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Immunosuppression and malignancy in end stage kidney diseaseWebster, Angela Claire January 2006 (has links)
PhD / Introduction Kidney transplantation confers both survival and quality of life advantages over dialysis for most people with end-stage kidney disease (ESKD). The mortality rate on dialysis is 10-15% per year, compared with 2-4% per year post-transplantation. Short-term graft survival is related to control of the acute rejection process, requiring on-going immunosuppression. Most current immunosuppressive algorithms include one of the calcineurin inhibitors (CNI: cyclosporin or tacrolimus), an anti-metabolite (azathioprine or mycophenolate) and corticosteroids, with or without antibody induction agents (Ab) given briefly peri-transplantation. Despite this approach, between 15-35% of recipients undergo treatment for an episode of acute rejection (AR) within one year of transplantation. Transplantation is not without risk, and relative mortality rates for kidney recipients after the first post-transplant year remain 4-6 times that of the general population. Longer-term transplant and recipient survival are related to control of chronic allograft nephropathy (rooted in the interplay of AR, non-immunological factors, and the chronic nephrotoxicity of CNI) and limitation of the complications of chronic ESKD and long-term immunosuppression: cardiovascular disease, cancer and infection, which are responsible for 22%, 39% and 21% of deaths respectively. This thesis is presented as published works on the theme of immunosuppression and cancer after kidney transplantation. The work presented in the first chapters of this thesis has striven to identify, evaluate, synthesise and distil the entirety of evidence available of new and established immunosuppressive drug agents through systematic review of randomised trial data, with particular emphasis on quantifying harms of treatment. The final chapters use inception cohort data from the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA), which is first validated then used to explore the risk of cancer in more detail than was possible from trial data alone. Interleukin 2 receptor antagonists Interleukin-2 receptor antagonists (IL2Ra, commercially available as basiliximab and daclizumab) are humanised or chimeric IgG monoclonal antibodies to the alpha subunit of the IL2 receptor present only on activated T lymphocytes, and the rationale for their use has been as induction agents peri-transplantation. Introduced in the mid-1990s, IL2Ra use has increased globally, and by 2003 38% of new kidney transplant recipients in the United States and 25% in Australasia received an IL2Ra. This study aimed to systematically identify and synthesise the evidence of effects of IL2Ra as an addition to standard therapy, or as an alternative to other induction agents. We identified 117 reports from 38 randomised trials involving 4893 participants. Where IL2Ra were compared with placebo (17 trials; 2786 patients), graft loss was not different at one (Relative Risk -RR 0.84; 0.64 to 1.10) or 3 years (RR 1.08; 0.71 to1.64). AR was reduced at 6 months (RR 0.66; 0.59 to 0.74) and at 1 year (RR 0.66; 0.59 to 0.74) but cytomegalovirus (CMV) disease (RR 0.82; CI 0.65 to 1.03) and malignancy (RR 0.67; 0.33 to1.36) were not different. Where IL2Ra were compared with other antibody therapy no significant differences in treatment effects were demonstrated, but IL2Ra had significantly fewer side effects. Given a 40% risk of rejection, 7 patients would need treatment with IL2Ra in addition to standard therapy, to prevent 1 patient having rejection, with no definite improvement in graft or patient survival. There was no apparent difference between basiliximab and daclizumab. Tacrolimus versus cyclosporin for primary immunosuppression There are pronounced global differences in CNI use; 63% of new kidney transplant recipients in the USA but only 22% in Australia receive tacrolimus as part of the initial immunosuppressive regimen. The side effects of CNI differ: tacrolimus is associated more with diabetes and neurotoxicity, but less with hypertension and dyslipidaemia than cyclosporin, with uncertainty about equivalence of nephrotoxicity or how these relate to patient and graft survival, or impact on patient compliance and quality of life. This study aimed to systematically review and synthesise the positive and negative effects of tacrolimus and cyclosporin as initial therapy for renal transplant recipients. We identified 123 reports from 30 randomised trials involving 4102 participants. At 6 months graft loss was reduced in tacrolimus-treated recipients (RR 0•56; 0•36 to 0•86), and this effect persisted for 3 years. The relative reduction in graft loss with tacrolimus diminished with higher levels of tacrolimus (P=0.04), but did not vary with cyclosporin formulation (P=0.97) or cyclosporin level (P=0.38). At 1 year, tacrolimus patients suffered less AR (RR 0•69; 0•60 to 0•79), and less steroid-resistant AR (RR 0•49; 0•37 to 0•64), but more insulin-requiring diabetes (RR 1•86; 1•11 to 3•09), tremor, headache, diarrhoea, dyspepsia and vomiting. The relative excess in diabetes increased with higher levels of tacrolimus (P=0.003). Cyclosporin-treated recipients experienced significantly more constipation and cosmetic side-effects. We demonstrated no differences in infection or malignancy. Treating 100 recipients with tacrolimus instead of cyclosporin for the 1st year post-transplantation avoids 12 suffering acute rejection and 2 losing their graft but causes an extra 5 to become insulin dependent diabetics, thus optimal drug choice may vary among patients. Target of rapamycin inhibitors for primary immunosuppression Target of rapamycin inhibitors (TOR-I) are among the newest immunosuppressive agents and have a novel mode of action but uncertain clinical role. Sirolimus is a macrocyclic lactone antibiotic and everolimus is a derivative of sirolimus. Both prevent DNA synthesis resulting in arrest of the cell cycle. Animal models suggested TOR-I would provide synergistic immunosuppression when combined with CNI, but early clinical studies demonstrated synergistic nephrotoxicity. Since then diverse trials have explored strategies that avoid this interaction and investigated other potential benefits. The aim of this study was to systematically identify and synthesise available evidence of sirolimus and everolimus when used in initial immunosuppressive regimens for kidney recipients. We identified 142 reports from 33 randomised trials involving 7114 participants, with TOR-I evaluated in four different primary immunosuppressive algorithms: as replacement for CNI, as replacement for antimetabolites, in combination with CNI at low and high dose, and with variable dose of CNI. When TOR-I replaced CNI (8 trials, 750 participants), there was no difference in AR (RR 1.03; 0.74 to 1.44), but creatinine was lower (WMD -18.31 umol/l; -30.96 to -5.67), and bone marrow more suppressed (leucopoenia RR 2.02; 1.12 to 3.66, thrombocytopenia RR 6.97; 2.97 to 16.36, anaemia RR 1.67; 1.27 to 2.20). When TOR-I replaced antimetabolites (11 trials, 3966 participants), AR and CMV were reduced (RR 0.84; 0.71 to 0.99 and RR 0.49; 0.37 to 0.65) but hypercholesterolaemia was increased (RR 1.65; 1.32 to 2.06). When low was compared to high-dose TOR-I, with equal CNI dose (10 trials, 3175 participants), AR was increased (RR 1.23; 1.06 to 1.43) but GFR higher (WMD 4.27 ml/min; 1.12 to 7.41). When low-dose TOR-I and standard-dose CNI were compared to higher-dose TOR-I and reduced CNI AR was reduced (RR 0.67; 0.52 to 0.88), but GFR also reduced (WMD -9.46 ml/min; -12.16 to -6.76). There was no significant difference in mortality, graft loss or malignancy risk demonstrated for TOR-I in any comparison. Generally surrogate endpoints for graft survival favoured TOR-I (lower risk of acute rejection and higher GFR) and surrogate endpoints for patient outcomes were worsened by TOR-I (bone marrow suppression, lipid disturbance). Long-term hard-endpoint data from methodologically robust randomised trials are still needed. Monoclonal and polyclonal antibody therapy for treating acute rejection Strategies for treating AR include pulsed steroids, an antibody (Ab) preparation, the alteration of background immunosuppression, or combinations of these options. In 2002, in the USA 61.4% of patients with AR received steroids, 20.4% received Ab and 18.2% received both. The Ab available for AR are not new: horse and rabbit derived polyclonal antibodies (ATG and ALG) have been used for 35 years, and a mouse monoclonal antibody (muromonab-CD3) became available in the late 1980s. These preparations remove the functional T-cell population from circulation, producing powerful saturation immunosuppression which is useful for AR but which may be complicated by immediate toxicity and higher rates of infection and malignancy. The aim of this study was to systematically evaluate and synthesise all evidence available to clinicians for treating AR in kidney recipients. We identified 49 reports from 21 randomised trials involving 1394 participants. Outcome measures were inconsistent and incompletely defined across trials. Fourteen trials (965 patients) compared therapies for 1st AR episodes (8 Ab versus steroid, 2 Ab versus another Ab, 4 other comparisons). In treating first rejection, Ab was better than steroid in reversing AR (RR 0.57; CI 0.38 to 0.87) and preventing graft loss (RR 0.74; CI 0.58 to 0.95) but there was no difference in preventing subsequent rejection (RR 0.67; CI 0.43 to 1.04) or death (RR 1.16; CI 0.57 to 2.33) at 1 year. Seven trials (422 patients) investigated Ab treatment of steroid-resistant rejection (4 Ab vs another Ab, 1 different doses Ab, 1 different formulation Ab, 2 other comparisons). There was no benefit of muromonab-CD3 over ATG or ALG in reversing rejection (RR 1.32; CI 0.33 to 5.28), preventing subsequent rejection (RR 0.99; CI 0.61 to 1.59), graft loss (RR 1.80; CI 0.29 to 11.23) or death (RR 0.39; CI 0.09 to 1.65). Given the clinical problem caused by AR, comparable data are sparse, and clinically important differences in outcomes between widely used interventions have not been excluded. Standardised reproducible outcome criteria are needed. Validity of cancer data in an end stage kidney disease registry Registries vary in whether the data they collect are given voluntarily or as a requirement of law, the completeness of population coverage, the breadth of data collected and whether data are assembled directly or indirectly through linkage to other databases. Data quality is crucial but difficult to measure objectively. Formal audit of ANZDATA cancer records has not previously taken place. The aim of this study was to assess agreement of records of incident cancer diagnoses held in ANZDATA (voluntary reporting system) with those reported under statute to the New South Wales (NSW) state Central Cancer Registry (CCR), to explore the strengths and weaknesses of both reporting systems, and to measure the impact of any disagreement on results of cancer analyses. From 1980-2001, 9453 residents received dialysis or transplantation in NSW. Records from ANZDATA registrants were linked to CCR using probabilistic matching and agreement between registries for patients with 1 or more cancers, all cancers and site-specific cancer was estimated using the kappa-statistic (κ). ANZDATA recorded 867 cancers in 779 (8.2%) registrants; CCR 867 cancers in 788 (8.3%), with κ =0.76. ANZDATA had sensitivity 77.3% (CI 74.2 to 80.2), specificity 98.1% (CI 97.7 to 98.3) if CCR records were regarded as the reference standard. Agreement was similar for diagnoses whilst receiving dialysis (κ =0.78) or after transplantation (κ =0.79), but varied by cancer type. Melanoma (κ =0.61) and myeloma (κ =0.47) were less good; lymphoma (κ =0.80), leukaemia (κ =0.86) and breast cancer (κ =0.85) were very good. Artefact accounted for 20.8% non-concordance but error and misclassification did occur in both registries. Cancer risk did not differ in any important way whether estimated using ANZDATA or CCR records. Quality of cancer records in ANZDATA are high, differences largely explicable, and seem unlikely to alter results of analyses. Risk of cancer after kidney transplantation Existing data on the magnitude of excess risk of cancer across different kidney recipient groups are sparse. Quantifying an individual transplant candidate’s cancer risk informs both pre-transplant counselling, treatment decisions and has implications for monitoring, screening and follow-up after transplantation. The aims of this study were firstly to establish the risk of cancer in the post-transplant population compared to that experienced by the general population, and secondly to quantify how excess risk varied within the transplanted population, seeking to establish meaningful absolute risk estimates for post-transplant cancer based on unalterable recipient characteristics known a priori at the time of transplantation. 15,183 residents of Australia and New Zealand had a transplant between 1963 and 2004, and were followed for a median of 7.2 years (130,186 person-years), with 1642 (10.8%) developing cancer. Overall, kidney recipients had 3 times the cancer risk, with risk inversely related to age (Standardised Incidence Ratio of 15 to 30 in children reducing to 2 in people > 65 years). Female recipients aged 25 -29 had rates of cancer (779.2/100,000) equivalent to women aged 55 - 59 from the general population. The risk pattern of lymphoma, colorectal and breast cancer was similar to the overall age trend, melanoma showed less variability across ages and prostate cancer showed no risk increase. Within the transplanted population cancer risk was affected by age differently for each sex (P=0.007), and was elevated for recipients with prior non-skin malignancy (Hazard Ratio: HR 1.40; 1.03 to 1.89), of white race (HR 1.36; 1.12 to 1.89), but reduced for those with diabetic ESKD (HR 0.67; 0.50 to 0.89) Rates of cancer in kidney recipients were similar to non-transplanted people 20 -30 years older, but risk differed across patient groups. Men aged 45 - 54 at transplantation with graft function at 10 years had a risk of cancer that varied from 1 in 13 (non-white, diabetic ESKD, no prior cancer) to 1 in 5 (white, prior cancer, ESKD from other causes).
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Strategic alliance as an entrepreneurial stimulus for learning in mature stage organizations : a case study of financial services organizations entering into cross industry agreement strategic alliancesRees, Alan Norman, n/a January 2005 (has links)
Sustained success for an organization is based upon its ability to constantly realign with opportunities that emerge within their markets. Thus, organizations must continually evolve as markets evolve.
This thesis examined how mature stage organizations within the financial services industry can adopt entrepreneurial approaches to learn, evolve and improve their competitiveness. Despite the rate of technological change, globalization, and convergence of industries that has occurred in the last decade, there is no clear model to support the adoption of entrepreneurial activities within mature stage organizations. Adopting an exploratory qualitative case study approach, the researcher interviewed informants with experience in the financial services industry in Australia, Europe, North and South Asia, and the United States of America to explore the research question: How do mature stage organizations integrate strategic alliances as an entrepreneurial approach and capitalize on learning in response to evolving markets?
Interviewing key informants within the financial services industry, the study confirmed a range of means of conceptualizing, introducing, and managing new business initiatives through strategic alliances. These findings were synthesized into a hypothetical organization in which, it became evident, the more entrepreneurial and innovative the organization became, the more capable it was of sourcing and responding to new opportunities within existing and related markets.
The study confirmed the need in strategic alliances for shared vision, strong leadership, effective communication of the organization's direction and strategy, a culture that embraces flexibility, business competence, a commitment to respect and manage differences between organizations, an ability to work collaboratively, and a willingness to upgrade or replace business processes and technologies to support innovation.
The study sought to provide an understanding of how entrepreneurial approaches can remain fluid rather than become static, and how they can be preserved within mature organizations. The importance of leadership, commonality of vision, collaboration, communication, integration of business structures and processes, and willingness to learn from each other began to emerge as central issues from the initial interviews. Consequently, a second research question was added: How do partnering organizations operating in the mature stage of a corporate life cycle within the construct of a cross industry agreement strategic alliance adopt an entrepreneurial approach and mutually learn to recast the direction of their relationship?
The study confirmed that organizations should develop and support a culture that embraces learning, flexibility and change. Entrepreneurial organizations require vision, leadership, business structures, processes, and competencies to support innovation.
This research adds to the field by establishing that innovation is embedded in the ability of partnering organizations to learn continuously and collaboratively. In doing so, they become more capable of realigning with changing markets and creating and capitalizing on new markets. The research concludes that less hierarchical organizational structures within partnering organizations support strategic alliances and promote the ability of organizations to learn how to cooperate, collaborate, and grow individually and mutually together.
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Expression of stage-specific Fasciola proteases and their evaluation in vaccination trialsJayaraj, Ramamoorthi, Jayaraj@menzies.edu.au January 2008 (has links)
The liver flukes Fasciola hepatica and F. gigantica cause infectious disease in ruminants and humans. The geographical range of these two parasite species (temperate and tropical respectively) ensures that infection can occur worldwide. Although anthelmintic treatment is effective against disease, emerging drug resistant strains leads to the development of a vaccine. However, despite several decades of research, there is no commercial vaccine available. The main challenge at present is to produce recombinant proteins in an immunologically active form using recombinant DNA technology. This is an essential step in Fasciola vaccine production. Cysteine proteases are probably the most important facilitators of virulence in flukes and are produced by all stages of the fluke life-cycle. Two classes of cysteine protease are found in the excretory and secretory material of liver flukes- these are cathepsin L and cathepsin B. As such, the major aims of this thesis were to investigate the expression and purification of Fasciola recombinant cysteine proteins, and characterisation by SDS-PAGE and immunoblotting using monoclonal and polyclonal antibodies. These studies demonstrate the production of functionally active cathepsin proteins in S. cerevisiae BJ3505 cells which will lead to vaccine candidate analysis. The second aim of this thesis was to determine the protective efficacy of stage specific target antigens against experimental infection. In addressing this issue, the protective efficacy of single and multivalent recombinant protein vaccinations of adult stage F. hepatica cathepsin L5, immature F. gigantica cathepsin L1g and juvenile F. hepatica cathepsin B were analysed in Sprague Dawley rats against F. hepatica infection. This study demonstrates that juvenile fluke target antigen-cathepsin B induces better immune protection than adult fluke antigen-cathepsin L5. Cocktails of juvenile and adult stage fluke recombinant proteins (cathepsin B and L5) elicited the highest protective immunity against experimental infection and this combination showed not only reduction in fluke recovery and size of flukes, but also marked diminution in the intensity of liver lesions in vaccinated rats. In order to assess the immunogenic property of an early infective stage fluke secreting cysteine protease as a vaccine candidate, DNA vaccination vectors encoding cathepsin B were analysed in BALB/c mice. In this study, the ability of four DNA vaccination strategies such as secretory, chemokine-activating, lymph node targeting vectors encoding cathepsin B were assessed by antibody titre, antibody avidity, western blotting and ELIPSOT assay. The results have further validated the immunoprophylactic potential of a cathepsin B vaccine against F. hepatica. In this study, we have expressed and attained high yields of F. gigantica cathepsin L1g from E. coli BL21, and compared this to a yeast-expressed system. This protease was over-expressed and formed insoluble inclusion bodies that were subsequently solubilised with urea or guanidine hydrochloride. In order to purify the urea-solubilised protein, step-wise urea gradient chromatography was used. For refolding of solubilised protein, a dilution and dialysis procedure was utilised. Proteolytic activity was confirmed by gelatin SDS-PAGE analysis. In conclusion, the determination of the immune potential of recombinant stage specific antigens allows the development of effective vaccines against Fasciola infection.
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Selective transport of attached particles across the froth phaseSeaman, David Richard Unknown Date (has links)
Over many years, researchers in the field of flotation have developed an in-depth understanding of processes occurring in the pulp phase of flotation machines. Until recently, however, the froth phase has received little attention. The froth phase serves to separate bubble-particle aggregates from suspended slurry in a flotation cell. The mechanism of recovery by entrainment, its relationship to water recovery and particle size dependency is well understood. Froth recovery, (the fraction of particles entering the concentrate launder that entered the froth phase attached to air bubbles), is not well understood. Up until now, there has been doubt over whether this property is dependent on particle size and hydrophobicity. Difficulties in measuring froth recovery had previously prevented researchers from gaining a deeper understanding of the transport of attached particles across the froth phase. A novel device was designed and tested to measure froth recovery by isolating bubble-particle aggregates in the pulp-phase of flotation machines through the determination of the bubble loading in the pulp phase (mass of particles attached per unit volume of air bubbles). This technique can be used with other measurements to investigate froth selectivity by directly comparing these captured particles to those found in the froth phase. Evidence was collected at Red Dog Mine, Alaska and Newmont Golden Grove Operations, Western Australia which showed that the froth phase selectively transported more hydrophobic and smaller sized particles across the froth than less hydrophobic and larger particles. Particles collected in the device were compared to those found in the concentrate stream on a size by mineral by liberation class. Froth recovery was also calculated on a size by mineral by liberation class for two valuable sulphide minerals in a continuous 3m³ flotation cell. These results show that the froth phase is responsible for the upgrading of attached particles across the froth phase as well as for the separation of bubble-particle aggregates from suspended slurry. The pulp phase is responsible for creating bubble-particle aggregates through the attachment of hdyrophobic mineral particles to air bubbles. Many complex factors affect the extent to which this occurs including the size and hdyrophobicity of the particles, the size and number of air bubbles produced by the flotation machine, the rate of collisions between particles and bubbles and the overall chemistry of the system. This measurement of bubble loading presents an opportunity to measure the impact of all these factors on the successful creation of bubble-particle aggregates. Based on a literature review suggesting that there was a high probability of particles being detached at the pulp-froth interface due to the aggregates change in momentum, a three phase description of a flotation cell was proposed. The three phases were: pulp, pulp-froth interface and upper froth zones. A second froth recovery measurement technique (changing froth depth) was used in combination with the bubble load technique to determine the recovery across each of the two froth zones. It was found that the pulp-froth interface appears to be responsible for the selectivity observed across the froth phase as a whole. These findings will enable more in-depth research into the sub-process of the froth phase as well as assisting flotation cell design through a better understanding of the roles of the pulp-froth interface and the upper froth region.
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DIGITAL GAIN ERROR CORRECTION TECHNIQUE FOR 8-BIT PIPELINE ADCjaveed, khalid January 2010 (has links)
<p>An analog-to-digital converter (ADC) is a link between the analog and digital domains and plays a vital role in modern mixed signal processing systems. There are several architectures, for example flash ADCs, pipeline ADCs, sigma delta ADCs,successive approximation (SAR) ADCs and time interleaved ADCs. Among the various architectures, the pipeline ADC offers a favorable trade-off between speed,power consumption, resolution, and design effort. The commonly used applications of pipeline ADCs include high quality video systems, radio base stations,Ethernet, cable modems and high performance digital communication systems.Unfortunately, static errors like comparators offset errors, capacitors mismatch errors and gain errors degrade the performance of the pipeline ADC. Hence, there is need for accuracy enhancement techniques. The conventional way to overcome these mentioned errors is to calibrate the pipeline ADC after fabrication, the so-called post fabrication calibration techniques. But environmental changes like temperature and device aging necessitates the recalibration after regular intervals of time, resulting in a loss of time and money. A lot of effort can be saved if the digital outputs of the pipeline ADC can be used for the estimation and correctionof these errors, further classified as foreground and background techniques. In this thesis work, an algorithm is proposed that can estimate 10% inter stage gain errors in pipeline ADC without any need for a special calibration signal. The efficiency of the proposed algorithm is investigated on an 8-bit pipeline ADC architecture.The first seven stages are implemented using the 1.5-bit/stage architecture whilethe last stage is a one-bit flash ADC. The ADC and error correction algorithms simulated in Matlab and the signal to noise and distortion ratio (SNDR) is calculated to evaluate its efficiency.</p>
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Känslor och tankar : En kvalitativ undersökning kring vad någramusikhögskolestudenter känner införoch vid framträdanden / Emotions and Thoughts : A qualitative study about what a few university music students feel before and during a performanceTobin, Jonas January 2009 (has links)
<p>Denna uppsats syftar till att få insikt i hur några högskolestuderande på klassisk gitarr och klassiskt piano som spelar solo upplever en konsertsituation. Huvudfrågorna har varit: Vad känner de? Har de några problem/svårigheter och i så fall hur beskriver de upplevelsen av detta? Detta har undersökts genom kvalitativa intervjuer med fem musikhögskolestudenter. Resultatet visar på att samtliga informanter upplever att de delvis påverkas negativt av nervositet i samband med en konsert. Nervositeten yttrar sig bland annat genom "fjärilar i magen", svettningar och negativa tankar innan konserten som handlar om att man inte är tillräckligt förberedd, att det kommer gå dåligt och att man skall spela fel. Under en konsert upplever de att de ibland har svårt att behålla koncentrationen och tankar på annat än musiken får fokus, t.ex. vilka som lyssnar, vad publiken tycker eller vad de skall äta till kvällsmat. Endast en av de fem intervjuade uttryckte att hon kände någon sorts glädje innan ett framträdande.</p> / <p>The purpose of this study is to investigate how university music students, playing classical guitar and classical piano, feel about a public performance. The main questions have been: What do they feel? Do they experience any difficulties and if so, how do they describe this? This has been examined by five interviews with music students at a university in Sweden.The results highlight that all of the informants feel that they are affected in a negative way by their nervousness. Signs of nervousness are butterflies in one's stomach, perspiration and negative thoughts prior to the actual concert situation. Those symptoms may deal with the idea of not being adequately prepared, a disastrous performance in general or simply playing wrong notes.During a performance they occasionally find it hard to stay concentrated, and thoughts about other things tend to get more focus: who is listening, what the audience will think or perhaps something as irrelevant as what the performer wants to eat for supper. Only one of the informants expressed that she felt a certain type of positive excitement about getting on stage before a concert.</p>
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The Complex Architecture of New Providence Island (Bahamas) Built by Multiple Pleistocene Sea Level HighstandsReid, Samuel B. 01 January 2010 (has links)
The present day Bahamian archipelago was deposited during sea level highstands when carbonate production was high enough to overfill accommodation space. This study unravels the complex stratigraphy and heterogeneity created by island accretion during and across the most recent Pleistocene highstands (MIS 5e, 9, and 11) using New Providence Island as a case study. Building upon the work of previous researchers, field based mapping was completed to understand the spatial relationships between ages, environments of deposition, and grainstone compositions across the island. Using the vertical and lateral relationships gained from detailed mapping, the depositional history of New Providence Island has been reconstructed for the Pleistocene MIS 5e, 9, and 11 sea level highstands. To map all of the environments of deposition, detailed criteria were created to recognize each environment observed on New Providence Island. Ages were estimated with field techniques and confirmed with dating done in previous studies and in this study, including both U-series techniques and amino acid racemization (AAR). Hand samples and short (< 1 m) cores were collected in the field and were used for petrographic analyses in the laboratory as well as whole rock AAR sampling for age determination. Detailed outcrop drawings were created, showing the lateral and vertical relationships of environments within outcrops. Meanwhile, maps and cross-sections were drafted to better understand island-wide relationships of environments, ages, and compositions. Based on age maps, New Providence formed by vertical and lateral accretion during the last three Pleistocene highstands (MIS 5e, 9, and 11), with a majority of deposition occurring during the most recent interglacial (MIS 5e, ~125 ka). Environment of deposition mapping revealed that island deposition occurred within shallow marine to eolian environments. Because of the abundance of MIS 5e deposits, the sedimentological complexity of an individual highstand (MIS 5e) reveals sub-orbital scale sea level changes. With mid-highstand sea level fluctuations apparent within the MIS 5e deposits on New Providence Island, a high level of lithofacies complexity could be expected within any individual sea level highstand. This study documents the complex vertical and lateral facies patterns associated with island building between and within sea level highstands.
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The effect of back stage information in services advertisements on consumers' services intangibility and perceived riskCheng, Kai-da 30 July 2007 (has links)
This study examines whether back stage information in services advertisements would significantly influence intangibility of services and consumers¡¦ perceived risk by experimental design, and whether ¡§back stage information-perceived risk¡¨ relation would mediated by intangibility. The researcher provides back stage information by print advertisements. The presentation of back stage information, the types of services, and the attributes of services are considered and included in research design to explore their roles in ¡§back stage information-intangibility-perceived risk¡¨ relation.
The result shows that intangibility of services and consumers¡¦ perceived risk are significantly lower after consumers reading advertisements with back stage information contrast with those without back stage information. Intangibility has partial mediating effect on ¡§back stage information-perceived risk¡¨ relation. Though, presenting back stage information simultaneously by picture and text has a slightly better effect than by text alone, however, the difference is not significant. The type and attribute of services have no moderation on ¡§back stage information-perceived risk¡¨ and ¡§intangibility-perceived risk¡¨ relations respectively.
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High Performance Class-AB Output Stage Operational Amplifiers for Continuous-time Sigma-delta ADCKrishnan, Lakshminarasimhan 2011 August 1900 (has links)
One of the most critical blocks in a wide-band continuous time sigma delta (CTSD) analog-to-digital converter (ADC) is the loop filter. For most loop filter topologies, the performance of the filter depends largely on the performance of the operational amplifiers (op-amps) used in the filter. The op-amps need to have high linearity, low noise and large gain over a wide bandwidth.
In this work, the impact of op-amp parameters like noise and linearity on system level performance of the CTSD ADC is studied, and the design specifications are derived for the op-amps. A new class-AB bias scheme, which is more robust to process variations and has an improved high frequency response over the conventional Monticelli bias scheme, is proposed. A biquadratic filter which forms the input stage of a 5th order low pass CTSD ADC is used as a test bench to characterize the op-amp performance. The proposed class-AB output stage is compared with the class-AB output stage with Monticelli bias scheme and a class-A output stage with bias current reuse. The filter using the new op-amp architecture has lower power consumption than the other two architectures. The proposed class AB bias scheme has better process variation and mismatch tolerance compared to the op-amp that uses conventional bias scheme.
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Känslor och tankar : En kvalitativ undersökning kring vad någramusikhögskolestudenter känner införoch vid framträdanden / Emotions and Thoughts : A qualitative study about what a few university music students feel before and during a performanceTobin, Jonas January 2009 (has links)
Denna uppsats syftar till att få insikt i hur några högskolestuderande på klassisk gitarr och klassiskt piano som spelar solo upplever en konsertsituation. Huvudfrågorna har varit: Vad känner de? Har de några problem/svårigheter och i så fall hur beskriver de upplevelsen av detta? Detta har undersökts genom kvalitativa intervjuer med fem musikhögskolestudenter. Resultatet visar på att samtliga informanter upplever att de delvis påverkas negativt av nervositet i samband med en konsert. Nervositeten yttrar sig bland annat genom "fjärilar i magen", svettningar och negativa tankar innan konserten som handlar om att man inte är tillräckligt förberedd, att det kommer gå dåligt och att man skall spela fel. Under en konsert upplever de att de ibland har svårt att behålla koncentrationen och tankar på annat än musiken får fokus, t.ex. vilka som lyssnar, vad publiken tycker eller vad de skall äta till kvällsmat. Endast en av de fem intervjuade uttryckte att hon kände någon sorts glädje innan ett framträdande. / The purpose of this study is to investigate how university music students, playing classical guitar and classical piano, feel about a public performance. The main questions have been: What do they feel? Do they experience any difficulties and if so, how do they describe this? This has been examined by five interviews with music students at a university in Sweden.The results highlight that all of the informants feel that they are affected in a negative way by their nervousness. Signs of nervousness are butterflies in one's stomach, perspiration and negative thoughts prior to the actual concert situation. Those symptoms may deal with the idea of not being adequately prepared, a disastrous performance in general or simply playing wrong notes.During a performance they occasionally find it hard to stay concentrated, and thoughts about other things tend to get more focus: who is listening, what the audience will think or perhaps something as irrelevant as what the performer wants to eat for supper. Only one of the informants expressed that she felt a certain type of positive excitement about getting on stage before a concert.
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