The objective of this study was to (1) measure the concentration of four anions (Cl-, F-, NO and SO ) and nine other elements (Al, Ba, Ca, K, Mg, Mn, Fe, Ni, and Si) in two nontraditional biopolymeric chemical stabilizers (EBCS1 and EBCS2), (2) investigate consequent environmental toxicity risk implications, and (3) create awareness regarding environmental health issues associated with metal concentration levels in enzyme-based chemical stabilizers that are now gaining widespread application in road construction and other concrete materials. Potential ecotoxicity impacts were studied on aqueous extracts of EBCS1 and EBCS2 using two thermodynamic properties models: the Pitzer–Mayorga model (calculation of the electrolyte activity coefficients) and the Millero–Pitzer model (calculation of the ionic activity coefficients). Results showed not only high concentrations of a variety of metal ions and inorganic anions, but also a significant variation between two chemical stabilizing mixtures. The mixture (EBCS2) with the lower pH value was richer in all the cationic and anionic species than (EBCS1). Sulfate ( ) concentrations were found to be higher in EBCS2 than in EBCS1. There was no correlation between electrolyte activity and presence of the ionic species, which may be linked to a possible high ionic environmental activity. The concentrations of trace metals found (Mn, Fe, and Ni) were low compared to those of earth metals (Ba, Ca, K, and Mg). The metal concentrations were higher in EBCS1 than in EBCS2. Data suggest that specific studies are needed to establish “zero” permissible metal ecotoxicity values for elements and anions in any such strong polyelectrolytic enzyme-based chemical stabilizers.

Urea based fertilizers are susceptible to N losses through volatilization, denitrification, and leaching. A field and incubation experiment were conducted at Mississippi State between 2013 and 2015 to evaluate the effect of fertilizer stabilizers on grain yield, N use, and N transformations in various soil textures. Stabilizers were applied to liquid urea-ammonium-nitrate (UAN) solution (32%) and granular urea (46-0-0) at labeled rates for 179 and 112 kg N ha-1 for the field and incubation experiments, respectively. Grain yield and N content at tasseling and physiological maturity were measured for the field experiment. Extracts from the incubation experiment were measured for NH4+-N and NO3⁻-N concentrations. Results from the field experiment suggest greater plant N accumulation, but inconsistent yield increases with fertilizer stabilizers. Incubation results indicate fertilizer stabilizers significantly decrease the rate of N transformations. Further research is necessary to determine the effects of stabilizers over N rates and yearly environmental conditions.

Nitrile containing siloxane block copolymers were developed as stabilizers for siloxane magnetic fluids. The siloxane magnetic fluids have been recently proposed as internal tamponades for retinal detachment surgery. PDMS-b-PCPMS-b-PDMSs (PDMS = polydimethylsiloxane, PCPMS = poly(3-cyanopropylmethylsiloxane) were successfully prepared through kinetically controlled polymerization of hexamethylcyclotrisiloxane initiated by lithium silanolate endcapped PCPMS macroinitiators. The macroinitiators were prepared by equilibrating mixtures of 3- cyanopropylmethylcyclosiloxanes (DxCN) and dilithium diphenylsilanediolate (DLDPS). DxCNs were synthesized by hydrolysis of 3-cyanopropylmethyldichlorosilane, followed by cyclization and equilibration of the resultant hydrolysates. DLDPS was prepared by deprotonation of diphenylsilanediol with diphenylmethyllithium. It was found that mixtures of DxCN and DLDPS could be equilibrated at 100°C within 5-10 hours. By controlling the DxCN-to-DLDPS ratio, macroinitiators of different molecular weights could be obtained. The major cyclics in the macroinitiator equilibrate are tetramer (8.6 ± 0.7 wt%), pentamer (6.3 ± 0.8 wt%) and hexamer (2.1 ± 0.5 wt%). 2.5k-2.5k-2.5k, 4k-4k-4k, and 8k-8k-8k triblock copolymers were prepared and characterized. These triblock copolymers are transparent, microphase separated and highly viscous liquids. It was found that these triblock copolymers can stabilize nanometer gamma-Fe₂O₃ and cobalt particles in octamethylcyclotetrasiloxane or hexane. Hence PDMS-b-PCPMS -b-PDMSs represent a class of promising steric stabilizers for silicone magnetic fluids. / Master of Science

The loss and recovery of the surface hydrophobicity areimportant phenomena when highvoltage insulators, with a shedmaterial composed of polydimethylsiloxane (PDMS), are used. Theloss of hydrophobicity is mostly due to the oxidativecrosslinking which takes place on the PDMS surface duringexposure to electrical discharges, e. g. corona discharges. Thecrosslinking reaction leads to the formation of anoxygen-enriched, silica-like layer, which is brittle and henceprone to cracking, either spontaneously or upon mechanicaldeformation. Repetitive cracking leads to the propagation ofcracks into the core of the material, which is believed todeteriorate the insulator’s performance and reduce itsservice-life. Hence, an approach to make PDMS more resistant tothe build-up of the silica-like layer is beneficial for theperformance of PDMS in high voltage insulators. In this work the effect of antioxidative stabilizers on thecorona- and air-plasma-induced surface oxidation of PDMS isstudied. Three commercial stabilizers, a hindered phenol(Irganox® 1076), a hindered amine light stabilizer(Tinuvin® 770) and a bifunctional stabilizer withchainbreaking hindered phenol and secondary amine andhydroperoxide-decomposing sulfide moieties (Irganox® 565),have been used. Surface oxidation was achieved by exposure of amodel crosslinked PDMS to an air plasma or a corona discharge,and the surface characteristics of the exposed samples wereassessed by contact angle measurements, X-ray photoelectronspectroscopy, optical and scanning electron microscopy, andsurface profilometry before and after uniaxial stretching. A reliable rapid method for the assessment of stabilizerconcentration in PDMS was established. PDMS samples containingknown stabilizer concentrations of a phenolic antioxidant(Irganox® 1010) and a hindered amine stabilizer(Tinuvin® 144) were prepared. It was shown that thestabilizer concentration in PDMS could be determined by highperformance liquid chromatography (HPLC) of the microwaveassisted solvent extracts (MAE) of stabilized PDMS samplesusing acetone (a non-swelling solvent). This method wasemployed to measure the stabilizer concentration in PDMSsamples exposed to air plasma and corona discharges. Thestabilizer concentration in PDMS was varied by using diluteswelling solutions (0.005 wt% to 0.2 wt%) of the stabilizers inhexane. Samples stabilized with Irganox 565 showed stabilizerprecipitation on the surface after swelling in solutions with astabilizer concentration greater than 0.05 wt%. Samplescontaining Irganox 1076 and Tinuvin 770 showed no surfaceprecipitation except after swelling in a solution of 0.2 wt%stabilizer concentration. The air plasma and corona exposure time required for theformation of the silica-like surface layer increased,essentially, in a linear fashion with increasing stabilizerconcentration. Tinuvin 770 showed the strongest overallprotecting effect during, as well air plasma as coronaexposures, whereas Irganox 565 showed the strongest protectingeffect per mass fraction stabilizer during air plasmaexposures. Irganox 1076 was of moderate efficiency. The resultssuggest that efficient protection towards discharge-inducedsurface oxidation is achieved with hindered amine stabilizersor with stabilizers combining chain-breaking andhydroperoxide-decomposing functions. The diffusion of the stabilizers Irganox 1010 and Tinuvin144 from PDMS to water at elevated temperatures (75 °C and95 °C for Irganox 1010 and 95 °C for Tinuvin 144) wasstudied. For Irganox 1010 the diffusion constant (D), accordingto Fick’s second law for uni-dimensional penetrantdiffusion was assessed to 3.1 X 10-9cm2s-1at 95 °C and to 5.46 X 10-10cm2s-1at 75 °C. An estimate for the activationenergy for the diffusion of Irganox 1010 to the surroundingmedia was obtained (Ea=93 kJ mol-1), on the basis of the diffusion data. For Tinuvin144, no diffusion constant could be calculated due to poorseparation of the stabilizer peak from the impurities in theextract when using the HPLC method developed earlier.

<p>The loss and recovery of the surface hydrophobicity areimportant phenomena when highvoltage insulators, with a shedmaterial composed of polydimethylsiloxane (PDMS), are used. Theloss of hydrophobicity is mostly due to the oxidativecrosslinking which takes place on the PDMS surface duringexposure to electrical discharges, e. g. corona discharges. Thecrosslinking reaction leads to the formation of anoxygen-enriched, silica-like layer, which is brittle and henceprone to cracking, either spontaneously or upon mechanicaldeformation. Repetitive cracking leads to the propagation ofcracks into the core of the material, which is believed todeteriorate the insulator’s performance and reduce itsservice-life. Hence, an approach to make PDMS more resistant tothe build-up of the silica-like layer is beneficial for theperformance of PDMS in high voltage insulators.</p><p>In this work the effect of antioxidative stabilizers on thecorona- and air-plasma-induced surface oxidation of PDMS isstudied. Three commercial stabilizers, a hindered phenol(Irganox® 1076), a hindered amine light stabilizer(Tinuvin® 770) and a bifunctional stabilizer withchainbreaking hindered phenol and secondary amine andhydroperoxide-decomposing sulfide moieties (Irganox® 565),have been used. Surface oxidation was achieved by exposure of amodel crosslinked PDMS to an air plasma or a corona discharge,and the surface characteristics of the exposed samples wereassessed by contact angle measurements, X-ray photoelectronspectroscopy, optical and scanning electron microscopy, andsurface profilometry before and after uniaxial stretching.</p><p>A reliable rapid method for the assessment of stabilizerconcentration in PDMS was established. PDMS samples containingknown stabilizer concentrations of a phenolic antioxidant(Irganox® 1010) and a hindered amine stabilizer(Tinuvin® 144) were prepared. It was shown that thestabilizer concentration in PDMS could be determined by highperformance liquid chromatography (HPLC) of the microwaveassisted solvent extracts (MAE) of stabilized PDMS samplesusing acetone (a non-swelling solvent). This method wasemployed to measure the stabilizer concentration in PDMSsamples exposed to air plasma and corona discharges. Thestabilizer concentration in PDMS was varied by using diluteswelling solutions (0.005 wt% to 0.2 wt%) of the stabilizers inhexane. Samples stabilized with Irganox 565 showed stabilizerprecipitation on the surface after swelling in solutions with astabilizer concentration greater than 0.05 wt%. Samplescontaining Irganox 1076 and Tinuvin 770 showed no surfaceprecipitation except after swelling in a solution of 0.2 wt%stabilizer concentration.</p><p>The air plasma and corona exposure time required for theformation of the silica-like surface layer increased,essentially, in a linear fashion with increasing stabilizerconcentration. Tinuvin 770 showed the strongest overallprotecting effect during, as well air plasma as coronaexposures, whereas Irganox 565 showed the strongest protectingeffect per mass fraction stabilizer during air plasmaexposures. Irganox 1076 was of moderate efficiency. The resultssuggest that efficient protection towards discharge-inducedsurface oxidation is achieved with hindered amine stabilizersor with stabilizers combining chain-breaking andhydroperoxide-decomposing functions.</p><p>The diffusion of the stabilizers Irganox 1010 and Tinuvin144 from PDMS to water at elevated temperatures (75 °C and95 °C for Irganox 1010 and 95 °C for Tinuvin 144) wasstudied. For Irganox 1010 the diffusion constant (D), accordingto Fick’s second law for uni-dimensional penetrantdiffusion was assessed to 3.1 X 10^-9cm²s^-1at 95 °C and to 5.46 X 10^-10cm²s^-1at 75 °C. An estimate for the activationenergy for the diffusion of Irganox 1010 to the surroundingmedia was obtained (E_a=93 kJ mol^-1), on the basis of the diffusion data. For Tinuvin144, no diffusion constant could be calculated due to poorseparation of the stabilizer peak from the impurities in theextract when using the HPLC method developed earlier.</p>

Abstract Bipolar disorder is a complex illness. It is a life long episodic disorder very disruptive for the patient and family. Repeated episodes lead to progressively deteriorating level of functioning and poor response to the treatment. Suicide attempts and completed suicide has been a frequent complication. The complexity and difficulties involved in treating this mental condition are well recognised .The pharmacological options include lithium, valproate, carbamazepine, lamotrigine, topiramate, benzodiazepines. The use of neuroleptics in bipolar disorder remain controversial because of the increased susceptibility of this group of patients to side effects of neuroleptics. Objectives: The aim of this research is to investigate in a population of patients with bipolar disorder who are having treatment with combination of a mood stabilizer and antipsychotics: 1) The number of prescriptions of antipsychotics, in bipolar patients in a community clinic 2) The rationale of such combination 3) Whether correlates exist between variables such as substance abuse and noncompliance and the prescription of antipsychotics Method: This retrospective, descriptive, analytic study was conducted at Voslooros Psychiatric Clinic, which is situated in the south of Johannesburg. The clinical records of all adult patients with an initial diagnosis of bipolar disorder as at December 2004 were examined Particular note was taken of demographic data, diagnosis, age of onset of psychiatric illness, V duration of illness, treatment prescribed, reasons for prescribing this medication, response to the treatment, social circumstances of each patient, substances use and compliance. Results: 74.1% of the patients were maintained on a combination of mood stabilizer with antipsychotic. Combination treatment was used in an attempt to improve the psychotic symptoms and dangerous behaviour in 48% of the patients, noncompliance in 38% of the cases and 14% patients were in transitional phase to stop antipsychotics. 80.65% of the patients were on treatment with antipsychotics for longer than 6 months. Use of atypical antipsychotics is associated with a better outcome than the conventional agents. In this study only a small percentage (10 %) of patients received atypical antipsychotics. 19.4 % patients reported side effects of the medication. The lower figures in our study can be due to underreporting and inadequate documentation. . 38.7% of the patients reported substance misuse. Our finding were much lower compared with the literature, probably due to underreporting. Alcohol was the most common substance. This study show that the need for more medication was increased 6.6 fold in patients with polysubstance abuse compared with the patients not abusing any substance. Noncompliance in the maintenance phase of the treatment is a important issue in the management of the patients with bipolar disorder. This study found that the majority of the patients (59.7%) were noncompliant with their treatment. Those findings were in line with studies done by Keck PE who reported rates of noncompliance from 51% to 64%. Our study show that 63% of the patients had a level of VI education less than matric and this may be a contributing factor to noncompliance. Conclusions: The results of the study suggest that a large number of bipolar patients are only partially responsive to mood stabilizers alone and the maintenance treatment with antipsychotics for longer than 6 months are needed because of persistence of the symptoms. More efficient strategies are necessary to educate the people, to improve the compliance and to decreased the use of substances.

Class of 2009 Abstract / Objectives: This study utilized a prescription claims database to retrospectively assess the relationship between adherence rates with a mood stabilizer in bipolar type I patients for: gender, age, psychiatric hospitalization rates, cost of services, and concomitant psychotropic medications. Methods: Adult patients with bipolar type I disorder (N=149; F=92 and M=57) who received at least two prescriptions of a mood stabilizer (i.e., carbamazepine, lamotrigine, lithium, oxcarbazepine, and valproic acid) during a 3-month intake period were included. Adherence to the mood stabilizer was retrospectively analyzed using high: >75% (> 274 days) vs. low: < 75% (< 274 days) supply of a mood stabilizer during 12-months. Results: Only 35.6% of the patients (N=53) met the criteria for > 75% adherence and 11.4% (N=17) met the criteria for > 90% adherence. There was a trend toward women having more days supply of a mood stabilizer compared to men (p=0.08) and older patients having a higher adherence rate with a mood stabilizer (p=0.06). The high adherence group had greater prescription costs (p<0.001) and total cost per year (R2=0.34, p=0.064) and more concomitant medications (p=0.04) than the low adherence group. Overall, there were no significant differences between the high and low adherence groups for mean hospital days, inpatient costs, and total cost of care. Among those patients that were hospitalized there was a negative correlation between adherence and inpatient cost (R2=0.49, p=0.024). Conclusions: Our findings suggest that patients with bipolar type I disorder demonstrate poor medication adherence with a mood stabilizer and that adherence rates based on a prescription claims database using two adherence categories may not be a predictive factor for psychiatric hospitalizations or cost of care.

Title of thesis: Polymeric stabilizers maintaining the saturation solubility of itraconazole nanocrystals after dissolution process Author: Jana Kubačková Department: Pharmaceutical Technology Supervisor: PharmDr. Ondřej Holas, Ph.D. Specialized supervisor: Assoc. Prof. Leena Peltonen, Ph.D. The increase of bioavailability of poorly water soluble drugs is still an issue. One of the techniques improving aqueous drug substance solubility, and consequently enhancing bioavailability, is formation of nanoparticles. However, the bioavailability is determined by the concentration of the dissolved drug achieved at the time of absorption. This fact emphasizes the importance of the maintenance of the high solubility until the absorption area is reached. Sufficiently stabilised nanocrystalline drugs offer a solution to this problem. In this thesis, the solid nanoparticle formations of an antifungal agent itraconazole (ITZ) are presented. Wet milling was employed to create the nanosuspension stabilised by binary mixture of stabilisers or by a single stabiliser. An aggregation inhibitor Poloxamer 407 (F127) in the combination with a polymeric precipitation inhibitor hydroxypropyl methylcellulose (HPMC) or polyvinyl pyrrolidone (PVP) at different ratios, or a single precipitation inhibitor, were utilised. The...

This thesis concerns infinite words over finite alphabets. It contributes to two topics in this area: critical exponents and stabilizers. Let w be a right-infinite word defined over a finite alphabet. The critical exponent of w is the supremum of the set of exponents r such that w contains an r-power as a subword. Most of the thesis (Chapters 3 through 7) is devoted to critical exponents. Chapter 3 is a survey of previous research on critical exponents and repetitions in morphic words. In Chapter 4 we prove that every real number greater than 1 is the critical exponent of some right-infinite word over some finite alphabet. Our proof is constructive. In Chapter 5 we characterize critical exponents of pure morphic words generated by uniform binary morphisms. We also give an explicit formula to compute these critical exponents, based on a well-defined prefix of the infinite word. In Chapter 6 we generalize our results to pure morphic words generated by non-erasing morphisms over any finite alphabet. We prove that critical exponents of such words are algebraic, of a degree bounded by the alphabet size. Under certain conditions, our proof implies an algorithm for computing the critical exponent. We demonstrate our method by computing the critical exponent of some families of infinite words. In particular, in Chapter 7 we compute the critical exponent of the Arshon word of order n for n ≥ 3. The stabilizer of an infinite word w defined over a finite alphabet Σ is the set of morphisms f: Σ*→Σ* that fix w. In Chapter 8 we study various problems related to stabilizers and their generators. We show that over a binary alphabet, there exist stabilizers with at least n generators for all n. Over a ternary alphabet, the monoid of morphisms generating a given infinite word by iteration can be infinitely generated, even when the word is generated by iterating an invertible primitive morphism. Stabilizers of strict epistandard words are cyclic when non-trivial, while stabilizers of ultimately strict epistandard words are always non-trivial. For this latter family of words, we give a characterization of stabilizer elements. We conclude with a list of open problems, including a new problem that has not been addressed yet: the D0L repetition threshold.

This thesis concerns infinite words over finite alphabets. It contributes to two topics in this area: critical exponents and stabilizers. Let w be a right-infinite word defined over a finite alphabet. The critical exponent of w is the supremum of the set of exponents r such that w contains an r-power as a subword. Most of the thesis (Chapters 3 through 7) is devoted to critical exponents. Chapter 3 is a survey of previous research on critical exponents and repetitions in morphic words. In Chapter 4 we prove that every real number greater than 1 is the critical exponent of some right-infinite word over some finite alphabet. Our proof is constructive. In Chapter 5 we characterize critical exponents of pure morphic words generated by uniform binary morphisms. We also give an explicit formula to compute these critical exponents, based on a well-defined prefix of the infinite word. In Chapter 6 we generalize our results to pure morphic words generated by non-erasing morphisms over any finite alphabet. We prove that critical exponents of such words are algebraic, of a degree bounded by the alphabet size. Under certain conditions, our proof implies an algorithm for computing the critical exponent. We demonstrate our method by computing the critical exponent of some families of infinite words. In particular, in Chapter 7 we compute the critical exponent of the Arshon word of order n for n ≥ 3. The stabilizer of an infinite word w defined over a finite alphabet Σ is the set of morphisms f: Σ*→Σ* that fix w. In Chapter 8 we study various problems related to stabilizers and their generators. We show that over a binary alphabet, there exist stabilizers with at least n generators for all n. Over a ternary alphabet, the monoid of morphisms generating a given infinite word by iteration can be infinitely generated, even when the word is generated by iterating an invertible primitive morphism. Stabilizers of strict epistandard words are cyclic when non-trivial, while stabilizers of ultimately strict epistandard words are always non-trivial. For this latter family of words, we give a characterization of stabilizer elements. We conclude with a list of open problems, including a new problem that has not been addressed yet: the D0L repetition threshold.