The HIV-1 Gag p24 protein contains the HLA class-1 B*2705 restricted epitope KK10, responses to which are associated with delayed progression. Data from in vitro proteasomal digestion studies from our group has shown the production of a number of C-terminally extended and truncated epitopes containing KK10, produced in far higher quantities during proteasomal digestion than this “optimal epitope” and that the amount of antigen made in proteasomal digestion is instrumental in determining the development of immunodominance. This work aims to characterise the contribution of these naturally processed epitope forms to the cellular immune response to this region. Further proteasomal digestion studies have shown that the common KK10 intra-epitope escape mutant sequences R132K and L136M have major effects on epitope production by the proteasome and that a range of short peptides containing the N-terminal of the KK10 sequence are produced in large quantities by the proteasome. Recognition of the KK10 epitope forms by HLA B*2705 HIV-1 patients were characterised ex vivo and show recognition of KK10 epitope forms somewhat independent of the presence of KK10 recognition, we also show cross-recognition between KK10 epitope forms by CD8+ T cells, as well as recognition by CD4+ T-cells. TCR from CD8+ T-cells specific for KK10 epitope forms were found to share common features in the HLA binding CDR hyper-variable loops. Structural studies of the HLA B*2705 molecules in complex with the KK10 epitope forms show a shared binding motif at the N-terminus, and to a lesser extent, the C-terminus of the binding groove which may facilitate cross-recognition of complexes. In addition these studies show a potentially novel binding mode for a 14mer peptide, and refolding of truncated KK10 peptides as short as a 4mer with the HLA B*2705 molecule (crystallisation with a 6mer peptide shown). This demonstrates previously unrecognised flexibility of the HLA class-1 to bind and present peptides of different lengths to T-cells. We show that these HLA B*2705 binding-capable truncated peptides do not induce a CD8+ T-cell response in HLA B*2705 HIV-1 patients and may be able to block CD8+ T-cell responses to the KK10 epitope. This might represent a novel form of viral CTL escape. In addition we observe the presence of KK10 flanking mutations in patient sequences and significant associations between the presence of intra-epitope escape mutations, KK10 recognition and patterns of escape in flanking sequences. Finally we note the reduction in binding of KIR3DL1 to KK10 epitope forms relative to the KK10 epitope-HLA B*2705 complex. The presence of HLA B*2705 and KIR3DL1 associate with improved disease course in HIV-1 though the mechanism through which this occurs has yet to be defined.

Thesis advisor: Bernard O'Brien / This study investigated factors which influenced stable, primary love relationships among twelve lesbian couples who had been together at least fifteen years and had not reared children together. Each participant was interviewed separately in a retrospective, semi-structured interview that assessed the impact of selected factors over the course of the relationship. Each factor was examined to determine its influence in the beginning phase of the relationship (the first 5 years), in the middle phase (5-10 years into the relationship), and most recently (beyond 10 years into the relationship). Interpersonal dynamics as well as the influences of culture, religion, values, finances, and social supports were explored to determine their impact on relationship stability. / Thesis (PhD) — Boston College, 1994. / Submitted to: Boston College. School of Education. / Discipline: Counseling, Developmental Psychology, and Research Methods.

Faculty of Orthodontics School of Health Sciences 81/0315/8 Miltstein@global.co.za / The incidence of relapse following orthodontic treatment has always been of paramount interest to clinicians and research workers. Many investigations have been carried out at various Universities to assess the long-term stability of orthodontic treatment. This study assessed the stability of 31 cases at least ten years out of retention treated by post-graduate students in the Department of Orthodontics at the University of the Witwatersrand, Johannesburg. Associations between certain clinical parameters and postretention relapse were also evaluated. Occlusal changes which had taken place were assessed by evaluating data from models taken prior to treatment and comparing these with similar parameters at the end of treatment and, on average, just less than 13 years following the end of retention. Eleven parameters were recorded and measured according to a scoring system proposed by Sadowsky and Sakols. A total malocclusion score was obtained for each study model by calculating the algebraic sum of all the scores. The total malocclusion scores thus indicated the severity of malocclusion presented by each study model at each period. A further examination of each of the study models was carried out in order to establish the Irregularity Index. The anatomic points at which contact would be made were defined on each surface of the six mandibular anterior teeth. The distance between the contact points of the adjacent teeth were measured using a digital vernier caliper calibrated to the nearest 0,05mm. The sum of these 5 measurements provided the Irregularity Index. Values for mandibular irregularity were then grouped into minimal, moderate and severe categories. v Changes in the intercanine and intermolar widths were correlated with overbite, overjet and anterior mandibular crowding parameters. The study also determined whether the presence or absence of third molar teeth and/or premolar extraction therapy were associated with relapse. At postretention 54.8 percent of the sample displayed some degree of relapse in at least one of the variables studied. However, all of the variables studied showed a greater degree of stability than relapse. Canine relationship showed the most postretention stability, whilst deep bite, overjet and molar relationships showed the least. With a few exceptions, occlusal abnormalities which were considered to be severe at the commencement of treatment demonstrated a high degree of stability following corrective therapy, whereas the relapse of mild to moderate features prior to treatment was not as predictable. The small amount of change noted in intercanine and intermolar widths at all three stages of treatment were not significant predictors of relapse at the 5 percent significance level of the parameters assessed. Furthermore the presence or absence of third molar teeth was not a significant predictor of poor postretention malocclusion score, overjet or overbite. Similarly extraction therapy was not a significant predictor of lower incisor alignment relapse (p=1.0). The mean irregularity index of the whole sample following retention indicated that the lower incisors displayed minimal crowding (2.7 mm). Following at least ten years out of retention, treated cases in the Department of Orthodontics, University of the Witwatersrand, Johannesburg showed a high degree of stability for the parameters assessed.

<p>Benzodiazepines are drugs used to treat insomnia and anxiety. This group of drugs should be prescribed with the duty of care to the elderly because of it´s negative effects. Life expectancy is increasing because of the progress of drug development. Aging brings physical and psychological changes leading to changes in pharmacokinetic and pharmacodynamic features. Drug treatment is becoming increasingly widespread and contributes to the increasing number of interactions and complications for the elderly. The aim of the study was to illuminate the consequences of long-term use of benzodiazepines in the elderly. The study was conducted as a literature review based on 14 scientific articles that were analyzed. The result showed that the theme benzodiazepine use among the elderly could be divided into three categories; consequences out of long-term use, benzodiazepine users experiences and the nursing perspective. The category of impact out of long-term use of benzodiazepines revealed three sub-categories: physical consequences, psychological consequences and social consequences. Information and education to the elderly patients is important to make the elderly aware of the negative effects that may arise out of a long-term use of benzodiazepines. It is essential that nurses already in their basic education acquire more knowledge about benzodiazepine use among elderly in order to address these problems in the nursing care.</p>

Benzodiazepines are drugs used to treat insomnia and anxiety. This group of drugs should be prescribed with the duty of care to the elderly because of it´s negative effects. Life expectancy is increasing because of the progress of drug development. Aging brings physical and psychological changes leading to changes in pharmacokinetic and pharmacodynamic features. Drug treatment is becoming increasingly widespread and contributes to the increasing number of interactions and complications for the elderly. The aim of the study was to illuminate the consequences of long-term use of benzodiazepines in the elderly. The study was conducted as a literature review based on 14 scientific articles that were analyzed. The result showed that the theme benzodiazepine use among the elderly could be divided into three categories; consequences out of long-term use, benzodiazepine users experiences and the nursing perspective. The category of impact out of long-term use of benzodiazepines revealed three sub-categories: physical consequences, psychological consequences and social consequences. Information and education to the elderly patients is important to make the elderly aware of the negative effects that may arise out of a long-term use of benzodiazepines. It is essential that nurses already in their basic education acquire more knowledge about benzodiazepine use among elderly in order to address these problems in the nursing care.

Intensive management of short rotation hybrid poplar (HP) plantations on agriculture land has demonstrated good early yields and promise as an alternative crop for farmers selling fibre to the forest industry. However, multiple rotations of HP may impact the future productivity of plantations through nutrient removals. The objectives, therefore, of this study were to determine the nutrient stores and fluxes for two HP plantations with differing site quality, fertilizer applications and past land management practices and to construct a 20-year nutrient budget to examine impacts of harvesting short rotation HP on long-term productivity.<p>Heights and biomass were measured by harvesting above- and below-ground and separating biomass into tree components; measurement of atmospheric deposition, mineral weathering, litterfall, litter decomposition, and leaching for HP plantations on an Alfalfa (HPA) and Pasture (HPP) sites in 2004-05. The budget was developed by averaging fluxes over 2 years and scaling up to a 20-year rotation. <p>Unfertilized treatments in the HPA plantation showed greater tree growth than all other treatments. Fertilized and unfertilized treatments had greater biomass production and nutrient pools than treatments at the HPP plantation. The fertilizer treatments did not affect on biomass production and nutrient accumulation.<p>Nutrient additions to the HPA were greater than the HPP plantations for leaf litterfall and leaching. Nutrient resorption from senescing leaves was greater at the HPP plantation suggesting that nutrient pools were smaller and that trees responded by keeping nutrients in the biomass. Fertilization at both plantations increased nutrient flow for inputs and outputs in 2004-05. Water leachate and leaf litterfall showed increased nutrient contents in fertilized treatments at both plantations.<p>A high fertility plantation that used fertilizer and practiced whole-tree harvesting exported more nutrients (and fibre) than a plantation with marginal site quality practicing stem-only harvesting. Time to replenish nutrients from atmospheric deposition and mineral weathering would range from 6 to 50 years for Ca and N, respectively, suggesting that subsequent plantations would require fertilizers to replenish soil nutrient reserves.<p>While HP plantations in Saskatchewan can produce high yields, they require large nutrient inputs and are inefficient (sequester a large amount) in nutrient use. High site quality is important to obtain high yields but conservational techniques, such as stem-only harvesting, are important in maintaining site quality over the long-term.

Intensive management of short rotation hybrid poplar (HP) plantations on agriculture land has demonstrated good early yields and promise as an alternative crop for farmers selling fibre to the forest industry. However, multiple rotations of HP may impact the future productivity of plantations through nutrient removals. The objectives, therefore, of this study were to determine the nutrient stores and fluxes for two HP plantations with differing site quality, fertilizer applications and past land management practices and to construct a 20-year nutrient budget to examine impacts of harvesting short rotation HP on long-term productivity.<p>Heights and biomass were measured by harvesting above- and below-ground and separating biomass into tree components; measurement of atmospheric deposition, mineral weathering, litterfall, litter decomposition, and leaching for HP plantations on an Alfalfa (HPA) and Pasture (HPP) sites in 2004-05. The budget was developed by averaging fluxes over 2 years and scaling up to a 20-year rotation. <p>Unfertilized treatments in the HPA plantation showed greater tree growth than all other treatments. Fertilized and unfertilized treatments had greater biomass production and nutrient pools than treatments at the HPP plantation. The fertilizer treatments did not affect on biomass production and nutrient accumulation.<p>Nutrient additions to the HPA were greater than the HPP plantations for leaf litterfall and leaching. Nutrient resorption from senescing leaves was greater at the HPP plantation suggesting that nutrient pools were smaller and that trees responded by keeping nutrients in the biomass. Fertilization at both plantations increased nutrient flow for inputs and outputs in 2004-05. Water leachate and leaf litterfall showed increased nutrient contents in fertilized treatments at both plantations.<p>A high fertility plantation that used fertilizer and practiced whole-tree harvesting exported more nutrients (and fibre) than a plantation with marginal site quality practicing stem-only harvesting. Time to replenish nutrients from atmospheric deposition and mineral weathering would range from 6 to 50 years for Ca and N, respectively, suggesting that subsequent plantations would require fertilizers to replenish soil nutrient reserves.<p>While HP plantations in Saskatchewan can produce high yields, they require large nutrient inputs and are inefficient (sequester a large amount) in nutrient use. High site quality is important to obtain high yields but conservational techniques, such as stem-only harvesting, are important in maintaining site quality over the long-term.

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This study evaluated the influence of annual land applications of Class B biosolids on the soil microbial and chemical properties monitored over 20 year period. The study was initiated in 1986 at the University of Arizona Marana Agricultural Center, Tucson, Arizona. The final application of biosolids was in March 2005, followed by growth of cotton from April through November 2005. Surface soil samples (0-30 cm) were collected monthly from March 2005 through December 2005, and analyzed for soil microbial properties. Soil cores (0-150 cm) were also collected in December and analyzed for various soil chemical properties. The study showed that land application of Class B biosolids had no significant effect on the number of indigenous soil microbial numbers including bacteria, actinomycetes, and fungi (no bacterial or viral pathogens were present in soil samples collected in December) but enhanced microbial activity in the biosolid amended plots. Bacterial diversity was not impacted after 20 years of land application when evaluated through cloning and sequence analysis of bacterial 16S rRNA. Both soils had a broad phylogenetic diversity comprising more than five major phyla including: Proteobacteria, Acidobacteria, Actinobacteria, Bacteroidetes, and Firmicutes. Chemical analyses showed that land application of biosolids significantly increased soil pH but did not affect soil salinity and CaCO3 values as compared with the control plots. However, this lack of increase in salinity was likely due to the leaching of soluble salts through the soil profile since irrigation rates. Land application significantly increased soil macro-nutrients including C, N and P and caution should be taken with respect to phosphate loadings to prevent nutrient contamination of surface waters. The biosolid amended soil concentrations of available and total metals were low (compared to the typical background soil metal concentrations). Metal concentrations attenuated rapidly with increasing soil depth, and were generally similar to values found in control soils at a depth of 150cm. Increases in available metal concentrations were modest. It is important to note that there are differences between these studies with respect to different cropping systems, biosolids type, climate and soil type, as well as irrigation rates in the arid southwest.