To see the other types of publications on this topic, follow the link: WFM system.
Dissertations / Theses on the topic 'WFM system'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'WFM system.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Obrtlík, Josef. "Návrh a implementace CRM systému pomocí low-code platformy ve firemním prostředí." Master's thesis, Vysoké učení technické v Brně. Fakulta podnikatelská, 2021. http://www.nusl.cz/ntk/nusl-444601.
Full textAbstract:
This master's thesis is focusing to create an operational CRM system in web interface of SystemBaker application in company environment – specifically for company named Mathesio s.r.o. In theoretical part there are explained concepts and technologies, which are needed to know to fully comprehend background of the developed application. Then there are introduced possible forms of developing this application, which serve for later assessment of economic benefits of this development form. In practical part there is de-scribed structure of database, use-cases and operational solution of this application and then economical assessment of benefits of this style of development.
2
Eminovic, Nejra, and Rana Tajik. "How to Improve a Planning System and Workflow in a Quality Control Laboratory : A Case Study at Fresenius Kabi in Sweden." Thesis, KTH, Industriell ekonomi och organisation (Inst.), 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-300149.
Full textAbstract:
Laboratories within quality control are very complicated to schedule due to the high product mix and diversified products tested with many different analysts and instruments. Thus, it requires a flexible planning system to change and improve the overall lab performance and increase efficiency. This thesis is a case study in collaboration with Fresenius Kabi AB and the quality control (QC) department in Uppsala. The QC department has an inflow of batches from the production department as well as from internal customers. Internal customers usually send batches that are part of stability studies or projects. These stability batches arrive at the QC department within irregular intervals and sometimes tightly adjacent, making the QC planning more complex, creating backlogs. Hence, the question in the study is formulated: ● How to improve a planning system and workflow in a quality control department? The current condition of batch inflow and how the planning system is managed today have to be understood to answer the question. Hence, the following sub-questions will be answered: ○ How is the current planning system at the quality control structured? ○ How is the inflow of stability batches at the department made more even andpredictable? This study aims to accomplish a practical planning system to prevent WIP, bottlenecks, and backlogs. The thesis is based on a qualitative method involving an inductive approach. The data collected mainly includes data from incoming batches, interviews, and literature studiesto gain multiple perspectives on the covered area. The study results showed that the internal customers were not satisfied with the current delivery times of QC. The common patterns identified are that internal customers want more contact and cooperation with the QC department. Furthermore, the result shows that the QC can handle the batches that arrive, but the planning system is not good enough. The proposed improvements to the current planning system are mainly to change it to a longer-term planning system and introduce a standard log or planning system between the internal departments. Also, QC should reorganize the lab and schedule based on common analysis to accomplish a higher efficiency of the scheduling. Further recommendations include more transparency and precise planning between departments to improve the inflow of the stability batches.Quality Control (QC) laboratorium är svåra att planera detta på grund den höga mängden och variationen av produkter. Det kräver således ett flexibelt planeringssystem för att förändra och förbättra prestandan och öka effektiviteten i laboratorier. Detta examensarbete är en fallstudie i samarbete med Fresenius Kabi AB och deras kvalitetsavdelningen i Uppsala. QC avdelningen har ett inflöde av batcher från produktionsavdelningen samt från de interna kunder. De interna kunderna skickar vanligtvis batcher som ingår i stabilitetsstudier eller projekt. Dessa stabilitets batchar inkommer till QC inom icke bestämda tidpunkter och ibland tätt inpå varandra, vilket försvårar planeringen inom QC vilket in sin tur skapar backloggar. Därav är frågeställningen i studien formulerad: ● Hur kan ett planeringssystem och arbetsflöde i ett kvalitetskontroll laboratoriumförbättras? För att kunna besvara denna frågeställning bör det aktuella planeringssystemet i avdelningen att undersökas. Därav kommer även dessa delfrågor att besvaras för att i denna studie: ● Hur är det nuvarande planeringssystemet strukturerat? ● Hur kan inflödet av stabilitets studier på avdelningen jämnas ut och bli mer förutsägbara? Syftet med denna studie är därav att effektivisera det nuvarande planeringssystem för att förhindra WIP, flaskhalsar och backlogs i QC avdelningen. Examensarbetet bygger på en kvalitativ metod med en induktiv forskningsansats. Den insamlade datan främst inkluderar data från inkommande batcher, intervjuer samt litteraturstudie för att få flera perspektiv av det undersökta ämnesområdet. Studiens resultat visade att samtliga interna kunder inte är nöjda med de nuvarande leveranstider som QC har. De gemensamma mönster som identifierats är att de interna kunderna önskar mer kontakt och samarbete med QC avdelningen. Vidare visar resultatet att QC bör ha kapaciteten som krävs för att kunna hanterade batcher som inkommer men att planeringen inte är tillräckligt bra. De förbättringsförslag som föreslås till det nuvarande planeringssystemet är främst att utveckla en mer långsiktig planering samt införa en gemensam logg. QC avdelningen på Fresenius Kabi bör även se över sin organisering och dela in grupper baserat på analyser och inte utrustning. Vidare rekommendationer inkluderar mer transparent och tydlig planering mellan avdelningarna.
3
Rothnie, Derek Malcolm. "Link optimisation for optical WDM transmission systems." Thesis, University College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298281.
Full text
4
Wongpaibool, Virach. "Effect of Dispersion on SS-WDM Systems." Thesis, Virginia Tech, 1998. http://hdl.handle.net/10919/36992.
Full textAbstract:
The purpose of this thesis is to investigate the effect of dispersion on a
spectrum-sliced WDM (SS-WDM) system, specifically a system employing a single-mode optical fiber. The system performance is expressed in term of the receiver sensitivity defined as the average number of photon per bit Np required for a given probability of bit error Pe. The receiver sensitivity is expressed in terms of two normalized parameters: the ratio of the optical bandwidth per channel and the bit rate m=B0/Rb=B0T, and the transmission distance normalized by the dispersion distance z/LD.
The former represents the effect of the excess beat noise caused by the signal fluctuation. The latter represents the effect of dispersion. The excess beat noise can be reduced by increasing the value of m (increasing the optical bandwidth B0 for a given bit rate Rb). However, a large m implies that the degradation due to the dispersion is severe in a system employing a single-mode fiber.
Therefore, there should be an optimum m resulting from the two effects. The theoretical results obtained from our analysis have confirmed this prediction. It is also shown that the optimum m (mopt) decreases with an increase in the normalized distance. This suggests that the dispersion strongly affects the system performance. The increase in the excess beat noise is traded for the decrease in the dispersion effect. Additionally, the maximum transmission distance is relatively short, compared to that in a laser-based system. This suggests that the SS-WDM systems with single-mode fibers are suitable for short-haul systems, such as high-speed local-access network where the operating bit rate is high but the transmission distance is relatively short.Master of Science
5
Buyuksahin, Oncel F. Feza. "Modulation Formats For Wavelength Division Multiplexing (wdm) Systems." Phd thesis, METU, 2009. http://etd.lib.metu.edu.tr/upload/12611039/index.pdf.
Full textAbstract:
Optical communication networks are becoming the backbone of both national and international telecommunication networks. With the progress of optical communication systems, and the constraints brought by WDM transmissions and increased bit rates, new ways to convert the binary data signal on the optical carrier have been proposed.
There are different factors that should be considered for the right choice of modulation format, such as information spectral density (ISD), power margin, and tolerance against group-velocity dispersion (GVD) and against fiber nonlinear effects like self-phase modulation (SPM), cross-phase modulation (XPM), four-wave mixing (FWM), and stimulated Raman scattering (SRS).
In this dissertation, the several very important modulation formats such as Non Return to Zero (NRZ), Return to Zero (RZ), Chirped Return to Zero (CRZ), Carrier Suppressed Return to Zero (CSRZ), Differential Phase Shift Keying (PSK) and Carrier Suppressed Return to Zero- Differential Phase Shift Keying (CSRZ-DPSK) will be detailed and compared.
In order to make performance analysis of such modulation formats, the simulation will be done by using VPItransmissionMakerTM WDM software.
6
Devaney, John F. L. "WDM of solitons in dispersion managed transmission systems." Thesis, Aston University, 1998. http://publications.aston.ac.uk/7977/.
Full textAbstract:
This thesis investigates the physical behaviour of solitons in wavelength division multiplexed (WDM) systems with dispersion management in a wide range of dispersion regimes. Background material is presented to show how solitons propagate in optical fibres, and key problems associated with real systems are outlined. Problems due to collision induced frequency shifts are calculated using numerical simulation, and these results compared with analytical techniques where possible. Different two-step dispersion regimes, as well as the special cases of uniform and exponentially profiled systems, are identified and investigated. In shallow profile, the constituent second-order dispersions in the system are always close to the average soliton value. It is shown that collision-induced frequency shifts in WDM soliton transmission systems are reduced with increasing dispersion management. New resonances in the collision dynamics are illustrated, due to the relative motion induced by the dispersion map. Consideration of third-order dispersion is shown to modify the effects of collision-induced timing jitter and third-order compensation investigated. In all cases pseudo-phase-matched four-wave mixing was found to be insignificant compared to collision induced frequency shift in causing deterioration of data. It is also demonstrated that all these effects are additive with that of Gordon-Haus jitter.
7
Cobbing, Benedict Louis. "The use of Landsat ETM imagery as a suitable data capture source for alien acacia species for the WFW programme." Thesis, Rhodes University, 2007. http://hdl.handle.net/10962/d1005532.
Full textAbstract:
Geographic Information System technology today allows for the rapid analysis of vast amounts of spatial and non-spatial data. The power of a GIS can only be effected with the rapid collection of accurate input data. This is particularly true in the case of the South African National Working for Water (WFW) Programme where large volumes of spatial data on alien vegetation infestations are captured throughout the country. Alien vegetation clearing contracts cannot be generated, for WFW, without this data, so that the accurate capture of such data is crucial to the success of the programme. Mapping Invasive Alien Plant (IAP) data within WFW is a perennial problem (Coetzee, pers com, 2002), because not enough mapping is being done to meet the annual requirements of the programme in the various provinces. This is re-iterated by Richardson, 2004, who states that there is a shortage of accurate data on IAP abundance in South Africa. Therefore there is a need to investigate alternate methods of data capture; such as remote sensing, whilst working within the existing WFW data capture standards. The aim of this research was to investigate the use of Landsat ETM imagery as a data capture source for mapping alien vegetation for the WFW Programme in terms of their approved mapping methods, for both automated and manual classification techniques. The automated and manual classification results were compared to control data captured by differential Global Positioning Systems (DGPS). The research tested the various methods of data capture using Landsat ETM images over a range of study sites of varying complexity: a simple grassland area, a medium complexity grassy fynbos site and a complicated indigenous forest site. An important component of the research was to develop a mapping (classification) Ranking System based upon variables identified by WFW as fundamental in data capture decision making: spatial and positional accuracy, time constraints and cost constraints for three typical alien invaded areas. The mapping Ranking System compared the results of the various mapping methods for each factor for the study sites against each other. This provided an indication of which mapping method is the most efficient or suitable for a particular area.
8
Li, Wei. "Modeling and simulation of wavelength-tunable laser diodes for WDM system." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0025/NQ51209.pdf.
Full text
9
Gerdin, Hulkko Johan. "Muspel and Surtr : CVD system and control program for WF6 chemistry." Licentiate thesis, Uppsala universitet, Oorganisk kemi, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-380973.
Full textAbstract:
CVD (Chemical Vapour Deposition) is an advanced technique for depositing a coating on a substrate. CVD implies that a solid phase is deposited on a normally heated substrate surface using a reactive, gaseous mixture. The reaction gas mixture must be carefully chosen to prevent homogeneous nucleation in the gas phase. As the solid phase is formed, gaseous by-products are formed and they must be removed from the CVD system. The thermally activated CVD process requires a deposition system which can regulate the total pressure and mass flows of the separate gas components as well as maintain a sufficiently high temperature to initiate a chemical reaction on the substrate surface. In this thesis a new CVD system was constructed to meet these challenges. Initially it will be used to deposit hard, wear resistant coatings but by changing the gases, it is possible to explore other chemical systems. The CVD system functions well up to a deposition temperature of 1100 ºC as long as the CVD processes are thermally activated. Apart from manual operation, a LabView control interface was implemented that can automate process steps by reading recipe files as csv (comma-separated variables). In this way complex coating architectures can be deposited. The aim of this thesis is to give a detailed description of the hardware set-up and of the software developed for it. Provided in this work are also a few examples of W and WN (tungsten nitride) coatings, including a multi-layered structure to show the potential of complex structures. Since the system also contains a titanium precursor, a TiN (titanium nitride) coating is presented to conceptually show the flexibility of the equipment.CVD är en avancerad teknik för att lägga en tunn film runt ett substrat. CVD innebär att en fast fas bildas på den normalt uppvärmda substratytan från en reaktiv gasblandning. Gasblandningen är väl vald att inte förorsaka homogen kärnbildning i gasfasen. När den fasta fasen bildas så bildas också gasformiga biprodukter som måste pumpas ut ur systemet. Den termiskt aktiverade CVD processen kräver ett system som kan styra total trycket och massflödet av de individuella gaskomponenterna samt hålla en tillräcklig temperatur för att initiera kemiska reaktioner på substratytan. I denna avhandling presenteras ett CVD-system byggt för att möta dessa utmaningar. Initialt kommer systemet att deponera hårda, slittåliga skikt men genom gasbyte byte av gas kan andra materialsystem utforskas. CVD-systemet kan deponera andra typer av filmer upp till en deponeringstemperatur på 1100°C så länge som CVD-processerna är termiskt aktiverade. Utöver manuell styrning har ett styrprogram i LabView implementerats för att medge automatisering av processtegen genom att läsa av receptfiler i csv-format. På det här sättet kan mer komplicerade skiktarkitekturer deponeras. Målet med detta arbete är att ge en detaljerad beskrivning av uppställningen samt mjukvaran som framställts. Ett antal exempel på W- (volfram) och WN-skikt (volframnitrid) presenteras tillsammans med en multiskiktslösning för att visa potentialen för komplicerade strukturer. Eftersom systemet även har tillgång till en titankälla presenteras ett TiN-skikt (titannitrid) för att konceptuellt demonstrera utrustningens flexibilitet.
10
Joshi, Ajay Jayant. "Wave-Pipelined Multiplexed (WPM) Routing for Gigascale Integration (GSI)." Diss., Georgia Institute of Technology, 2006. http://hdl.handle.net/1853/10549.
Full textAbstract:
The main objective of this research is to develop a pervasive wire sharing technique that can be easily applied across the entire range of on-chip interconnects in a very large scale integration (VLSI) system. A wave-pipelined multiplexed (WPM) routing technique that can be applied both intra-macrocell and inter-macrocell interconnects is proposed in this thesis. It is shown that an extensive application of the WPM routing technique can provide significant advantages in terms of area, power and performance. In order to study the WPM routing technique, a hierarchical approach is adopted. A circuit-level, system-level and physical-level analysis is completed to explore the limits and opportunities to apply WPM routing to current VLSI and future gigascale integration (GSI) systems. Design, verification and optimization of the WPM circuit and measurement of its tolerance to external noise constitute the circuit-level analysis. The physical-level study involves designing wire sharing-aware placement algorithms to maximize the advantages of WPM routing. A system-level simulator that designs the entire multilevel interconnect network is developed to perform the system-level analysis. The effect of WPM routing on a full-custom interconnect network and a semi-custom interconnect network is studied.
11
Li, Ji. "Design and analysis of survivable WDM mesh networks." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/hkuto/record/B38574846.
Full text
12
Galdino, Lídia 1982. "Analise de desempenho de redes opticas hibridas WDM/OCDM." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/258938.
Full textAbstract:
Orientadores: Edson Moschim, Luiz Henrique BonaniDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Eletrica e de Computação
Made available in DSpace on 2018-08-12T13:14:47Z (GMT). No. of bitstreams: 1 Galdino_Lidia_M.pdf: 1699308 bytes, checksum: 530cf633ab13e0be3952155525a69b24 (MD5) Previous issue date: 2008
Resumo: Neste trabalho investigamos o desempenho da tecnologia híbrida de multiplexação por divisão de comprimento de onda e multiplexação por divisão de códigos ópticos (WDM/OCDM) para rede óptica comutada por rajada e roteada por comprimento de onda (WR-OBS). Descrevemos uma arquitetura para o roteador de borda WDM/OCDM e derivamos expressões para a probabilidade de bloqueio da rajada no roteador de borda (BBP) a fim de analisar o desempenho da rede em função dos parâmetros de tempo de processamento no roteador de borda, da carga de tráfego da rede e do número de códigos ópticos. Nós estudamos o tempo de ocupação do canal, a largura de banda por caminho virtual e o fator de reutilização do caminho virtual e analisamos o desempenho da rede em função do tempo de atraso no roteador de borda, da proporção da taxa de bits e do diâmetro da rede caracterizado pelo tempo de reserva do canal. Analisamos topologias em malha considerando os parâmetros como a utilização efetiva do enlace, a probabilidade de bloqueio da rajada (BBP) e o número de códigos ópticos por enlace. As análises mostraram as muitas vantagens de aplicar a tecnologia WDM/OCDM quando comparada a tecnologia WDM puro, bem como esperado nível de Qualidade de Serviço (QoS).
Abstract: In this work we have investigated the performance of hybrid technology using wavelength and optical code division multiplexing (WDM/OCDM) for optical burst switching with acknowledgment (WR-OBS). We describe the architecture of WDM/OCDM edge router and derive expressions for the edge router burst blocking probability (BBP) in order to analyze the network behavior as function of parameters controlling the burst assembly delay, network traffic load and number of optical codes. We have studied the channel holding time, bandwidth per channel, virtual path factor re-use and analyze the network behavior as function of edge delay, bit-rate ratio and the diameter network characterized by the round-trip time. We have used mesh topology considering parameters such as effective link utilization, burst blocking probability (BBP) and the number of codes per link. Analysis shows the main advantages of applied WDM/OCDM technology when compared to pure WDM, as well as expected level of Quality of Service (QoS).
Mestrado
Telecomunicações
Mestre em Engenharia Elétrica
13
Huang, Yun-Yao. "A simple analytical model for asynchronous dense WDM/OOK systems." Thesis, Monterey, Calif. : Springfield, Va. : Naval Postgraduate School ; Available from National Technical Information Service, 1994. http://handle.dtic.mil/100.2/ADA283725.
Full text
14
Eisele, Andreas. "PHASE AND AMPLITUDE MODULATED OFDM FOR DISPERSION MANAGED WDM SYSTEMS." Master's thesis, University of Central Florida, 2008. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/4178.
Full textAbstract:
Amplitude and phase modulated optical OFDM (Orthogonal Frequency Division Multiplexing) are analyzed in a 50GBit/s single channel and 40GBit/s 5 channel 512 subcarrier non-ideal dispersion-compensated fiber optic communication systems. PM-OFDM is investigated as an alternative to AM-OFDM to alleviate the problem associated with amplitude-modulated signals in a nonlinear medium. The inherent dispersion compensation capability in OFDM (using a cyclic prefix) allows transmission over a link whose dispersion map is not exactly known. OFDM also mitigates the effects of dispersion slope in wavelength-division multiplexed (WDM) systems. Moreover, the overall dispersion throughout the transmission link may vary due to environmental effects and aging. OFDM is inherently tolerant to over- or under-compensation and dispersion slope mismatch. OFDM transmission over dispersive, non-dispersion managed fiber links using OFDM requires an overhead in excess of the maximum accumulated dispersion. Existing WDM systems usually employ periodic dispersion management. OFDM in these systems requires a smaller overhead. It is, however, more susceptible to nonlinearity due to the coherent beating of subcarriers after each dispersion-compensated span. The large variation in intensity associated with amplitude-modulated OFDM makes this modulation format more susceptible to nonlinear effects in fiber compared to phase-modulated signals. This holds true unless dispersion and EDFA noise lead to amplitude variations strong enough for PM-OFDM to be degraded by nonlinear effects as well. In conclusion OFDM is beneficial for non-ideal dispersion managed systems. PM-OFDM can further improve the performance.M.S.
Optics and Photonics
Optics and Photonics
Optics MS
15
Teotia, Seemant. "Saddlepoint Approximation for Calculating Performance of Spectrum-Sliced WDM Systems." Thesis, Virginia Tech, 1999. http://hdl.handle.net/10919/34329.
Full textAbstract:
Spectrum slicing is a novel technique for the implementation of wavelength-division multiplexing (WDM). While conventional WDM systems employ laser diodes operating at discrete wavelengths as carriers for the different data channels that are to be multiplexed, spectrum-sliced systems make use of spectral slices of a broadband noise source for the different data channels, thus being economically attractive.
In spectrum-sliced WDM systems with an optical preamplifier receiver there is an optimum m=BoT (Bo = optical channel bandwidth, T = bit duration) to minimize the average number of photons-per-bit (Np) required at the receiver for a given error probability (Pe). Both the optimum m and the minimum increase as interchannel interference increases. This has been analyzed previously by using the Gaussian approximation, or by assuming that the signals at the decision point are chi-square distributed. Although the chi-square distribution is valid in the case where there is no interference, it is not valid in the presence of interference, since the interference from the neighboring channel has a smaller bandwidth than the signal. In this thesis, a different method is used to analyze this problem. This method is called the Saddlepoint Approximation, and while the exact analysis required determination of the probability density function (pdf) of the received signal, the saddlepoint method makes use of moment generating functions (MGFs) which have a much simpler form and don't require the convolution operations the pdfs require.
The saddlepoint method is validated by comparing results obtained with the chi-square analysis for the no interchannel interference case when a rectangular shaped filter is used. The effect of non-rectangular spectra on receiver sensitivity with the use of the Saddlepoint Approximation is also investigated. After verifying its validity, the method is applied to the interchannel interference case caused by filter overlap. It is shown that for small filter overlap, use of an equivalent chi-square distribution is valid, but when the overlap becomes larger, the performance approaches that calculated using the Gaussian distribution. It is shown that there is an optimum filter overlap to maximize the total system throughput when total bandwidth is constrained. Operating at this optimum, the total system throughput is 135 Gbits/s when the total system bandwidth is 4.4 THz (35 nm) for a Bit Error Rate (BER) of 10e-9.
Master of Science
16
Nahas, Mousaab. "Investigation of different techniques to upgrade legacy WDM communication systems." Thesis, Aston University, 2006. http://publications.aston.ac.uk/15361/.
Full textAbstract:
This thesis presents experimental investigation of different effects/techniques that can be used to upgrade legacy WDM communication systems. The main issue in upgrading legacy systems is that the fundamental setup, including components settings such as EDFA gains, does not need to be altered thus the improvement must be carried out at the network terminal. A general introduction to optical fibre communications is given at the beginning, including optical communication components and system impairments. Experimental techniques for performing laboratory optical transmission experiments are presented before the experimental work of this thesis. These techniques include optical transmitter and receiver designs as well as the design and operation of the recirculating loop. The main experimental work includes three different studies. The first study involves a development of line monitoring equipment that can be reliably used to monitor the performance of optically amplified long-haul undersea systems. This equipment can provide instant finding of the fault locations along the legacy communication link which in tum enables rapid repair execution to be performed hence upgrading the legacy system. The second study investigates the effect of changing the number of transmitted 1s and Os on the performance of WDM system. This effect can, in reality, be seen in some coding systems, e.g. forward-error correction (FEC) technique, where the proportion of the 1s and Os are changed at the transmitter by adding extra bits to the original bit sequence. The final study presents transmission results after all-optical format conversion from NRZ to CSRZ and from RZ to CSRZ using semiconductor optical amplifier in nonlinear optical loop mirror (SOA-NOLM). This study is mainly based on the fact that the use of all-optical processing, including format conversion, has become attractive for the future data networks that are proposed to be all-optical. The feasibility of the SOA-NOLM device for converting single and WDM signals is described. The optical conversion bandwidth and its limitations for WDM conversion are also investigated. All studies of this thesis employ 10Gbit/s single or WDM signals being transmitted over dispersion managed fibre span in the recirculating loop. The fibre span is composed of single-mode fibres (SMF) whose losses and dispersion are compensated using erbium-doped fibre amplifiers (EDFAs) and dispersion compensating fibres (DCFs), respectively. Different configurations of the fibre span are presented in different parts.
17
Feng, Yumang. "Analysis of nonlinear effects on WDM system performance and a novel WDM channel monitoring method through HOS-based blind signal separation." Thesis, University of Liverpool, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406634.
Full text
18
Li, Ji, and 李季. "Design and analysis of survivable WDM mesh networks." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B38574846.
Full text
19
Huang, Hong. "Hybrid and resilient WDM mesh optical networks." Diss., Georgia Institute of Technology, 2002. http://hdl.handle.net/1853/15751.
Full text
20
Grah, Adrian. "Active and passive coupling in WDM photonic ring and bus networks." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ30088.pdf.
Full text
21
Kim, Christina Sujin, and Javed Singha. "WFP supply chain capacity in Ethiopia : an analysis of its sufficiency, constraints & impact." Thesis, Massachusetts Institute of Technology, 2010. http://hdl.handle.net/1721.1/61178.
Full textAbstract:
Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2010.Cataloged from PDF version of thesis.
Includes bibliographical references (p. 66-67).
The WFP's transport of food aid to Ethiopia's landlocked population is constrained by supply chain bottlenecks at the port, and limited availability of trucks for inland transport. How can the WFP supply chain be optimized to effectively operate within the given constraints? First, we assess Ethiopia's current food transport capacity - a critical factor for the WFP's ability to deliver humanitarian food aid. Specifically, we review the current and forecasted movement of goods, gather and analyze information on transport capacity versus demand, and address the impact of government policies and regulations on the road transport sector. As a result, our research helps the WFP in analyzing quantitative and qualitative factors used in selecting routes and mitigating port bottleneck issues. The results of our study may be used by the WFP and other humanitarian organizations which aid distressed populations.
by Christina Sujin Kim and Javed Singha.
M.Eng.in Logistics
22
Naeem, Usra. "Estimating dead space ventilation : a computational modelling approach towards evaluation of clinical estimates of dead space fraction in critically ill patients." Thesis, University of Nottingham, 2018. http://eprints.nottingham.ac.uk/51774/.
Full textAbstract:
Dead space is the part of tidal volume that does not participate in gas exchange and represents wasted ventilation. It is often increased in pulmonary diseases. Quantification of dead space by the original Bohr’s equation requires measuring mean alveolar pressure of CO2 (PACO2) and mixed expired partial pressure of CO2 (PĒCO2). Because of the difficulties and technical issues related with measuring PACO2 and PĒCO2, alternative methods have been proposed for the estimation of dead space. This thesis attempts to explore the performance of some methods proposed for the estimation of dead space to tidal volume ratio (VD/VT) in different pulmonary configurations and clinical scenarios. In the first study, we compared the performance of 5 different methods for the estimation VD/VT with the gold standard method in multiple ventilation/perfusion (V/Q) relationships. Six pulmonary configurations all with same alveolar dead space fraction of 0.25, but with different specific pattern of V/Q distribution were created within the Nottingham Physiology Simulator (NPS). Next, variations in the methods of estimating VD/VT upon varying 4 physiological factors were analysed. We concluded that the estimation of alveolar dead space ratio by 5 methods of estimating VD/VT is influenced by pattern of V/Q distribution and alterations in the relevant physiological factors. In the second study, we further analysed performance of 5 methods for estimating dead space ratio in patients with acute respiratory distress syndrome (ARDS). Nineteen ARDS subjects were created within the NPS and alveolar dead space fraction was measured by the gold standard method. Then, dead space fraction was determined by 5 different methods for estimating dead space fraction. We found that the estimates of dead space fraction measure different than the conventional equation in ARDS. In the third study, we compared efficacy of three lung recruitment maneuvers (RMs) in patients with ARDS. Six virtual ARDS patients were created and changes in dead space fraction, (Pa-E’CO2)/PaCO2 and other parameters were observed following the RMs. The results of this study showed that changes in (Pa-E’CO2)/PaCO2 closely relate with changes in VD/VT. These findings suggest that in clinical settings where it is not possible to measure dead space fraction, a simple estimate of VD/VT may be used to monitor the efficacy of RMs and titration of positive end-expiratory pressure. Simplified approaches for the estimation of dead space fraction may allow widespread use of this important physiological variable for diagnostic and prognostic purposes in critical care settings.
23
Martin, Matthew J. "Investigating the symptoms of airways disease." Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/46745/.
Full textAbstract:
Background Airways diseases are increasingly recognised to be poorly defined phenomena with overlapping pathophysiology and symptoms. They are a significant and growing cause of morbidity, with increasing numbers of people affected globally and no improvement in key outcomes in the UK for the last decade despite ever increasing expenditure. The classification of airway diseases has changed little in the last 50 years, and may no longer be fit for purpose due to the growing appreciation of the complexity and heterogeneity of airways disease and the advent of molecular-based diagnostic techniques to target specific treatment. Aim To investigate whether strategies based on the measurement of selected phenotypic and biological characteristics of airways disease can help to improve the understanding of their pathogenesis and targeting of treatment. Methods Three characteristics of airways disease, namely (1) exhaled nitric oxide, (2) chronic productive cough of unknown cause and (3) the airway microbiota were described/measured in selected cohorts of patients in three clinical studies. Measurement of each of these characteristics was used to answer focused clinical questions regarding the pathogenesis and treatment of aspects of airways disease. Results (1) The baseline measurement of FENO in steroid naïve subjects with symptoms suggestive of asthma had a low diagnostic value for asthma but was an excellent predictor of inhaled steroid treatment response. (2) A cohort of subjects with chronic productive cough of unknown cause was described. These subjects tended to have radiological evidence of airway dilatation and chronic inflammatory changes but not significant bronchiectasis. Their cough responded well to treatment with azithromycin, with ongoing neutrophilic airway inflammation a particularly strong predictor of treatment response. (3) There were no significant differences in the abundance or community structure of the bacterial communities in the airways between subjects with mild (BTS 2) or severe (BTS 4) asthma or between severe (BTS 4) asthma patients taking inhaled fluticasone or budesonide. However a number of differences in relative abundance of certain species (including enrichment of Haemophilus parainfluenzae in the fluticasone group) were noted on comparison of the groups. Conclusions This thesis provides support for a new approach to the classification and treatment of airways disease. The recognition of pathologically important processes (treatable traits) which can be used to predict response to targeted treatment has the potential to revolutionise the management of airways disease and result in improved patient outcomes.
24
Bhaker, Sangita. "Novel insight into uPAR function in the bronchial epithelium in asthma using functional genomics." Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/45133/.
Full textAbstract:
The urokinase plasminogen activator receptor (uPAR, PLAUR) is a cell surface receptor actively involved in the regulation of cell homeostasis. Expression is elevated in the bronchial epithelium in vivo and also in serum and sputum in asthma and elevated expression often indicates poor prognosis in a number of human diseases. The relative contribution of uPAR to asthma disease mechanisms is not fully understood and the functional roles of uPAR isoforms remains to be resolved. The key aims of this thesis were to i) investigate how the uPAR pathway may influence bronchial epithelial barrier properties; ii) investigate the gene expression patterns in the bronchial epithelium in asthma; iii) identify functions of different forms of uPAR in human bronchial epithelial cells (HBEC) and to iv) investigate the association between genetic polymorphisms spanning the PLAUR gene with clinical features and the presentation of asthma in moderate to severe asthma. Using two cell based approaches we identified an inverse relationship between soluble-cleaved uPAR expression and epithelial barrier properties. Importantly, we demonstrated that blocking uPAR-integrin interactions provides a potential therapeutic opportunity to improve epithelial barrier function. Using whole transcriptome analysis genes differentially expressed between cultured asthma and control subjects were identified which were related to cell growth, repair and immune regulation. Furthermore, uPAR expression was elevated in epithelial cells in asthma subjects compared to healthy controls, suggesting expression is inherently altered in the bronchial epithelium in asthma. Transcriptomics was used to provide novel insight into the specific and overlapping functions of uPAR isoforms and to determine the effects of elevated uPAR expression on HBEC function. Finally, the contribution of PLAUR genetic variants to clinical and immunological traits within asthma were investigated and found that PLAUR single nucleotide polymorphisms (SNPs) did not show an association with the traits measured in a severe asthma population. Overall this work has provided new insight into the function of uPAR as a regulator of the bronchial epithelium in asthma.
25
Bedford, Laura Elizabeth. "The emotional impact of screening for lung cancer." Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/47077/.
Full textAbstract:
Lung cancer is the most commonly diagnosed cancer and the most common cause of cancer related death worldwide. Population-based lung cancer screening programmes have been initiated in the USA and could soon be implemented in other countries. The overarching purpose of this thesis was to explore the emotional impact of lung cancer screening. The research was conducted as part of a clinical trial that was investigating the effectiveness of a blood autoantibody test, EarlyCDT®-Lung, in identifying individuals at the risk of lung cancer. A systematic review was conducted that aimed to identify factors associated with the emotional impact of screening for lung cancer. Participants with indeterminate test results, current smokers and females were more likely to experience negative non-specific and specific emotional outcomes. In addition to highlighting several key factors associated with higher levels of emotional distress following screening, factors that warranted further research were also identified. Such factors included age, education level, marital status, ethnic origin, and perceived risk of developing lung cancer. Finally, important methodological and theoretical limitations in the literature were identified. One key methodological limitation was that no studies measured positive emotional outcomes. A longitudinal study was conducted exploring the impact of lung cancer screening on positive affect, negative affect, lung cancer worry and distress specific to screening for lung cancer. Participants from each of the EarlyCDT®-positive, EarlyCDT®-negative, and control groups completed questionnaires containing emotional outcome measures at pre-randomisation and then at one, three, six and 12 months post randomisation. Scores for each outcome measure were described by groups over time and multilevel regression modelling was used to compare scores over time within and between groups. Results were reassuring as screening was found to have no clinically important impact on positive affect, negative affect, frequency of lung cancer worry or impact of lung cancer worry on mood and ability to perform daily activities. Although screening specific distress in the EarlyCDT®-positive group was significantly higher than that of the EarlyCDT®-negative group, it did reduce over time. Statistically significant and clinically important increases in the proportion of participants reporting anxiety about the results of future tests/treatments were identified. As a result of this finding, a further study was carried out to identify factors that could influence an individual’s level of anxiety about the results of future tests/treatment. Participants more at risk of reporting anxiety about the results of future tests/treatment were younger participants, non-white participants, current smokers and participants who did not own or have a mortgage on their home. Psychological variables associated with increased anxiety were: higher general anxiety scores, higher depression scores, higher negative affect scores, participants who reported that they were upset when they thought about their risk of lung cancer, participants who were worried about getting lung cancer, and those who reported the highest impact of lung cancer worry on mood and ability to perform daily activities. The final chapter of this thesis presents the results of a randomised controlled trial embedded within the emotional outcomes study (described above), which evaluated the effect of timing of monetary incentives (£5 voucher sent with questionnaire vs. £5 voucher sent on receipt of questionnaire) on the following outcomes: study participation rates, questionnaire response rates over time, the number of reminders sent and the completeness of returned questionnaires over time. Previous research had found that monetary incentives were useful in increasing response rates in clinical trials. Results from this trial extended the evidence base by showing that the timing of monetary incentives makes no difference to the above outcomes. In each chapter the findings of this thesis are discussed in terms of their contribution to knowledge. Recommendations for future research and clinical practice are also made within each chapter.
26
Naveed, Shams-un-nisa. "Matrix metalloproteinase-1 mediated extra-cellular matrix remodelling contributes to airway smooth muscle growth and asthma severity." Thesis, University of Nottingham, 2018. http://eprints.nottingham.ac.uk/50577/.
Full textAbstract:
Introduction Airway remodelling describes the histopathological changes in tissue architecture observed in obstructive lung diseases such as asthma and may have a negative impact on lung function. These changes do not appear to be treated by current asthma treatments. Changes observed during airway remodelling include increased thickness of airway smooth muscle (ASM) layer and enhanced extracellular matrix (ECM) deposition. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes, which facilitate tissue remodelling via ECM protein degradation. Matrix metalloproteinase-1 (MMP-1) and mast cells are present in the airways of patients with asthma (but not in healthy people). MMPs expression is highly regulated in lungs and is increased in disease states. My project aimed to assess MMP-1, -2 and -9 expression and activity in asthma airways. Furthermore, the underlying mechanism of MMP-1 activation and subsequently its role in airway remodelling and worsening asthma severity was investigated in the context of asthma exacerbation, which is thought to be an exaggerated lower airway inflammatory response to an environmental exposure such as respiratory virus infection. Methods Patients with stable asthma and healthy controls underwent spirometry, methacholine airway (PC20 ) challenge, exhaled nitric oxide (FeNO) test, bronchoscopy/bronchial washings and primary airway smooth muscle (ASM) cell cultures. A second asthma group (mild to moderate severity) and controls had symptom scores, spirometry and bronchoalveolar lavage (BAL) before and after rhinovirus inoculation. ECM was prepared from decellularised primary ASM cultures. MMP-1 protein levels and activity were assessed in bronchial fluid samples by enzyme-linked immunosorbent assay (ELISA), western blotting and fluorescent activity assay. ASM cell growth was measured by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) reduction assay and cell counts. Bronchial fluid gelatinase (MMP-2 and -9) expression and activity was assessed by gelatin zymography. Results MMP-1 and MMP-9 expression was enhanced in both stable asthma and during asthma exacerbations, whilst MMP-2 expression was only increased during asthma exacerbations. MMP-1 can be activated by tryptase, which is an inflammatory product of mast cell degranulation. Activated (degranulated) mast cells enhanced proliferation of both control and asthma ASM cells via the production of a pro-proliferative ECM in vitro and the proliferative effect was dependent on MMP-1. In patients with asthma, mast cells numbers within ASM bundles were associated with ASM growth. MMP-1 protein levels were related to bronchial reactivity and MMP-1 activity increased during asthma exacerbations, where its levels were related to exacerbation severity. Conclusion This study suggests that MMP-1 plays an important role in asthma pathophysiology and that ASM/mast cell interactions contribute to asthma severity by transiently increasing MMP-1 activation, ASM growth and airway responsiveness. Moreover, there is increased expression of MMP-2 and -9 during asthma exacerbations compared with stable asthma. As both MMP-2 and -9 act as mediators of inflammation (Okada, S. et al., 1997) (Elkington, P.T.G., 2006) and tissue remodelling (Oshita, Y. et al., 2003), an increase in gelatinolytic activity linked to MMP-2 and MMP-9 is also likely to play a significant role in the pathophysiology of asthma exacerbations.
27
Kheirallah, Alexander K. "A genome-wide regulatory network of INTS12 associated with pulmonary function." Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/40605/.
Full textAbstract:
Genome-wide association studies of human lung function and Chronic Obstructive Pulmonary Disease have identified a highly significant and reproducible signal on 4q24. It remains unclear which of the two candidate genes within this locus may regulate lung function: GSTCD, a gene with unknown function, and/or INTS12, a member of the Integrator Complex which is currently thought to mediate 3’end processing of small nuclear RNAs. An interrogation of bioinformatic datasets showed that in lung tissue, 4q24 polymorphisms associated with lung function correlate with INTS12 but not neighboring GSTCD expression. In contrast to the previous reports in other species, a minor alteration of small nuclear RNA processing was observed following INTS12 depletion. RNA sequencing analysis of knockdown cells instead revealed dysregulation of a core subset of genes relevant to airway biology and a robust downregulation of protein synthesis pathways. Consistent with this, protein translation was decreased in INTS12 knockdown cells. In addition, chromatin immunoprecipitation and sequencing experiments demonstrated INTS12 binding throughout the genome, which was enriched in transcriptionally active regions. Finally, INTS12 regulome was defined which includes genes belonging to the protein synthesis pathways. INTS12 has functions beyond the canonical snRNA processing and evidence is presented showing that it regulates translation by directly controlling the expression of genes belonging to protein synthesis pathways. This thesis provides a detailed analysis of INTS12 activities on a genome-wide scale and contributes to the understanding of biology behind the genetic association for lung function at the 4q24.
28
Hutchinson, John. "International comparative epidemiology of idiopathic pulmonary fibrosis." Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/40715/.
Full textAbstract:
Background Evidence from the UK suggests the incidence of idiopathic pulmonary fibrosis is increasing, but there is a lack of data from elsewhere in the World. The cause of the disease remains unknown. New anti-fibrotic therapies may increase the use of surgical lung biopsy for accurate diagnosis, although the risks of this (and other surgery) are not clear. Methods Collated international mortality statistics and a systematic review of the literature were used to assess the incidence and mortality of idiopathic pulmonary fibrosis worldwide. Primary care data from the United Kingdom were used to assess the association between recent major surgery and a new diagnosis of idiopathic pulmonary fibrosis. Secondary care data from the United States and United Kingdom were used to assess the risk of surgical lung biopsy for the diagnosis of interstitial lung disease, and the risk of other major surgery in those with idiopathic pulmonary fibrosis. Results Mortality from idiopathic pulmonary fibrosis in increasing steadily worldwide. Incidence varies worldwide but is in the range of 3-9 per 100,000 in the West. No association was identified between recent major surgery and a new diagnosis of idiopathic pulmonary fibrosis. Surgical lung biopsy for the diagnosis of interstitial lung disease has an in-hospital mortality of under 2% for elective procedures, but this is higher for non-elective surgery, and in those who are older with co-morbidities. In those with idiopathic pulmonary fibrosis undergoing major surgery, in-hospital mortality was higher than the general population. Conclusion Idiopathic pulmonary fibrosis seems to be increasingly common worldwide. Surgery has risks, particularly in unwell older patients, and less invasive diagnostic methods are needed.
29
Popov, Plamen Atanassov. "Accuracy problems in weighing vehicles in motion." Thesis, City University London, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.386013.
Full text
30
Khaleghi, Farideh. "Erbium-doped fiber amplifier applications in WDM transport systems and networks." Thesis, University of Ottawa (Canada), 1996. http://hdl.handle.net/10393/10194.
Full textAbstract:
New expressions are derived for wavelength-dependent gain variations of the EDFA due to changes in the pump power, total input power, and the power distribution among different wavelength channels in a wavelength-division multiplexing (WDM) system. A simple method is proposed to compensate for the changes in the amplifier gain spectrum. This method is based on adjusting the pump power. Two different novel gain equalization techniques are presented. A tunable coherent optical transversal filter is designed as a gain equalizer. The filter operation is based on coherently combining the tapped signals. It is shown that, although the N tapped signals after being weighted according to the filter parameters are recombined by a tree of 2 x 2 couplers, the coupling loss experienced at the output is much less than the noncoherent coupling loss (10log(N)). For a multi-wavelength input, the spectrum of the amplifier output power is evaluated before and after the equalizer, using the numerical full spectrum model of the amplifier. The impact of the laser phase noise on the performance of this equalizer is studied. Another gain equalization technique is presented where high- and moderate-inversion EDFAs are used alternatively in order to equalize both signal power and signal-to-noise ratio (SNR) of multiple wavelength channels in WDM transmission systems. This technique is based on the fact that the gain slope is a function of the inversion level in amplifiers. This is confirmed experimentally. The performance of the equalized WDM system is examined by a numerical analysis based on the full spectrum model of the amplifier. The interferometric conversion of the phase-to-intensity noise is studied. The probability density function (pdf) of the intensity noise at the output of a multi-tap filter is derived. The degradation of the filter response is evaluated. The power penalty due to this noise is derived for amplitude modulated signals modulated using different bit rates. The power penalty due to interferometric noise caused by multiple reflections is also derived. A novel bidirectional EDFA configuration is proposed where the power penalty associated with the amplifier due to both the signal-spontaneous noise and the interferometric noise is substantially reduced. The experimental results are presented where a gain of 36 dB is achieved, and a 2.5 Gb/s bidirectional transmission over 300 km is realized. The power penalty is as low as 0.5 dB. Application of EDFA in an optical network is presented. The multi-access scheme in this local network is code-division multiple access (CDMA). A new correlator receiver architecture for noncoherent optical CDMA networks is proposed based on a modified version of unipolar-bipolar correlation functions for known bipolar codes. These functions are studied. Average bit error rate (BER) performance is evaluated for this architecture. The results indicate that bipolar capacity can be achieved by this architecture.
31
Arya, Vivek. "Analysis, Design and Performance Evaluation of Optical Fiber Spectrum-Sliced WDM Systems." Diss., Virginia Tech, 1997. http://hdl.handle.net/10919/30584.
Full textAbstract:
This dissertation investigates the design and performance issues of a recently demonstrated technique, termed as spectrum-slicing, for implementing wavelength-division-multiplexing (WDM) in optical fiber systems. Conventional WDM systems employ laser diodes operating at discrete wavelengths as carriers for the different data channels that are to be multiplexed. Spectrum-slicing provides an attractive low-cost alternative to the use of multiple coherent lasers for such WDM applications by utilizing spectral slices of a broadband noise source for the different data channels. The principal broadband noise source considered is the amplified spontaneous emission (ASE) noise from an optical amplifier. Each slice of the spectrum is actually a burst of noise that is modulated individually for a high capacity WDM system. The stochastic nature of the broadband source gives rise to excess intensity noise which results in a power penalty at the receiver. One way to minimize this penalty, as proposed and analyzed for the first time in this work, is to use an optical preamplifier receiver.
It is shown that when an optical preamplifier receiver is used, there exists an optimum filter bandwidth which optimizes the detection sensitivity (minimizes the average number of photons/bit) for a given error probability. Moreover the evaluated detection sensitivity represents an order of magnitude ( > 10 dB) improvement over conventional PIN receiver-based detection techniques for such spectrum-sliced communication systems. The optimum is a consequence of signal energy fluctuations dominating at low values of the signal time bandwidth product (m), and the preamplifier ASE noise dominating at high values of m. Operation at the optimum bandwidth renders the channel error probability to be a strong function of the optical bandwidth, thus providing motivation for the use of forward error correction coding (FEC). System capacity (for BER = ) is shown to be 23 Gb/s without coding, and 75 Gb/s with a (255,239) Reed Solomon code.
The effect of non-rectangular spectra on receiver sensitivity is investigated for both OOK and FSK transmission, assuming the system (de)multiplexer filters to be N'th order Butterworth bandpass. Although narrower filters are recommended for improving power budget, it is shown that system penalty due to filter shape may be kept < 1 dB by employing filters with N > 2. Moreover spectrum-sliced FSK systems using optical preamplifier receivers are shown, for the first time, to perform better in a peak optical power limited environment. Performance-optimized spectrum-sliced WDM systems have potential use in both local loop and long-distance fiber communication systems which require low-cost WDM equipment for high data rate applications.Ph. D.
32
McPherson, Amy. "Understanding asthma : a study to evaluate the impact of an educational computer program on children's knowledge and selfmanagement skills." Thesis, University of Nottingham, 2003. http://eprints.nottingham.ac.uk/10338/.
Full textAbstract:
Childhood asthma is an extensive problem and is particularly pronounced in the UK. Asthma can restrict activities, cause school absence and can be the source of considerable stress in both children and their parents. Mortality is rare and preventable, although poor perception of symptoms and delay in seeking medical attention are strong risk factors for a fatal asthma attack. Self- management actively involves the child in their own healthcare and entails monitoring symptoms and responding accordingly and has been linked to better outcomes. This can be facilitated by health education. The aims of this project were to develop an educational computer program to promote self-management skills in children and young people with asthma, to evaluate its effectiveness in a clinical sample and to validate measures of asthma knowledge and locus of control. The Asthma Files uses a 'secret agent' theme to encourage users to investigate information about asthma. The program was piloted with 28 children aged 7-16 over a one year period and revised in accordance with both qualitative and quantitative data obtained. To evaluate the computer program, 101 children aged between 7 and 14 years were recruited from three hospital asthma out-patient clinics to participate in a randomised, controlled trial. They were interviewed using asthma knowledge and asthma-specific locus of control measures developed and validated for the purposes of the study. All children were given an information booklet one month later and, in addition, 50 children used the computer program. Baseline knowledge levels were low. At one-month follow-up (n=99), children in the computer group had significantly greater increases than those in the control group (p<0.001), along with an rise in internal locus of control(p<0.01). There was no evidence of changes in objective lung function measures, hospitalisations or oral steroid use between the groups at this time. However, at six months follow-up (n=90), children in the computer group were significantly less likely to have required oral steroids or school absence than the control group (p<0.05). The program was popular with the children across the age range and received positive feedback on both content and mode of delivery. Responding to comments provided by the children in the RCT, some minor amendments were made to the program, which is now available for public use. The Asthma Files computer program was successful in increasing knowledge and promoting internal locus of control. More research is needed to evaluated how this might translate into longer term improvements in self-management. NB. This ethesis has been created by scanning the typescript original and may contain inaccuracies. In case of difficulty, please refer to the original text.
33
Binnion, Amy Margaret. "Regulation of chemokine expression in human airway smooth muscle cells." Thesis, University of Nottingham, 2010. http://eprints.nottingham.ac.uk/11344/.
Full textAbstract:
Asthma is an inflammatory disease of the airways characterised by airway remodelling and hyperresponsiveness. New treatments are needed for patients with severe asthma whose disease is not controlled with currently available therapies. Asthma pathophysiology is complex, however, accumulating evidence suggests multiple inflammatory pathways in asthma converge onto a relatively small number of downstream targets that may be of therapeutic interest. These include mitogen activated protein kinases (MAPKs), the pro-inflammatory transcription factors nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) and transcriptional regulators such as histone acetyl transferases (HATs) and histone deacetylases (HDACs). Chemokines are molecules secreted at sties of inflammation, attracting inflammatory cells and perpetuating the inflammatory response. Here we studied the mechanisms by which the pro-inflammatory mediator endothelin-1 (ET-1) and the cytokine tumour necrosis factor-alpha (TNF-alpha) promoted expression by primary human airway smooth muscle cells (HASMC) of two important chemokines, monocyte chemotactic protein-1 (MCP-1) and eotaxin. Further, we studied the mechanisms by which existing asthma therapies (long acting beta agonists (LABA) and glucocorticoids) modulated TNF-alpha-stimulated eotaxin expression. Endothelin-1 stimulated MCP-1 release through a transcriptional mechanism involving NF-kappaB and AP-1; the upstream signalling pathway involved p38 and p44/p42 MAPKs. Previously, this lab showed that TNF-alpha-induced eotaxin release is also NF-kappaB-dependent, involving histone H4 acetylation at the eotaxin promoter. Here we found that TNF-alpha-induced eotaxin release does not involve histone H3 acetylation, and that TNF-alpha-dependent histone H4 acetylation does not occur through alterations in total histone activity or levels of the key HDACs -1 and -2. Similarly, modulation of TNF-alpha effects on eotaxin expression by glucocorticoids and LABA is independent of total HDAC activity and HDAC-1 and -2 levels. These studies support the body of evidence suggesting that multiple inflammatory pathways in asthma converge onto a small number of downstream targets, and are relevant to the understanding and treatment of asthma.
34
Tatler, Amanda Louise. "Mechanisms of transforming growth factor-β activation in airway smooth muscle cells and its role in asthma." Thesis, University of Nottingham, 2010. http://eprints.nottingham.ac.uk/13653/.
Full textAbstract:
Asthma is a chronic inflammatory disease of the airways characterised by airway hyper-responsiveness (AHR), inflammation of the airways and reversible airway obstruction. Airway remodelling is a feature of asthma, especially in cases of severe and fatal asthma, and includes structural changes such as increased airway smooth muscle (ASM) mass, mucous gland hyperplasia, subepithelial fibrosis and angiogenesis. TGF-β is a pleiotropic cytokine that has been implicated in the development of many of these changes. However, TGF-β is released from cells in a latent complex, associated with its pro-peptide the latency associated peptide (LAP). Extracellular activation of latent TGF-β is the rate limiting step in TGF-β bioavailability. Although TGF-β activation has been investigated in airway epithelial cells, to date, no studies have investigated TGF-β activation by airway smooth muscle cells. The hypothesis of this thesis is therefore that human airway smooth muscle cells can activate TGF-β in vitro. The hypothesis of this thesis has been tested by investigating effects of the serine protease mast cell tryptase, mechanical wounding of cell mono layers and the phospholipid lysophosphatidic acid (LPA) on TGF-β activation by primary airway smooth muscle cells in vitro. We have utilised transformed mink lung epithelial cells, a reporter cell that express a TGF-β responsive promoter driving a luciferase gene, and quantitative PCR for the TGF-β-inducible gene plasminogen activator inhibitor-1 (PAI1) to investigate TGF-β activation. Moreover, we show for the first time that TGF-β activation can be assessed in vitro by detecting the translocation of Smad 2 and 3 from the cytoplasm to the nucleus by western blotting. The results presented in this thesis provide evidence that airway smooth muscle cells are capable of activating TGF-β in vitro. These data show that the serine protease tryptase, released from activated mast cells, can proteolytically activate TGF-β via a mechanism that is independent of the tryptase receptor protease activated receptor-2 (PAR2). This effect is not accompanied by increased expression of the latent TGF-β complex. Furthermore, these data provide evidence that airway smooth muscle cells can activate TGF-β via the integrin αβV5 in response to LPA stimulation. We have found that cells from asthmatic patients activate more TGF-β in response to LPA than cells from non-asthmatic individuals and this is not due to a difference in cell surface expression levels of the αβV5 integrin. LPA-induced TGF-β activation can be inhibited by the β2 adrenoreceptor agonist formoterol, which is a commonly used asthma therapy, and the muscarinic receptor agonist methacholine, which causes cell contraction, also causes TGF-β activation by airway smooth muscle cells. Furthermore, the data presented here show that the cytoplasmic domain of the integrin β5 subunit interacts with the cytoskeletal protein talin to mediate TGF-β activation. Together, these data highlight two previously unreported, biologically relevant, mechanisms of TGF-β activation employed by airway smooth muscle cells in vitro, both of which could contribute to the development of airway remodelling in asthma in vivo. Data concerning a αβV5 mediated TGF-β activation has led us to hypothesise that contraction of airway smooth muscle leads to TGF-β activation in vivo. If correct, this could be vital to our understanding of how airway remodelling is initiated in asthma, and could lead to the development of new therapies aimed at inhibiting contraction-induced TGF-β activation, for the treatment of asthma.
35
Whale, Christopher Ian. "Safety aspect of β2-agonists in chronic obstructive pulmonary disease." Thesis, University of Nottingham, 2009. http://eprints.nottingham.ac.uk/10647/.
Full textAbstract:
Chronic Obstructive Pulmonary Disease (COPD) presents an enormous public health challenge. Cigarette smoking remains the most important aetiological factor and although legislation to reduce smoking has been introduced in parts of the more developed world, consumption is increasing in many of the poorest parts of the world. With the predicted rise in disease prevalence, COPD is expected to become the worlds third largest cause of death by 2020. COPD is a disease state characterised by airflow limitation that is not fully reversible. Inhaled bronchodilators can only produce a small improvement in the airflow obstruction, but despite this, patients with COPD frequently use high doses of beta-2-agonists as the disease progresses and they develop breathlessness and exercise limitation. Short-acting beta-2-agonists are generally used as required to reduce breathlessness and reduce airflow obstruction whereas long-acting beta-2-agonists are prescribed on a regular twice-daily basis to reduce symptoms and rescue medication use and because of a potential beneficial effect on quality of life and exacerbation rates. Although generally well tolerated, the safety of inhaled beta-2-agonists has been a source of some concern since the late 1960s, when an epidemic of asthma deaths was associated with the use of a high dose formulation of isoprenaline. Further controversy has followed and questions have extended to long-acting beta-2-agonists, most notably after a recent large-scale post marketing surveillance study identified an association between the regular use of inhaled salmeterol and asthma-related deaths. The safety of inhaled beta-2-agonists is also an important consideration for patients with COPD. Being older and likely to have a history of cigarette consumption means that they are at risk of having symptomatic, or subclinical, ischaemic heart disease. Beta-2-agonists cause a number of systemic effects including an increase in heart rate, transient hypoxaemia and hypokalaemia. Since many patients with COPD are already hypoxaemic and may be taking other drugs that stimulate the myocardium and cause hypokalaemia, the additional systemic effects from beta-2-agonists may be more likely to produce adverse cardiac events including dysrhythmia and ischaemia. This thesis is concerned with the safety of inhaled beta-2-agonists in the management of COPD. The introduction consists of an overview of the epidemiology, natural history and pathology of COPD (Chapter 1) and a review of human beta-2-adrenoceptor function and inhaled beta-2-agonist pharmacology (Chapter 2). This is followed by a systematic literature review of the results from long-term clinical studies of inhaled beta-2-agonists in subjects with COPD (Chapter 3). The original work consists of three clinical studies that have examined aspects of the effect of high dose inhaled beta-2-agonists in subjects with COPD and a discussion to place these findings in context. Most published studies of inhaled beta-2-agonists in subjects with COPD have focused on their efficacy, rather than safety. We were concerned that some individuals with COPD and limited bronchodilator reversibility may experience an increase in adverse systemic effects after inhaling high doses of beta-2-agonists, which could lead to detrimental outcomes in certain clinical situations. Apart from the cardiac effects mentioned above, beta-2-agonists increase tremor, which causes CO2 production, and cardiac output and tissue perfuson, which increases the transport of CO2 to the lungs. The increase in CO2 flux to the lungs will normally increase ventilation. We were concerned however that some subjects with severe COPD would not be able to increase ventilation appropriately in response to the beta-2-agonist and this would lead to an increase in PaCO2. Our hypothesis was that high dose inhaled beta-2-agonists could worsen respiratory failure in some subjects with severe COPD. The first two studies in the thesis examined the effect of high dose inhaled salbutamol on the partial pressure of arterial oxygen and carbon dioxide in subjects with severe COPD. We initially conducted a double blind, randomised study on subjects within 48 hours of being admitted to hospital with an acute exacerbation of COPD (Chapter 4). The study was designed to determine whether high dose salbutamol caused an increase in the partial pressure of arterial carbon dioxide. We randomised subjects at a ratio of 3:1 to receive either salbutamol or ipratropium bromide and studied the pharmacodynamic effect on heart rate, PaO2 and PaCO2 over five hours. Over eighteen months and despite extensive efforts I was only able to recruit ten subjects, of whom five completed the study. I found that subjects who required hospital admission with an acute exacerbation of COPD were either too unwell for the study, had co-morbidities that precluded participation or the individuals were unwilling to participate. Although the study was terminated prematurely and we were unable to perform statistical analysis, I have presented the findings from the five subjects who completed the study, of whom four were randomised to receive salbutamol. We used ascending doses of salbutamol (1.25mg, 1.25mg, 25mg, 5mg, 5mg) and found no consistent effect on PaCO2 or PaO2 and no dose response relationship. The subject with the highest baseline PaCO2 did however have a rise in PaCO2 with the highest 5mg doses of salbutamol. To test the hypothesis further we conducted a randomised, double blind, crossover study and examined the effect of salbutamol on the arterial blood gas tensions of fourteen patients with stable severe COPD and a history of chronic or intermittent hypercapnia. The study was designed to determine whether high dose salbutamol causes a rise in PaCO2 when inhaled by subjects with severe COPD and a history of alveolar hypoventilation. We compared the effect of two 5mg doses with two 200 microgram doses of salbutamol on PaO2 and PaCO2 and heart rate. The subjects had severe COPD with a mean FEV1 of 0.71 L (27% predicted) and a mean smoking history of 53 pack years. The mean baseline PaO2 was 7.9 kPa and the mean baseline PaCO2 was 7.0 kPa. The high dose of salbutamol caused a mean fall in both PaO2 and PaCO2 and a small increase in heart rate. There was some support for our hypothesis however as three subjects had a small rise in PaCO2 after high dose nebulised salbutamol (Chapter 5). The third study was a double blind, crossover, dose-response examination of the bronchodilator and systemic effects of inhaled formoterol in subjects with COPD (Chapter 6). The rapid onset and prolonged duration of action of formoterol offers potential for the drug to be used as rescue medication in addition to twice daily maintenance therapy, as is the case in the management of asthma. Our hypothesis was that high doses of formoterol would produce adverse systemic effects that would outweigh the beneficial bronchodilator effects in subjects with COPD and limited bronchodilator response to salbutamol. We studied 20 subjects, with a mean FEV1 of 1.32 L (47% predicted) and a mean smoking history of 42 pack years. Each subject was studied on five days and after receiving placebo, formoterol 6, 12, 24 and 48 mg in a random sequence, we examined the effect of each dose on FEV1, tremor, dyspnoea, heart rate, blood pressure, SpO2, walk distance, potassium and satisfaction. We found that all doses were well tolerated and although there was a small dose related increase in FEV1 and the mean satisfaction scores were higher with each dose of formoterol than placebo, there was no dose related improvement in measures that are important to the patient, including breathlessness and walk distance. Apart from a dose related increase in tremor, other systemic effects were limited. All three studies found that high dose inhaled beta-2-agonists produced relatively modest systemic effects in subjects with COPD.
36
Dodor, Emmanuel Atsu. "An exploration of the causes, manifestations and consequences of tuberculosis stigma in an urban district in Ghana." Thesis, University of Nottingham, 2009. http://eprints.nottingham.ac.uk/10846/.
Full textAbstract:
This thesis used a qualititave research approach to explore the causes, manifestations and consequences of tuberculosis (TB) stigma in an urban district in Ghana. It examined reasons why TB is stigmatised and elucidated how TB stigma manifests within the community setting and the healthcare system. It also explored the feelings and experiences of TB patients, to highlight how the fear of stigmatisation may affect case finding and treatment adherence. Twenty eight focus groups (6 with patients, 6 with health workers and 16 with community members) and 121 individual interviews (66 with community members, 34 with patients and 21 with health staff) were conducted. Data were analysed using Grounded Theory techniques and procedures. Eleven causes of TB stigma were identified: fear of infection; physical frailty of TB patients; association of TB with HIV/AIDS; perceived causes and spread of TB; outdated societal practices about TB; public health practice and discourse; attitudes of healthcare workers towards TB patients; health staff’s own fear of TB; self-stigmatisation by TB patients; judgement, blaming and shaming TB patients; and past experiences with TB. Elements of physical and moral threats were identified in all these causes of TB stigma. The threat the disease poses to community members led to imposition of socio-physical distance, participatory restrictions and rules for unexpected interactions on those suffering from TB in society. Within the healthcare system, the threat of TB affected the attitudes and behaviours of healthcare workers towards TB patients and TB work. Health managers also sited TB units/wards in isolated parts of the hospital, and failed to provide adequate tools and equipment, support and supervision to enable the provision of quality TB services. The fear of stigmatisation made the patients deny the obvious symptoms of the disease, and report to the hospital only after prolonged period of self-medication in the community. When diagnosed, they cried, questioned how they got the disease, contemplated committing suicide and were mostly isolated within the family and community. For everyone, the threat of TB underlies their beliefs, attitudes, actions and behaviours when interacting with TB patients. It also forms the basis of avoidance of social interactions, and attitudes and practices of healthcare workers towards TB patients. The TB control programme should encourage open discussion about TB in the community and tailor health education messages to the community’s understanding of the disease. TB services should be completely integrated into the general healthcare system and community members involved in activities of the TB control programme. Regular refresher courses in TB control and management should be organised for health professionals and a national guideline for the prevention of TB in health workers developed.
37
Patel, Mitesh Dilipkumar Kantilal. "Efficacy and safety of maintenance and reliever combination budesonide/formoterol therapy in asthma patients at risk of severe exacerbations : a randomised controlled trial." Thesis, University of Nottingham, 2013. http://eprints.nottingham.ac.uk/13591/.
Full textAbstract:
The Single combination budesonide/formoterol inhaler as Maintenance And Reliever Therapy (SMART) regimen reduces severe asthma exacerbations, but it is uncertain whether it increases the risk of adverse effects due to high corticosteroid and beta-agonist doses with both short-term and cumulative exposure in patients at risk of severe exacerbations. The primary hypothesis was that the SMART regimen would reduce the risk of beta-agonist overuse. Secondary aims were to investigate whether patients treated with the SMART regimen were less likely to seek medical review in the setting of beta-agonist overuse and to determine whether any reduction in severe asthma exacerbations would be at a cost of a higher systemic corticosteroid burden. This 24-week, open-label, parallel-group, multicentre randomised controlled trial randomised 303 asthma patients with a recent exacerbation to combination 200/6µg budesonide/formoterol metered dose inhaler (MDI) according to the SMART regimen (two actuations twice daily as maintenance with one extra actuation as-needed for relief of symptoms) or a fixed-dose regimen (two actuations twice daily as maintenance) with one to two actuations of 100µg salbutamol MDI as-needed for relief of symptoms (the ‘Standard’ regimen), with electronic monitoring to measure actual medication use. The use of electronic monitoring allowed beta-agonist overuse to be applied as a marker of the risk of life-threatening asthma. The primary outcome was the proportion of participants with at least one high beta-agonist use episode (more than eight actuations per day of budesonide/formoterol in addition to the four maintenance doses in the SMART group or more than 16 actuations per day of salbutamol in the Standard group). There was no significant difference between groups in the proportion of participants with at least one high use episode: SMART 84/151 (55.6%) versus Standard 68/152 (44.7%), relative risk (95% CI) 1.24 (0.99 to 1.56), p=0.058. There were fewer days of high use in the SMART group [mean (SD) 5.1 days (14.3) versus 8.9 days (20.9), relative rate (95% CI) 0.58 (0.39 to 0.88), p=0.01]. Of the participants who had at least one high use episode, those in the SMART group had fewer days of high use without medical review [mean (SD) 8.5 days (17.8) versus 18.3 days (24.8), relative rate (95% CI) 0.49 (0.31 to 0.75), p=0.001]. The SMART regimen resulted in higher inhaled corticosteroid exposure [mean (SD) 943.5µg budesonide per day (1502.5) versus 684.3µg budesonide per day (390.5), ratio of means (95% CI) 1.22 (1.06 to 1.41), p=0.006], but reduced oral corticosteroid exposure [mean (SD) 77.5mg prednisone (240.5) versus 126.6mg prednisone (382.1), p=0.011], with no significant difference in composite systemic corticosteroid exposure [mean (SD) 793.7mg prednisone equivalent per year (893.1) versus 772.1mg prednisone equivalent per year (1062.7), ratio of means (95% CI) 1.03 (0.86 to 1.22), p=0.76]. Participants in the SMART group had fewer severe asthma exacerbations [35 (weighted mean rate per year 0.53) versus 66 (0.97), relative rate (95% CI) 0.54 (0.36 to 0.82), p=0.004]. The SMART regimen has a favourable risk/benefit profile in patients at risk of severe asthma exacerbations. Funding This study was funded by the Health Research Council of New Zealand, a government funding organisation.
38
Pogson, Zara. "The effect of sodium on cardio-respiratory health." Thesis, University of Nottingham, 2009. http://eprints.nottingham.ac.uk/10626/.
Full textAbstract:
Background This thesis investigates the effect of sodium modification on asthma and heart rate variability (HRV) using a randomised controlled study design. Cross-sectional data were used to assess novel markers of asthma control and if serum osmolality was inversely associated with lung function. Methods and Results The effect of dietary sodium modification on asthma control and HRV The study design was a randomised placebo-controlled double-blind study of participants aged 18-65 years old with asthma and measurable bronchial reactivity. The intervention involved adopting a low sodium diet for six weeks. 199 participants provided measures of asthma control and 29 participants provided 24-hour electrocardiographic measurements at baseline and six weeks later. There were no differences between those allocated to the low and normal sodium diet groups in any of the measures of asthma control or HRV. Bronchoconstriction induced by deep inspiration and exhaled carbon monoxide as surrogate marker of asthma control Serial PEFR measures were provided by 127 individuals to measure bronchoconstriction after deep inhalation and 182 individuals provided measurements of eCO. The relationship between these measures and asthma control was assessed. There was no relationship between either bronchoconstriction after deep inspiration or eCO and asthma control. Serum osmolality and lung function The NHANES III database was used to investigate if serum osmolality was cross-sectionally associated with lung function. In 13,602 individuals a SD increase in serum osmolality was associated with a decrease in FEV1 of 19.8ml (95% CI; -30.3 to -9.3) and FVC of 35.3ml (95% CI; -47.9 to -22.7). Conclusions A low sodium diet did not improve asthma control or increase heart rate variability in adults with asthma. Bronchoconstriction to deep inspiration and measurements of eCO have limited potential as markers of asthma control. In the NHANES dataset, increased serum osmolality was associated with decreased lung function.
39
Feary, Johanna Ruth. "Asthma and allergic disease : their relation with Necator americanus and other helminth infections." Thesis, University of Nottingham, 2012. http://eprints.nottingham.ac.uk/12411/.
Full textAbstract:
Background The rate at which the prevalence of allergic disease is increasing in many countries suggests that environmental exposures may be important aetiological factors. Epidemiological evidence indicates that infection with helminth parasites may be one such factor: in particular, in a systematic review and meta-analysis, current hookworm (Necator americanus) infection at an intensity of 50 eggs/g faeces was shown to be associated with a halving of risk of asthma. The relation between parasite infection and atopy has not been subjected to the same rigorous and comprehensive review. Based on the results of the studies in asthma, it is possible that hookworm infection may have potential in the treatment of this disease, but to date, no clinical trials have been carried out to test this hypothesis. For ethical and safety reasons, before embarking on a clinical trial in asthma it is necessary to establish the dose of larvae required to produce at least 50 eggs/g faeces, and to determine whether experimental hookworm infection might exacerbate bronchial hyper-responsiveness during larval lung migration. Aims and objectives The first aim of this thesis was to establish whether experimental hookworm infection improves asthma by carrying out a series of three intervention studies. The second aim was to determine the association between intestinal parasite infection and atopy (defined as positive allergen skin sensitisation or the presence of specific IgE) and to establish whether the association was species-specific. This thesis therefore consists of two main components: a series of three clinical trials of experimental hookworm infection; and a systematic review and metaanalysis of the association between intestinal parasite infection and atopy. Methods and Results Dose-ranging study of experimental hookworm infection Aim: To identify the dose of hookworm larvae necessary to achieve 50 eggs/g faeces and to monitor any adverse effects of infection. Methods: Ten healthy volunteers, without asthma or bronchial responsiveness to inhaled methacholine, received 10, 25, 50, or 100 Necator americanus larvae administered double-blind to an area of skin on the arm and were monitored weekly for 12 weeks. Results: All doses resulted in the production of at least 50 eggs/g faeces in the eight subjects who completed the study. Skin itching at the entry site and gastrointestinal symptoms were common at higher doses. Study of experimental hookworm infection in allergic rhinoconjunctivitis Aim: To determine whether hookworm larval migration through the lungs increases bronchial responsiveness in allergic individuals with measurable bronchial responsiveness but not clinical asthma, and to investigate the general tolerability of infection and its effect on allergic symptoms. Methods: Thirty individuals with allergic rhinoconjunctivitis and measurable bronchial responsiveness to adenosine monophosphate (AMP) but not clinically diagnosed asthma were randomised, double-blind, to cutaneous administration of either ten Necator americanus larvae or histamine placebo, and followed for 12 weeks. The primary outcome was the maximum fall from baseline in provocative dose of inhaled AMP required to reduce one-second forced expiratory volume by 10% (PD10AMP) measured at any time over the four weeks after active or placebo infection. Secondary outcomes included peak flow variability in the four weeks after infection, adverse effect diary scores and rhinoconjunctivitis symptom severity over the 12-week study period, and change in allergen skin sensitisation between baseline and 12 weeks. Results: Mean maximum change in PD10AMP from baseline was slightly but not significantly greater in the hookworm than the placebo group (-1.67 and -1.16 doubling doses; mean difference -0.51, 95% confidence interval: -1.80 to 0.78; p=0.42). There were no significant differences in peak flow variability, rhinoconjunctivitis symptoms or allergen skin sensitisation between groups. Symptom scores of potential adverse effects were more commonly reported in the hookworm group, but infection was generally well tolerated. Study of experimental hookworm infection in asthma Aim: To determine the effects of experimental hookworm infection on asthma. Methods: Thirty-two individuals with asthma and measurable bronchial hyperresponsiveness to adenosine monophosphate (AMP) were randomised, doubleblind, to cutaneous administration of either ten Necator americanus larvae or histamine placebo, and followed for 16 weeks. The primary outcome was the change in provocation dose of inhaled AMP required to reduce one-second forced expiratory volume by 20% (PD20AMP) from baseline to week 16. Secondary outcomes included change in several measures of asthma control and allergen skin sensitisation and the occurrence of adverse effects. Results: Mean PD20AMP improved in both groups, more in the hookworm (1.49 doubling doses (DD)) than the placebo group (0.98 DD), but the difference between groups was not significant (0.51 DD, 95% confidence interval: -1.79 to 2.80; p=0.65). There were no significant differences between the two groups for other measures of asthma control or allergen skin sensitisation. Infection was generally well tolerated. Systematic review and meta-analysis of the association between intestinal parasite infection and atopy Aim: To quantify the association between current intestinal parasite infection and the presence of atopy in a systematic review and meta-analysis of epidemiological studies, and to determine whether, as with asthma, this relation is species-specific. Methods: MEDLINE, EMBASE, LILIACS and CAB Abstracts (to March 2009); reviews; and reference lists from publications were searched. No language restrictions were applied. Studies that measured current parasite infection using direct faecal microscopy and defined atopy as allergen skin sensitisation or presence of specific IgE were included. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) using data extracted from published papers using random effect models were calculated. Results: 20 studies met the inclusion criteria. Current parasite infection was associated with a reduced risk of allergen skin sensitisation (OR 0.69, 95% CI: 0.60 to 0.79; p<0.01). When analyses were restricted to current geohelminth infection, the size of effect remained similar (OR 0.68, 95% CI: 0.60 to 0.76; p<0.01). In species-specific analysis, a consistent protective effect was found for infection with Ascaris lumbricoides, Trichuris trichiura and hookworm. There were insufficient data to pool results for chistosomiasis or atopy defined by presence of specific IgE. Conclusions Experimental infection with ten Necator americanus larvae produces at least 50 eggs/g faeces, the intensity of infection seen to protect against asthma in observational studies. This dose is safe, well tolerated, feasible to use in clinical trials and does not cause clinically significant exacerbation of bronchial responsiveness during larval pulmonary migration. In clinical trials, it did not result in significant improvement in symptoms of allergic rhinoconjunctivitis, or in bronchial hyper-responsiveness or other measures of asthma control. However, a non-significant improvement in bronchial hyper- responsiveness was seen, indicating that further studies incorporating revised dosing regimens that more closely mimic natural infection are feasible, and should be undertaken, with the aim of identifying novel treatments for asthma. As with asthma, there appears to be an inverse association between intestinal parasite infection and atopy. Work should continue to identify the mechanisms of this effect and means of harnessing these to reduce the global burden of allergic disease.
40
Yanney, Michael Peter. "Continuous negative extrathoracic pressure and bronchiolitis." Thesis, University of Nottingham, 2008. http://eprints.nottingham.ac.uk/10458/.
Full textAbstract:
Bronchiolitis is the commonest cause of acute respiratory failure in infancy and several hundred children need respiratory support for the condition each year in the United Kingdom. Continuous negative extrathoracic pressure (CNEP) has been used to support such children but concerns about its possible association with significant harm prompted a government enquiry into the conduct of research at a UK centre using the technique. This retrospective study was designed to address these concerns by careful evaluation of outcome in two matched cohorts. Fifty children who had received CNEP for bronchiolitis as infants were compared with 50 controls who were treated in another hospital during the same period. Pre-treatment variables, demographics and neonatal factors were well matched in the two groups. In all subjects questionnaires and clinical examination were used to assess respiratory symptoms, disability and health-related quality of life whilst respiratory function was assessed by measuring airway resistance using the interrupter technique (Rint), by spirometry and by bronchodilator responsiveness. CNEP was associated with reduced need for, and shorter duration of, positive pressure ventilation but with longer periods in oxygen and hospital. Median Rint was 16.5% higher in the CNEP cohort (p<0.001) and median FEF25-75 was 9.3% lower (p=0.029). There were no significant differences between the groups in FEV1, FVC, bronchodilator responses or respiratory symptoms, or in the prevalence of moderate or severe disability (Mantel-Haenszel statistic 1.40, 95% confidence intervals: 0.64 -3.04, p=0.39). Median health utility indices were similar; CNEP 1.00 (interquartile range: 0.85-1.00), controls 0.99 (interquartile range: 0.81 -1.00), n=48 pairs, p= 0.37. The higher Rint and lower FEF25-75 in the CNEP group represent a small difference in respiratory function that may be attributable to population differences but a CNEP effect cannot be excluded. Further evaluation of the use of CNEP in bronchiolitis requires a prospective, controlled study.
41
Selvarajah, Senthooran. "The development and application of an antibody microarray as a diagnostic platform for COPD." Thesis, University of Nottingham, 2013. http://eprints.nottingham.ac.uk/13572/.
Full textAbstract:
According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Management Guidelines (2001), the definition of COPD is “a disease state characterised by airflow limitation that is not fully reversible. The airflow is usually progressive and associated with inflammatory responses of the lungs to noxious particles and gases.” It is becoming an increasing prevalent problem worldwide, with the incidences of morbidity and mortality continually increasing and promoting a lower quality of life in individuals that continue to suffer from it. To date, there is still an incomplete understanding of the pathogenesis of the disease resulting in poor diagnosis and treatment plans for COPD that are insufficient in preventing a decline in lung function. In recent years, research has focussed on discovering a set of biomarkers that could improve our understanding of pathogenesis of disease. The ability to measure a vast array of biomarkers simultaneously is highly desirable however the cost associated is somewhat prohibitive. Current methods centre on measuring the presence or absence of multiple biomarkers in patient samples compared to controls. As COPD is a multi-component disease which encompasses diseases such as emphysema and chronic bronchitis, it may be necessary to look at biomarker patterns within each disease category. A variety of immune effector cells are known to lead to the pathophysiology of COPD including neutrophils, macrophages and CD8 T-lymphocytes that are all documented to be increased in number and contribute to the inflammatory process. Protein microarrays are used as a measurement tool to determine and quantify the presence or amount of proteins that exist in biological samples (i.e. blood, sputum, [iii] urine etc). The wide use of protein microarray technology has advanced diagnosis and management of multifactorial diseases such as cancer, autoimmunity and allergy. At present, multiple microarray kits are available to researchers at a large cost which make it impractical for most research groups to investigate multiple biomarkers of interest simultaneously. Here we show development, validation and implementation of our bespoke in-house microarray platform enabling quantitative and simultaneous analysis of multiple protein biomarkers at a reasonable cost. The methodology is based on the traditional sandwich ELISA; antibodies are immobilised on poly-L-lysine coated glass and signals amplified and quantified through fluorescence. The accuracy and reproducibility of the in-house microarray was investigated using the guidelines outlined by the Food and Drug Administration (FDA) for pharmacokinetic assay validation. The assay was shown to have high reproducibility with assay accuracy between 80-120% and precision within 20% coefficient of variation, except in very low abundant cytokines such as IL-10, where the CVs were higher due to the variation at the lowest concentrations in sera. Importantly there were no significant differences between ELISA and microarray. This microarray platform was then used to study a selection of healthy controls (n=12), healthy smoking controls (n=36) and COPD patients (n=60) to see if there was a difference in the expression of the 16 biomarkers tested. The overall analysis of the 16 biomarkers investigated in this study, a significant increase in expression of eotaxin-2 was observed in the sera those that have COPD compared to healthy controls and healthy smoking controls. This suggests that eoxtaxin-2 may potentially be responsible for the recruitment and activation of multiple cytokines which in turn lead to the inflammatory cascade observed in COPD COPD severity is divided into four categories according to international guidelines outlined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). This is often known as stage 1 (mild), stage 2 (moderate), stage 3 (severe) and stage 4 (very severe). This is based on the forced expiratory volume per second (FEV-1%). Interestingly when investigating the different severities of GOLD in COPD, it was observed that at the highest stage of GOLD (stage 4), the expression of 15 of the 16 biomarkers had dropped significantly in comparison to the other stages. This may suggest that at this point of the disease process, the immune system may in fact be suppressed in alliance to hypoxia experienced by an individual. Additionally it has to be acknowledged that the medication that the COPD patients were on were not available prior to analysis. It has to be taken into account that patients at GOLD stages 3 and 4 could be likely to be on a high dose of inhaled corticosteroids, which are immunosuppressive which would lead to drop in the 15 cytokines observed. However without the information available, it cannot be definitive to make such conclusions. Hence this work offers an understanding into the development of a bespoke microarray platform that is capable of investigating protein biomarkers in any disease setting.
42
Portelli, Michael A. "The role and regulation of the urokinase receptor in asthma and COPD." Thesis, University of Nottingham, 2013. http://eprints.nottingham.ac.uk/13355/.
Full textAbstract:
The urokinase plasminogen activator receptor (PLAUR) is a membrane anchored receptor that has been associated with a number of disease states. In these diseases, elevated receptor levels were associated with increased disease aggressiveness and higher mortality rates. Through genetic studies PLAUR has been identified as an asthma susceptibility gene. In these studies, coding and untranslated region single nucleotide polymorphisms showed association with asthma diagnosis and decline in lung function. In addition, association with baseline lung function in smokers and PLAUR SNPs was identified. This suggests that PLAUR plays a role in respiratory disease. Work presented in this thesis aimed to i) identify whether serum levels of PLAUR are associated with obstructive lung disease and lung function parameters, ii) identify novel regulatory mechanisms determining PLAUR levels, both at the genetic level in primary bronchial epithelial cells and at the protein level for serum PLAUR, iii) explore a role for the different isoforms in asthma and COPD and iv) determine novel variation in the PLAUR gene and 5` and 3` distal regions through next generation sequencing. Levels of the soluble cleaved form of PLAUR in serum were determined to be significantly elevated in COPD and asthma subjects compared to a control population. This identified an association between the soluble cleaved receptor and disease per se. However, PLAUR levels in serum could not be related to lung function parameters. With regards to receptor regulation, a genome-wide association study identified a novel post-translational PLAUR regulatory mechanism. This involved key SNPs in the human plasma kallikrein gene promoter that directed human plasma kallikrein enzymatic activity to cleave PLAUR in a post-translational mechanism. PLAUR gene regulation was also investigated via molecular biology, identifying that in primary bronchial epithelial cells, PLAUR regulation involves the gene’s 5 prime and 3 prime untranslated regions. Investigation of regulation under multiple stimulations pertinent to respiratory disease identified that cigarette smoke extract selectively elevated the soluble spliced variant of the receptor through a three prime untranslated region mechanism. This suggests that bronchial epithelial damage driven by cigarette smoke may be at least partially mediated by the soluble spliced form of PLAUR. Overexpression of PLAUR identified that the receptor has an important role in regulating primary bronchial epithelial cell function, including migration and rate of mitochondrial activity. Interestingly, results identified isoform specific roles for the different forms of the receptor suggesting that variant-specific over-expression of PLAUR could have diverse effects on cell function. Importantly this study was also the first to define a role for the soluble spliced form of PLAUR. Investigation into variation in the PLAUR gene and surrounding regions through next generation sequencing in asthma (n=200) and control (n=200) populations identified a number of novel variants including 4 variants unique to asthma population. In summary, the work described in this thesis has identified a novel association between serum soluble cleaved PLAUR and obstructive lung disease, as well defining novel genetic and post-translational regulatory mechanisms for PLAUR, importantly defining isoform specific PLAUR regulation for the first time. This work has also identified novel isoform specific roles for PLAUR, which have significant modulatory effects on bronchial epithelial cell function, and has through next generation sequencing furthered knowledge on universal and asthma specific PLAUR variation.
43
Nijmeh, Hala S. "Characterisation of human bronchial epithelial response to injury and identification of potential resident progenitor cells in vitro." Thesis, University of Nottingham, 2009. http://eprints.nottingham.ac.uk/10884/.
Full textAbstract:
As the first line of defence against external stimuli, the airway epithelium undergoes frequent injury during an adult life. This is countered by repair mechanisms that ensure the integrity of the epithelium. It has been established that there are resident stem/progenitor cells localized within specific niches throughout the respiratory tract. Stem/progenitor cells are activated according to the severity of the insult and are thought to be responsible for repairing the airway epithelium. It has been difficult to isolate those stem cells. In this study, an in vitro human bronchial epithelial model was adapted and characterised. In culture, a pseudostratified epithelium was observed, with basal, ciliated, and secretory cells. Mucus production was also seen in this model. A scrape-wound of the model was employed to study the responses of the airway epithelium to injury. It was observed that migration and then proliferation, of CD44 expressing basal cells, are the first events that take place after scrape-wounding. Up-regulation of CD44 was also observed at the edge of the wounds early post-wounding. This suggested a key role for CD44-expressing basal cells in migration and proliferation after wounding, also suggesting this population may contain a progenitor cell population. Investigation of the secretory profile of the airway epithelium post-wounding revealed an increase in a number of cytokines and growth factors. In particular, IL-6, IL-8, ENA-78, and RANTES were all elevated compared with unwounded cultures. A side population (SP) was identified in differentiated and undifferentiated human bronchial epithelial cells in at least some cultures accounting for 0.1-1.15% of cells present. In summary, the epithelium is important in airway wound repair with basal cells appearing to contain the progenitor population in this human bronchial epithelial cell (HBEC) model. Moreover, SP studies suggested the presence of SP in at least some cultures, which might contribute to airway regeneration. The secretory profile of the airway epithelium post-wounding indicates up-regulation of specific cytokines, which may be important in the pathogenesis of lung diseases such as asthma and COPD. This model should prove useful to assess wound repair pathways and may be of use in the future for proof of concept studies on novel therapeutic agents.
44
Rich, Anna. "Validation of the National Lung Cancer Audit database and analysis of the information it contains." Thesis, University of Nottingham, 2012. http://eprints.nottingham.ac.uk/29747/.
Full textAbstract:
Introduction: Lung cancer is the commonest cause of cancer related death in men and women in England. In 2004 the National Lung Cancer Audit (NLCA) was created, as a national non-mandatory contemporary dataset of clinical features of individuals with lung cancer in part to identify variations in clinical practice and outcomes. The main aims of this dissertation are to determine the validity and representativeness of this dataset and then to investigate what factors influence access to surgery and chemotherapy and subsequent survival. In addition I have taken the opportunity afforded by this large dataset to describe the natural history of lung cancer in young adults (20-40 years). Methods: In order to establish if the dataset was representative, I created a measure of case ascertainment at the level of an NHS Trust, and examined the distribution of patient features and outcomes for varying levels of case ascertainment. I have then quantified the impact of patient and NHS Trust level features on access to surgery in people with non-small cell lung cancer and access to chemotherapy in people with small cell lung cancer using multivariate logistic regression. I have also conducted a series of survival analyses using Cox regression. Results: I have found no evidence that patient features vary systematically according to levels of case ascertainment in the NLCA. Age, sex, performance status, stage and co-morbidity all influenced the likelihood of having surgery for people with non-small cell lung cancer. Those patients first seen in a thoracic surgical centre where more likely to receive surgery than patients seen at peripheral centres (adjusted OR 1.51, 95% CI 1.16, 1.97), and surgery had a significant benefit on mortality (adjusted HR 0.41, 95% CI 0.39, 0.44). Although the resection rate was higher for patients first seen at a surgical centre (17% v 12%) these patients did equally well after surgery suggesting they were not a higher risk group. Individuals with small cell lung cancer first seen in a hospital with a high participation in clinical trials, (>5% of expected lung cancer patients being entered into clinical trials), were more likely to receive chemotherapy (adjusted OR 1.42, 95% CI 1.06, 1.90). Chemotherapy was associated with an improvement in survival (adjusted HR 0.51, 95% CI 0.46, 0.56), and amongst those patients receiving chemotherapy, mortality was not affected by the trial status of the hospital where they were first seen. In limited stage small cell disease, those patients who had chemo-radiotherapy had an improved survival compared with those patients who received chemotherapy alone (adjusted HR 0.72, 95% CI 0.62, 0.84). This dataset of English patients with lung cancer contains one of the largest cohorts of young adults (20-40 years) with lung cancer (N=583). I have been able to demonstrate that the majority present with a good performance status (0 or 1 in 80% of those with PS recorded), but advanced (stage IV) disease at diagnosis (55% of those with stage recorded). Those who have surgery have a survival profile similar to their older counterparts. Conclusion: The National Lung Cancer Audit is a representative, contemporary cohort of people with lung cancer, which can provide valuable information for health service research in lung cancer. I have found evidence that there is variation in access to treatment based on the facilities or the performance of individual NHS Trusts. My results suggest that by improving access to thoracic surgery for those individuals with non-small cell lung cancer we may be able to raise the resection rate and improve five year survival. The pattern is similar for people with small cell lung cancer and access to chemotherapy. What this research cannot explain is the aetiology for this variation, and where in the diagnostic pathway changes need to be made to improve the active management and access to potentially curative regimes. As the audit matures with more detailed information on NHS Trust level care, further analyses will be possible to try and determine more clearly what explains these variations, and how we might intervene to reduce them.
45
Amberbir, Alemayehu. "Early life determinants of wheeze and allergic disease : a longitudinal study in an Ethiopian birth cohort." Thesis, University of Nottingham, 2012. http://eprints.nottingham.ac.uk/29714/.
Full textAbstract:
Background: The hypothesis that paracetamol may increase the risk of asthma and other allergic disease has gained consistent support from epidemiological studies, but evidence from longitudinal cohort studies, particularly those looking at the timing and dose of exposure are lacking. Epidemiological studies have also reported an inverse relation between gastro-intestinal infections including Helicobacter pylori, commensal bacteria and geohelminths and asthma and allergic disease, however, data from longitudinal birth cohort study are scarce. This thesis has therefore investigated the effects of paracetamol, H. pylori and other gastro-intestinal infections on the incidence and prevalence of allergic diseases and sensitization in a low-income birth cohort in which confounding by social advantage and other medical interventions is unlikely to play a role. Methods: In 2005/6 a population based cohort of 1065 pregnant women from Butajira, Ethiopia was established, to whom 1006 live singleton babies were born, and these children have been followed-up from birth to age five. At ages one, three and five, the International Study of Asthma and Allergies in Children (ISAAC) questionnaires were administered to the mothers to obtain data on wheeze, eczema and rhinitis. Allergen skin tests to Dermatophagoides pteronyssinus and cockroach were performed at ages three and five. Data on child's use of paracetamol, and various early life putative risk factors, including levels of Der p 1 and Bla g 1 allergen in the child's bedding and symptoms of respiratory tract infections were also measured. Stool samples were collected at ages three and five for analysis of H. pylori antigen using a rapid test (Medimar immunocard), as well as for geohelminths (at ages one, three and five) and selected commensal bacteria (at age three). Multivariate logistic regression was used to determine the independent effects of various markers of paracetamol use on the incidence of each outcome between age one and five, as well as on prevalence at age five. Similar analyses were also carried out to determine the independent effects of H. pylori, geohelminths and commensals on the incidence and prevalence of each outcome. Results: Effects of paracetamol: Of the 1006 children in the cohort at birth, 863 children were successfully followed up at age five (94% of surviving mother-child dyads). Wheeze and eczema incidence between the ages of one and five were reported in 5.9% (40/676) and 5.8% (39/700) of children respectively, and rhinitis and sensitization incidence between ages three and five were found in 3.9% (31/798) and 2.0% (15/766) of children respectively. Paracetamol use in the first three years of life was common, with 18% reported use at age one but not three, 23% at age three but not one and 21% at both time points. Use in the first year of life was significantly associated with a dose-dependent increased risk of incident wheeze between ages one and three (fully adjusted ORs, 95% CI, 1.77; 0.96, 3.26 for 1-3 tablets and 6.78; 1.89, 24.39 for ≥ 4 tablets in past month versus never), but not eczema. The risk of incident wheeze, eczema, rhinitis and sensitization between ages three and five was increased in those exposed, significantly so for incident eczema (p=0.02) and borderline significant for rhinitis (p=0.07), with fully adjusted odds ratios (ORs), including for symptoms of respiratory tract infections, for persistent exposure (ages one and three) versus never of 3.82 (95% CI 1.36, 10.73) and 3.10 (1.00, 9.57) respectively. Borderline significant trends were also seen between paracetamol dose in the first three years of life and incident eczema and rhinitis, with adjusted ORs for heavy reported use compared to low of 1.59 (0.44, 5.74; p trend=0.06) and 2.31 (0.72, 7.46; p trend=0.07) respectively, but not with incident wheeze (fully adjusted OR=3.64; 1.34, 9.90, p trend=0.11). Cross-sectional analysis at age five resulted in significant positive dose-response effects of lifetime use (use at ages one, three and five) in relation to the prevalence of all outcomes. Effects of gastro-intestinal infection H. pylori infection was found in 17% of the children at age three but not five, 21% at age five but not three years, and 25% at both ages. In the longitudinal analysis, H. pylori infection at age three was significantly associated with a decreased risk of incident eczema between ages three and five years (adjusted OR, 95% CI, 0.31; 0.10, 0.94, p=0.02), but the associations with incident wheeze, rhinitis and sensitization were not significant. In cross-sectional analysis at age three, H. pylori infection was associated with a borderline significant reduced risk of eczema (adjusted OR, 95% CI, 0.49; 0.24, 1.01, p=0.05) and D. pteronyssinus sensitization (adjusted OR, 95% CI, 0.42; 0.17, 1.08, p=0.07), and a significant inverse association between current exposure to H. pylori, and any sensitization at age five (adjusted OR, 95% CI, 0.26; 0.07, 0.92, p=0.02). However, no significant associations were seen for wheeze and rhinitis. The prevalence and intensity of geohelminth infection (hookworm, Ascaris lumbricoides and Trichuris trichiura) were found to be low in this cohort, with only 4% of children infected at age one, 9% at age three and only 0.2% at both ages. The risk of new onset wheeze between ages one and three was lower in those infected at age one (3.6%) than uninfected (7.8%), but infection was insufficiently prevalent to compute estimates of effect. Exposure to geohelminth infections in the first three years of life was not significantly associated with the incidence of reported outcomes or sensitization. However, A. lumbricoides infection was associated with a borderline increased risk of incident eczema between ages three and five (adjusted OR, 95% CI, 2.86; 1.04, 7.86, p=0.07). Children at age three were commonly colonized with enterococci 38% (207/544), lactobacilli 31% (169/544) and bifidobacteria 19% (103/544). However, none of these commensal bacteria were associated significantly with either incidence or prevalence of allergic outcomes. Conclusions: This longitudinal study from a developing country birth cohort provides further support for an association between early life use of paracetamol and increased risk of wheeze and allergic disease, which is unlikely to be explained by aspirin avoidance, reverse causation or confounding by indication. Furthermore, among young children in this cohort, the study found novel evidence to support the hypothesis of a protective effect of H. pylori infection on the risk of allergic disease, but no evidence to support an etiological role for the microflora enterococci, lactobacilli or bifidobacteria. The power of the study to explore the role of geohelminth infection on wheeze and allergic disease was limited by few infected children, and therefore understanding on this particular relation has not been much further advanced.
46
Wilson, Emma Elizabeth. "Biomarkers of airway inflammation : the use of exhaled nitric oxide (FeNO) in the management of adult asthma in UK primary care." Thesis, University of Nottingham, 2013. http://eprints.nottingham.ac.uk/29710/.
Full textAbstract:
Rationale: Current asthma guidelines recommend reducing inhaled corticosteroid (ICS) therapy dose by 50% in patients with mild to moderate asthma who have demonstrated three months of good symptom control however there is evidence to suggest that this does not occur. Objectives: We tested whether exhaled nitric oxide (FeNO) measurements or other clinical indices could be utilised to predict a safe reduction of ICS dose, without provoking loss of symptom control or exacerbation within 3 months. We also investigated relationships between airway inflammation and asthma symptoms in the mild to moderate asthma cohort. Methods: 191 patients with stable asthma were recruited from primary care. Patients had their FeNO level measured at baseline and then had their inhaled corticosteroid (ICS) dose reduced by 50%. FeNO measurements were reassessed seven days later. The primary outcomes were whether baseline FeNO or a change in FeNO following ICS dose reduction could predict asthma stability at 3 months. Results: 128/191 patients (67%) completed the ICS dose reduction successfully at three months. 63/191 patients (33%) suffered from either a loss of control or an exacerbation. Baseline FeNO, or change in FeNO (post step-down minus pre step-down) were not statistically significantly different between the two groups. Conclusion: 67% of patients with well-controlled asthma can safely reduce their ICS dose by half without suffering from a loss of control or exacerbation within three months; however neither baseline nor change in FeNO measurements or routine clinical indices can be used to predict which patients can or cannot successfully tolerate a reduction in ICS dose.
47
Lan, Hsiao-Chin, and 藍孝晉. "Grismlens Hybrid WDM System." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/43417504384143943181.
Full text
48
Wen-Shing, Tsai, and 蔡文星. "Crosstalk Reduction in WDM Transport System." Thesis, 2003. http://ndltd.ncl.edu.tw/handle/25887066932076540674.
Full textAbstract:
碩士國立臺北科技大學
光電技術研究所
91
Wavelength division multiplexing(WDM) system can full utilize fiber bandwidth and increase transmission capacity that is the most acceptable structure in recent years. In this thesis, we present improved system performance using dispersion compensation theory. We use chirped fiber gratings(CFGs) as a dispersion compensation device to reduce self phase modulation(SPM) induced chirp、fiber dispersion and cross phase modulation(XPM) induced crosstalk in this article. In addition, we use large effective area fiber(LEAF) to replace traditional single mode fiber(SMF) that can decrease dispersion in the system. Combination with CFGs compare to SMF without CFGs, we can discover improved system performance due to dispersion compensation. Otherwise, we also present hybrid WDM system including different analog and digital signal format that can use SMF and reverse dispersion fiber(RDF) combination as the fiber transmission link to reduce dispersion effect. After long distance transmission, we also can obtain good performance in the system.
49
Liao, Chao-Yi, and 廖昭毅. "Performance Evaluation of Nyquist WDM System." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/23305149402381763053.
Full textAbstract:
碩士國立中山大學
光電工程學系研究所
101
The steadily growing huge demand for capacity in optical fiber communication networks makes a more efficient utilization of the available bandwidth in optical fibers such that increased spectral efficiency is necessary. In order to increase the spectral efficiency in wavelength division multiplexed (WDM) systems, one approach is to reduce the channel spacing between the individual WDM channels. Nyquist WDM systems required to realize the Nyquist bandwidth by using the filter to limit the bandwidth. However, implementing such kind of high precision and narrow Nyquist filters are the challenge and complex technologies. This master thesis intends to utilize the SINC waveform in time domain which is modulated with pseudo random binary sequence (PRBS) to pack the information in the Nyquist bandwidth, and realizes the rectangular spectrum in the frequency domain. It means that it can realize the rectangular spectrum without using any filter to shape the spectrum in the frequency domain.
50
Yu, Neng-Fang, and 余能枋. "Si-based Blazed Grating for WDM System." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/11470880213711217706.
Full text