. La zone d’étude, située près de la ville de Clermont-Ferrand (France), joue par ailleurs un rôle socio-économique majeur, la nappe alluviale de l’Allier constituant la principale ressource en eau potable pour une population d’environ 100 000 habitants. D’un point de vue hydrodynamique, l'eau souterraine circule généralement du sud au nord, avec une alimentation naturelle à partir des coteaux adjacents, dans la partie non-pompée de l'aquifère. Dans la zone de pompage, cette circulation naturelle est modifiée par le pompage qui fait pénétrer l’eau de la rivière Allier dans l’aquifère. La recharge de l’aquifère dépend alors de quatre pôles de mélange : pluie, rivière Allier, coteaux adjacents et partie sud, non-pompée, de l’aquifère. Les résultats chimiques et isotopiques obtenus permettent de cartographier la contribution de chaque pôle de mélange. [...] Ces résultats mettent en évidence la vulnérabilité de l’aquifère face aux pollutions. Les parties méridionale et orientale du site sont affectées par des arrivées d’eaux de qualité médiocre démontrant l’importance de la définition d’un périmètre de protection adaptée. Près de l’Allier, une attention particulière doit être portée non seulement aux pollutions ponctuelles qui peuvent se produire sur le cours de la rivière, mais également aux pollutions chroniques liées notamment aux rejets des stations d’épuration pourvoyeurs de polluants tels les molécules pharmaceutiques. Toutes les informations acquises devront être incluses dans les stratégies de gestion d'eau souterraine afin protéger la durabilité de cette ressource de valeur. Les résultats s’appuient sur les investigations menées sur la nappe alluviale de l’Allier, néanmoins la méthodologie utilisée et sa transposition à des systèmes analogues est l’une des perspectives majeures de cette étude. / Hydrodynamic, hydrochemical (major ions, traces, pharmaceuticals and pesticides), and isotopic investigations (oxygen-18 and deuterium) were carried out on 19 points, including boreholes, piezometer, surface water, and springs from February 2011 to November 2012, to assess groundwater quality in the unconfined shallow alluvial aquifer of the Allier River (one of the main tributary of the Loire River). The study area, located near the city of Clermont-Ferrand (France), plays an important socio-economic role as the alluvial aquifer is the major source of drinking water for about 100 000 inhabitants. The objective of the project aims at understanding the functioning and the vulnerability of alluvial aquifers that occupy a pre-eminent position in the hydrogeologic landscape both for their economic role - production of drinking water and agricultural development - and for their ecological role. Moreover, this study also targets at determining the factors and processes controlling shallow groundwater quality and origin. The water circulates from the south, with a natural alimentation from the hills in the non-pumped part of the alluvial aquifer. In the pumping zone, this general behaviour is altered by the pumping that makes the water from the Allier River enter the system in a large proportion. Four end-members have been identified for the recharge of the alluvial groundwater: rainfall, Allier River, surrounding hills’ aquifer and the southern non-pumped part of the alluvial system. Results indicate that, despite the global Ca-HCO3 water type of the groundwater, spatial variations of physico-chemical parameters do exist in the study area. Ionic concentrations increase from the Allier River towards east due either to the increase in the residence time or a mixing with groundwater coming from the aquifer’s borders. Stable isotopes of the water molecule show the same results: boreholes close to the river bank are recharged by the Allier River (depleted values), while boreholes far from the river exhibit isotopic contents close to the values of hills’ spring or to the southern part of the alluvial aquifer, both recharged by local precipitation. One borehole (B65) does not follow this scheme of functioning and presents values attesting of a probable sealing of the Allier River banks. Based on these results, the contribution of each end-member has been calculated and the functioning of the alluvial system determined. According to this general scheme of functioning, origins of pollution (agricultural, urban) have been determined and clues to the protection of such hydrosystems defined.

This thesis consists of three independent essays, unified by the common theme of the distributional impacts of government. The first paper estimates the price elasticity of demand for pharmaceuticals amongst high-income older people in Australia. It exploits a natural experiment by which some people gained entitlement to a price reduction through the Commonwealth Seniors Health Card (CSHC). The preferred model is a nonlinear Instrumental Variable (IV) difference-in-difference regression, estimated on repeated cross sectional survey data using the Generalised Method of Moments. No significant evidence is found for endogenous card take-up, and so cross-sectional estimates are also considered. Taking all of the results and possible sources of bias into account, the ??headline?? estimate is -0.1, implying that quantity demanded is not highly responsive to price. The elasticity estimate is a key input into the second paper which analyses the distributional impact of the CSHC. I consider the trade-off between moral hazard and risk pooling. There have been few previous attempts internationally to address this trade-off empirically for any health insurance scheme. The utility gain through risk-pooling is found to be negligible. However, the deadweight loss through moral hazard may be considerable. I also use an illustrative model to demonstrate the possible effects of the CSHC on inter-temporal savings behaviour. While the CSHC may induce some people to save, it may have the opposite effect on others. The net impact was not determined. The third paper estimates the Australian public sector wage premium. It includes a detailed critical review of the methods available to address this issue. The chosen approach is a quasi-differenced panel data model, estimated by nonlinear IV, which has many advantages over other methods and has not been used before for this topic. I find a positive average public sector wage premium for both sexes. The best estimates are 10.0% for men and 7.1% for women. The estimate for men is statistically significant (p < 0.04) and borders on significance for women (p < 0.07). No evidence is found to suggest that the public sector has an equalising effect on the wages of its workers.

<p>Problem:</p><p>The problem under consideration is the World Trade Organization’s (WTO) agreement called Trade-Related Aspects of Intellectual Property Rights (TRIPS) and its impact on equal access to essential drugs in the least developed countries. Especially the countries of sub-Saharan Africa lack such access. Moreover, these countries are the ones where severe diseases like AIDS/HIV, tuberculosis and malaria are widely spread over the population. The authors focus also on patents and their obligatory length imposed through the articles of TRIPS agreement.</p><p>Purpose:</p><p>The purpose of the thesis is to describe and analyse the impact of global trade regulations (TRIPS in particular) on the accessibility of essential drugs in developing countries, and to come up with a possible solution as the way of coping with the problem is concerned. The investigation includes detailed description of solutions accomplished by Brazil and India, and their importance for the least developed countries, in terms of importing generic pharmaceuticals from these.</p><p>Method:</p><p>Qualitative method was used in order to obtain data from interviews with citizens of Botswana, Ghana, Ethiopia and South Africa for better understanding of the situation in these countries. Furthermore, the theories included in the theoretical background of this paper were gathered through deep research in the field of studies regarding Intellectual Property protection and World Trade Organization’s agreements and other legal acts.</p><p>Results:</p><p>The result of the analysis is a model developed from the Game-Theoretic Model, and called Developed Game-Theoretic Model. It is a tool which the least developed countries can use while negotiating prices of medicines with pharmaceutical companies, having the possibility of importing the pharmaceuticals from other countries manufacturing the patented product under compulsory licensing.</p>

No description available.

This study addresses the fundamentals of an important degradation pathway of storing protein pharmaceuticals in an aqueous formulation, oxidation of methionine residues by peroxides. First, a mechanism by which methionine residues are oxidized is identified via ab initio calculations. The major difference of this new mechanism to previous ones is the role of solvent molecules in the oxidation process. Previously proposed mechanisms suggested that solvent molecules facilitate the transfer of hydrogen associated with the oxidation reaction, but the estimated activation energies and pH dependence of oxidation rates derived from this mechanism rates do not agree with experimental observations. In our proposed mechanism, however, water molecules stabilize the charge separation in the transition-state complex through specific interaction such as hydrogen bonding. This mechanism satisfies all experimental studies on the oxidation of organic sulfides by peroxides. A correct picture of instability mechanism is essential in developing stabilization strategies to design a robust formulation. Based on this mechanism, a structure/instability relationship is built to explain the oxidation rates of methionine residues in a protein molecule. Specifically, a structural property, two-shell water coordination number, is found to correlate semi-quantitatively to the rates of oxidation of methionine residues in G-CSF (granulocyte colony-stimulating factor) and hPTH (human parathoid hormone). We also show that a traditionally used structural property, solvent accessible area, can not provide such accurate correlation and that the dynamic motion of protein molecules and an explicit treatment of solvent molecules are essential to describe the rates of oxidation of methionine residues. Furthermore, the insight provided by the molecule-level understanding in developing a stabilizing formulation is discussed. / Singapore-MIT Alliance (SMA)

The study takes its point of departure in a widespread notion that decisions should be based on the ‘facts of the matter’. Normative theories of organizational choice, in particular, encourage organizations to base decisions on facts. Many organizations also face explicit requirements to justify their decision-making with factual knowledge. But what if ‘the facts’ are ambiguous? How do organizations make justifiable decisions with ambiguous knowledge? A study of efforts on the part of the Swedish Pharmaceutical Benefits Board to decide whether prescription drugs are ‘reasonable’ to subsidize, suggests that organizations can employ various methods to remove ambiguity of knowledge. However, such attempts at achieving coherent knowledge on which to base decisions often fail. In these cases, though a decision can be made, the choice of one future action to the exclusion of others is delegated – along with the unresolved ambiguity of knowledge. Thus, the study argues that rationalistic demands for ‘knowledgeable’ and ‘justifiable’ decision outcomes, when taken seriously, make it difficult to make choices. Such demands lead to more decisions and fewer choices, since the difficulty in achieving coherence between multiple knowledge claims will delegate the actual choices to practice. Knowledge-based decision-making could therefore tend to be conservative vis-à-vis the practices that it seeks to control. This has, for instance, implications for the possibility of using ‘evidence-based policy-making’ as a means of setting priorities in healthcare. / Diss. Stockholm : Handelshögskolan i Stockholm, 2006

Problem: The problem under consideration is the World Trade Organization’s (WTO) agreement called Trade-Related Aspects of Intellectual Property Rights (TRIPS) and its impact on equal access to essential drugs in the least developed countries. Especially the countries of sub-Saharan Africa lack such access. Moreover, these countries are the ones where severe diseases like AIDS/HIV, tuberculosis and malaria are widely spread over the population. The authors focus also on patents and their obligatory length imposed through the articles of TRIPS agreement. Purpose: The purpose of the thesis is to describe and analyse the impact of global trade regulations (TRIPS in particular) on the accessibility of essential drugs in developing countries, and to come up with a possible solution as the way of coping with the problem is concerned. The investigation includes detailed description of solutions accomplished by Brazil and India, and their importance for the least developed countries, in terms of importing generic pharmaceuticals from these. Method: Qualitative method was used in order to obtain data from interviews with citizens of Botswana, Ghana, Ethiopia and South Africa for better understanding of the situation in these countries. Furthermore, the theories included in the theoretical background of this paper were gathered through deep research in the field of studies regarding Intellectual Property protection and World Trade Organization’s agreements and other legal acts. Results: The result of the analysis is a model developed from the Game-Theoretic Model, and called Developed Game-Theoretic Model. It is a tool which the least developed countries can use while negotiating prices of medicines with pharmaceutical companies, having the possibility of importing the pharmaceuticals from other countries manufacturing the patented product under compulsory licensing.

Previous research indicates that pharmaceutically active compounds (PhACs) and endocrine-disrupting compounds (EDCs) are poorly removed during conventional drinking water treatment processes including coagulation; however, removal efficiency increases in the presence of natural organic matter (NOM). Therefore, this project investigates the link between various NOM types with EDC/PhAC removal. Bench-scale coagulation tests were conducted on three different source waters spiked with environmentally relevant levels (nominally 1000 ng/L) of EDCs/PhACs. Two different coagulants were used: polyaluminum chloride (PACl) and aluminum sulphate (alum). NOM was characterized using size exclusion liquid chromatography-organic carbon detection (LC-OCD). Results for Lake Ontario, Otonabee and Grand River water indicate that certain EDCs/PhACs are significantly removed during coagulation while others increase in concentration. Concurrently, particular NOM fractions (biopolymers and humic substances) are also being removed. Solvents used for EDC/PhAC spiking (acetone and acetonitrile) did not affect coagulation, but contributed to low molecular weight neutral and hydrophobic NOM fractions.