The cow/calf phase of production represents a large expense in the production of beef, and efficient beef cows use fewer resources to obtain the same outcome in a sustainable environment. The objective of study 1 was to utilize a mechanistic nutrition model to estimate metabolizable energy requirement (MER) of grazing cows based on changes in cow body weight (BW) and fatness measurements (body condition score, BCS) along with calf age and BW, as well as forage quality and quantity. In addition, an energy efficiency index (EEI), computed as MER of the cow and calf divided by calf weaning BW, was used to rank cows within a herd based on their efficiency of utilizing available forage to meet their maintenance requirements and support calf growth. Data were collected from one herd of approximately 140 Santa Gertrudis cows over a four-year period, and analyzed per calving cycle, conception to weaning. The model's estimation of EEI appears to be moderately heritable and repeatable across years, and efficient cows might have greater peak milk and be leaner. In typical feedlot diets, the rates of ruminal fermentation of highly processed grains and the hydrolysis rate of urea may not match. Asynchronous utilization of carbohydrate and protein would result in some portion of the urea unknot being utilized by the ruminal microbes and ultimately the animal. The use of slow-release urea (SRU) products offers a unique opportunity to synchronize ruminal fermentation of carbohydrate with non-protein nitrogen (NPN) release rate. Two experiments were conducted to examine the impact of source, urea or SRU, and level of dietary NPN on 1) performance and carcass characteristics and 2) N balance of finishing cattle. Steers had lower initial F:G when SRU was used as the only source of feed N (treatment 3), suggesting that SRU may replace both NPN and true protein feeds in finishing cattle diets. High levels of either NPN source had greater N intake and urinary N excretion, as well as N absorption and no major differences were observed between SRU and urea, suggesting that SRU can replace urea at different levels of N intake.

Large infected bone defects (IBD) are very complicated to treat due to their high variability; they often require multiple procedures. Bone autografts are the gold standard for treatment but have several drawbacks, such as a need for a second surgery site, limited grafting material, and donor site morbidity. The objective of this research was to develop a moldable synthetic bone grafting material capable of releasing both antimicrobial and osteogenic drugs over a clinically relevant time course for the treatment of IBDs. Current treatment methods for large IBDs require two separate procedures to treat the bone defect and the infection. This research sought to combine these two procedures into one implantable composite bone graft substitute for the treatment IBDs. To begin, the degradation and mechanical properties of the calcium sulfate (CS) based composite material were evaluated for different compositions. Next, the controlled drug release profiles from the composite was achieved by using a shell and core system incorporating poly(lactic-co-glycolic acid) microspheres (PLGAms). The release of vancomycin from the shell began immediately and continued over the course of 6 weeks, while the release of simvastatin from the core was delayed before being released over 4 weeks. Next, an infected, critically-sized rat femoral defect model was used to test different treatment methods with and without the composite bone graft substitute. Animals treated with locally released antibiotics had survivorship rates 24% higher than those treated with systemic antibiotics, and animals that received both antibiotics and an osteogenic drug had an increased amount of bone formation at 12 weeks compared to controls. Finally, several different anti-biofilm agents were evaluated for their ability to inhibit and/or disrupt the growth of Staphylococcus aureus (S. aureus) biofilms in vitro. Lysostaphin was the only drug investigated that was able to both inhibit and disrupt S. aureus biofilms. Furthermore, lysostaphin encapsulated into PLGAms maintained its bioactivity and may be useful for future incorporation into biofilm-combating materials. The bone grafting material developed here can be used to locally deliver drugs in a temporally controlled manner to reduce the number of procedures necessary for the treatment of complex IBDs.

Controlled release formulations deliver an active ingredient over an extended period of time. It is an ideal dosage form for an active ingredient with a short elimination half-life. An active ingredient with a short elimination half-life would be released in small portions over an extended period of time and thus less frequent administration is necessary and this improve patient compliance. Other advantages of these formulations include: decreased side effects, constant drug levels in the blood, improvement in treatment efficiency and reduction in cost of administration. Controlled release beads are formulated in such a way that the active ingredient is embedded in a matrix of insoluble substance like chitosan; the dissolving drug then has to find its way through the pores of the matrix into the surrounding medium. The chitosan matrix swells to form a gel, the drug then has to first dissolve in the matrix and diffuse through the outer surface into the surrounding medium. Chitosan is a biocompatible, biodegradable polymer of natural origin. It has mucoadhesive properties as well as the ability to manipulate the tight junctions in the epithelium membrane and these properties have qualified chitosan as an effective drug carrier in controlled release dosage forms. The effect of a modern controlled release polymer namely Kollidon® SR in combination with chitosan on drug release was investigated. Ketoprofen was chosen as model drug. Ketoprofen is an anti-inflammatory drug that causes gastrointestinal side effects in conventional dosage forms. Ketoprofen has a short elimination half-life of 2.05 ± 0.58 h and this characteristic makes it an ideal candidate for use in a controlled release formulation. The aim of this study was to achieve controlled release and minimize gastrointestinal effects of ketoprofen with chitosan particles. Kollidon® SR was used as polymer because it exhibits pH independent release characteristics and previous studies have shown potential for this combination. Chitosan beads and chitosan-Kollidon® SR beads, as well as chitosan granules and chitosan-Kollidon® SR granules, were prepared and investigated as potential controlled release formulations. Chitosan beads were prepared through the inotropic gelation method using tripolyphosphate as a cross linking agent. Granules were prepared through wet granulation using 2% v/v acetic acid as the granulating fluid or by dissolving ketoprofen in ethanol and Kollidon® SR in 2-pyrrolidinone and using the solution as granulating fluid. Kollidon® SR was added in concentrations of 0.25, 0.5 and 1% (w/v) in the bead formulations and concentrations of 1, 5 and 10% (w/w) in the granule formulations. The beads and granules were characterised by evaluating the following properties: morphology, drug loading and drug release. Additionally swelling and friability tests were also conducted on the bead formulations. The cross linking times of the bead formulations were varied to investigate the effect of cross linking time on the characteristics of the beads. Chitosan-Kollidon® SR beads showed promising results for controlled release formulations and ketoprofen were released over an extended period of time. Drug loading of the plain chitosan beads was 74.65 ± 0.71% and it was noted that the inclusion of Kollidon® SR in the beads resulted in an increase in drug loading and the formulation containing 1% (w/v) Kollidon® SR, cross linked for 30 minutes had a drug loading of 77.38 ± 0.01%. Drug loading of the beads that were cross linked for a longer time were slightly lower which is an indication that some of the drug might have leached out during cross linking. The degree of swelling was promising with some beads swelling to a degree of 2.5 in phosphate buffer solution pH 5.6. Granules had a drug loading between 81.73 ± 1.53% and 93.30 ± 0.50%. Ketoprofen release from the beads and the granules in PBS pH 7.40 at 37 °C over a period of 6 hours were investigated. The bead formulations were more effective in achieving controlled release and it was noted that the bead formulations that was cross linked for a longer period was more efficient in achieving controlled release. The granules did not form a matrix and were not effective in achieving controlled release. Controlled release of ketoprofen were achieved and the results show potential for chitosan-Kollidon® SR formulations in the future. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2008.

A multidisciplinary literature survey revealed that copolymeric nanoparticles could be applied in various technologies such as the production of paint, adhesives, packaging material and lately especially drug delivery systems. The specialized application and investigation of copolymers in drug delivery resulted in the synthesis of two series of copolymeric materials, i.e. poly(styrene-co-methyl methacrylate) (P(St-co-MMA)) and poly(styrene-co-ethyl methacrylate) (P(St-co-EMA)) were synthesized via the technique of o/w microemulsion copolymerization. These copolymers have not as yet been utilized to their full potential in the development of new drug delivery systems. However the corresponding hydrophobic homopolymer poly(styrene) (PS) and the hydrophilic homopolymer poly(methyl methacrylate) (PMMA) are known to be biocompatible. Blending of homopolymers could result in novel applications, however is virtually impossible due to their unfavorable mixing entropies. The immiscibility challenge was overcome by the synthesis of copolymers that combined the properties of the immiscible homopolymers. The synthesized particles were analyzed by gel permeation chromatography combined with multi-angle laser light scattering (GPC-MALLS) and attenuated total reflectance Fourier infrared spectroscopy (ATR-FTIR). These characterizations revealed crucial information to better understand the synthesis process and particle properties i.e. molecular weight, nanoparticle size and chemical composition of the materials. Additionally, GPC-MALLS revealed the copolymer chain conformation. These characterizations ultimately guided the selection of appropriate copolymer nanoparticles to develop a controlled-release drug delivery system. The selected copolymers were dissolved in a pharmaceutically acceptable solvent, tetrahydrofuran (THF) together with a drug, rifampin. Solvent casting of this dispersion resulted in the evaporation of the solvent and assembly of numerous microscale copolymer capsules. The rifampin molecules were captured in these microcapsules through a process of phase separation and coacervation. These microcapsules finally sintered to produce a multi-layer film with an unusual honeycomb structure, bridging yet another size scale hierarchy. Characterization of these delivery systems revealed that both series of copolymer materials produced films capable of controlling drug release and that could also potentially prevent biofilm adhesion. / Thesis (Ph.D. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2008.

This study is undertaken to improve the performance of a Chemotherapy Treatment Unit by increasing the throughput of the clinic and reducing the average patients’ waiting time. In order to achieve this objective, a simulation model of this system is built and several scenarios that target matching the arrival pattern of the patients and resources availability are designed and evaluated. After performing detailed analysis, one scenario proves to provide the best system’s performance. The best scenario determines a rational arrival pattern of the patient matching with the nurses’ availability and can serve 22.5% more patients daily. Although the simulation study shows the way to serve more patients daily, it does not explain how to sequence them properly to minimize the average patients’ waiting time. Therefore, an efficient scheduling algorithm was developed to build a scheduling template that minimizes the total flow time of the system.

A multidisciplinary literature survey revealed that copolymeric nanoparticles could be applied in various technologies such as the production of paint, adhesives, packaging material and lately especially drug delivery systems. The specialized application and investigation of copolymers in drug delivery resulted in the synthesis of two series of copolymeric materials, i.e. poly(styrene-co-methyl methacrylate) (P(St-co-MMA)) and poly(styrene-co-ethyl methacrylate) (P(St-co-EMA)) were synthesized via the technique of o/w microemulsion copolymerization. These copolymers have not as yet been utilized to their full potential in the development of new drug delivery systems. However the corresponding hydrophobic homopolymer poly(styrene) (PS) and the hydrophilic homopolymer poly(methyl methacrylate) (PMMA) are known to be biocompatible. Blending of homopolymers could result in novel applications, however is virtually impossible due to their unfavorable mixing entropies. The immiscibility challenge was overcome by the synthesis of copolymers that combined the properties of the immiscible homopolymers. The synthesized particles were analyzed by gel permeation chromatography combined with multi-angle laser light scattering (GPC-MALLS) and attenuated total reflectance Fourier infrared spectroscopy (ATR-FTIR). These characterizations revealed crucial information to better understand the synthesis process and particle properties i.e. molecular weight, nanoparticle size and chemical composition of the materials. Additionally, GPC-MALLS revealed the copolymer chain conformation. These characterizations ultimately guided the selection of appropriate copolymer nanoparticles to develop a controlled-release drug delivery system. The selected copolymers were dissolved in a pharmaceutically acceptable solvent, tetrahydrofuran (THF) together with a drug, rifampin. Solvent casting of this dispersion resulted in the evaporation of the solvent and assembly of numerous microscale copolymer capsules. The rifampin molecules were captured in these microcapsules through a process of phase separation and coacervation. These microcapsules finally sintered to produce a multi-layer film with an unusual honeycomb structure, bridging yet another size scale hierarchy. Characterization of these delivery systems revealed that both series of copolymer materials produced films capable of controlling drug release and that could also potentially prevent biofilm adhesion. / Thesis (Ph.D. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2008.

Software development is increasingly conducted in a recurrent fashion, where the same product or service is continuously being developed for the marketplace. Still, we lack detailed studies about this particular context of software development. Against this backdrop, this dissertation presents an action research study into Software Inc., a large multi-national software provider. The research addressed the challenges the company faced in managing releases and organizing software process improvement (SPI) to help recurrently develop and deliver a specific product, Secure-on-Request, to its customers and the wider marketplace. The initial problem situation was characterized by recent acquisition of additional software, complexity of service delivery, new engineering and product management teams, and low software development process maturity. Asking how release management can be organized and improved in the context of recurrent development of software, we draw on Pettigrew’s contextualist inquiry to focus on the ongoing interaction between the contents, context and process to organize and improve release cycle practices and outcomes. As a result, the dissertation offers two contributions. Practically, it contributes to the resolution of the problem situation at Software Inc. Theoretically, it introduces a new software engineering discipline, release cycle management (RCM), focused on recurrent delivery of software, including SPI as an integral part, and grounded in the specific experiences at Software Inc.

Fierce competition in the market is driving software vendors to rely on Software-as-a-Service (SaaS) strategies and to continuously match new software versions with customers’ needs and competitors’ moves. Although release management as a recurrent activity related to SaaS arguably shapes how a vendor services its customers, the literature is surprisingly limited on how software releases are managed to support SaaS strategies. Against this backdrop, we present a collaborative action-research study with Software Inc., a large multi-national software provider, focused on improving the release cycle management process for a complex security software service. The study is part of a comprehensive intervention into Software Inc. that combines a perspective rooted in software process improvement and engineering practices with one rooted in service delivery and customer interactions. The part that is reported in this dissertation draws on the service-dominant logic framework to analyze how the release cycle management process was organized to improve Software Inc.’s ongoing value co-creation with its customers. As a result, the study contributed to improving release cycle management at Software Inc. and it expands industry knowledge about the challenges and opportunities for software vendors to manage releases and improve the value delivered to and co-created with their customers. This added knowledge is of interest to both practitioners and researchers as SaaS strategies increasingly shape the industry with important implications for how software is released.

Microgels are lightly cross-linked hydrogel particles in the sub-micrometer to micrometer size range with a capacity to drastically change their volume in response to changes in the external environment. Microgels have an ability to bind and store substances such as biomacromolecular drugs, notably proteins and peptides, and release them upon stimuli, making them potential candidates as drug delivery vehicles and functional biomaterials. This thesis aims at clarifying important factors affecting peptide-microgel interactions. These interactions were studied by micromanipulator-assisted light and fluorescence microscopy focusing on microgel deswelling in response to peptide binding, as well as re-swelling in response to peptide release or enzymatic degradation. To evaluate peptide uptake in microgels, solution depletion measurements were used whereas the peptide secondary structure was investigated by circular dichroism. In addition, the peptide and enzyme distribution within microgels was analyzed with confocal microscopy. Results presented in this thesis demonstrate that peptide incorporation into microgels, as well as peptide-induced microgel deswelling, increases with peptide length and charge density. In addition, results demonstrate that the peptide charge (length) rather than peptide charge density determines microgels deswelling. End-to-end cyclization is shown to not noticeably influence peptide-microgel interactions, suggesting that peptide cyclization can be used in combination with oppositely charged microgel carriers to improve the proteolytic and chemical stability of the peptide compared to the corresponding linear variant. Peptide secondary structure is found to drastically affect peptide incorporation into, and release from, oppositely charged microgels. Furthermore, it is shown that microgel charge density, peptide molecular weight, and enzyme concentration all greatly influence microgel bound peptide degradation. Of importance for applications, protective effects of microgels against proteolytic peptide degradation are observed only at sufficiently high microgel charge densities. Enzyme-mediated microgel degradation is shown to increase with increasing enzyme concentration, while an increased peptide loading in microgels causes a concentration-dependent decrease in microgel degradation. Taken together, results obtained in this work have provided some insight into factors of importance for rational use of microgels as delivery systems for protein or peptide drugs, but also in a host of other biomedical applications using weakly cross-linked polymer systems.

Darbo tikslas: įvertinti gamybinėse vaistinėse pagamintų tepalų su salicilo rūgštimi kokybę nustatant veikliosios medžiagos atpalaidavimą in vitro ir pasiūlyti alternatyvios sudėties ir gamybos technologijos puskietes sistemas, pasižyminčias ne mažesniu salicilo rūgšties atpalaidavimu in vitro. Darbo uždaviniai: 1. Parinkti ir pritaikyti salicilo rūgšties kiekybinės analizės metodiką; 2. Parinkti tinkamas sąlygas salicilo rūgšties atpalaidavimo iš tepalų tyrimams in vitro; 3. Ištirti salicilo rūgšties atpalaidavimą in vitro iš Lietuvos vaistinėse pagamintų tepalų; 4. Sumodeliuoti alternatyvios sudėties puskietes sistemas su salicilo rūgštimi, jas pagaminti ir įvertinti jų kokybę; 5. Ištirti salicilo rūgšties atpalaidavimą in vitro iš sumodeliuotų puskiečių sistemų bei palyginti gautus atpalaidavimo rezultatus su vaistinėse pagamintų tepalų atpalaidavimo rezultatais. Metodai: Salicilo rūgšties išsiskyrimas iš puskiečių sistemų tirtas naudojant modifikuotas Franz tipo celes. Salicilo rūgštis kiekybiškai nustatyta spektrofotometrijos metodu naudojant spektrofotometrą Agilent 8453, bangos ilgis 296 nm. Kalibracinio grafiko koncentracija ribose 0,005-0,03 mg/ml. Tepalų kokybė nustatyta vertinant tepalo pH ir dinaminę klampą. Rezultatai: po 4 h 5 % salicilo rūgšties tepalai atpalaidavo salicilo rūgšties: LSMU vaistinės- 3,36±0,16 %, “Ąžuolyno” vaistinės- 2,54±0,12 %, UAB “VJV“- 2,71±0,20 %, eksperimentinis 1,89±0,14 %, tepalai, pagaminti sudėtines medžiagas sumaišius grūstuvėje... [toliau žr. visą tekstą] / Objective of work: to evaluate quality of salicylic acid ointments manufactured by pharmacies by assessing release of salicylic acid in vitro and suggest alternative composition and technique semi- solid preparation, characterized by the same or better release of salicylic acid. Main tasks: 1. To select and adapt a suitable method for quantity analysis for salicylic acid; 2. To select appropriate conditions for salicylic acid release in vitro from semi- solid preparation; 3. To research release of salicylic acid in vitro from semi-solid preparations made by Lithuanian pharmacies; 4. To formulate semi- solid preparations containing salicylic acid and evaluate quality; 5. To research release of salicylic acid in vitro from formulated semi- solid preparations and compare release results with release results of semi- solid preparations made by Lithuanian pharmacies. Methods: release of salicylic acid from semi- solid preparations executed by using modificated vertical diffusion Franz cells. The quantity analysis executed by using spectrophotometric methods. UV- Vis spectrophotometer Agilent 8453, wavelength 296 nm, calibration curve within 0,005- 0,03 mg/ml. Ointments quality evaluated by pH and dynamic viscosity. Results: after 4 h 5 % salicylic acid ointments released salicylic acid: LSMU pharmacy‘s ointment- 3,36 %, “Ąžuolyno” pharmacy‘s ointment- 2,54 %, UAB “VJV“ ointment- 2,71 %, experimental ointment- 1,89 %; ointments made by mixing in mortar with glycerol- 2,27 %... [to full text]