Tesis por compendio / [EN] New European policies established in the Blueprint (EC, 2012) propose the use of water accounting for the allocation and reservation of water resources. This course correction contrasts with the calculation of water balances that has been used since the last century in Spain for this purpose. According to the European Commission (EC, 2015) the difference between the two approaches is the inclusion of the economic component. This argument is indisputable, but it would also add that both "asset accounts" and the physical supply and use tables require a type of information that had not been considered until now. In view of this new challenge, the use of hydrological and water resources management models is essential. This thesis aims to implement a methodology for the transition between water balances and water accounting considering the special characteristics of the Mediterranean basin (with a high degree of regulation and the use of unconventional resources). In the same line, it raises the need for the definition of an indicator to assess the performance of a water resources system taking into consideration the origin of the water resources as a measure of the degree of stress suffered by the systems. This thesis is presented by publications and seeks to address the methodologies and indicators used to date in the planning and management of water resources. First, the state of the art is analyzed in the first publication of the thesis, as detailed in Annex 1. The second publication, analyzes the key elements for formulating water balances that will determine, to a large extent, results obtained, as detailed in Annex 2. The third publication, in Annex 3, tries to explain how in those basins where the use of water resources is close, or even higher, to their availability, the use of balances based solely on variables such as rainfall and temperature are not sufficient. And due to the high regulation of water resources they should also include the results of water management models. This approach contrasts with the proposals made by the countries of northern Europe focused mainly on hydrological models. In order to address the water accounting approach a pilot case located in the Andalusian Mediterranean basins was analysed. This work is presented in the fourth publication, reproduced in Annex 4. This initial analysis has served to highlight the need to develop a complementary software that allows unify the results of hydrological and water management models for calculating water accounts. The development of this software, which has been called AQUACCOUNTS, and its application to a general case with all the detail required in water resources planning has been published in the fifth article presented in Annex 5, taking the Júcar River Basin as a case study. From these results, a classification of water exploitation systems was carried out according to their degree of stress. These results were compared with the ones in Annex 2 which proposes the use of the indicator of exploitable water resources and which has been obtained with the traditional water balances approach. Finally, Annex 6 includes the last publication of this thesis focused on the effects of climate change in the Po River Basin (Italy) by using water accounting. This work has served to identify those key elements within the simulation models and opens the door to improve them within the approach proposed by the SEEA-W. This thesis aims to collaborate with those responsible for European policies in water resource planning for the application of those methodologies and tools appropriate to each territory. / [ES] Las nuevas políticas europeas establecidas en el Blueprint (EC, 2012) proponen el uso de la contabilidad del agua para la asignación y reserva de los recursos. Esta corrección del rumbo (cambio de paradigma) contrasta con el cálculo de balances que se ha venido utilizando desde el siglo pasado en España para dicho fin. Según la Comisión Europea (EC, 2015) la diferencia entre ambos planteamientos se halla en la inclusión de la componente económica. Este argumento es indiscutible, pero habría que añadir además que tanto las "asset accounts" como las tablas físicas de uso y suministro requieren un tipo de información que hasta ahora no se había considerado. A la vista de este nuevo reto, el uso de los modelos hidrológicos y de gestión de los recursos hídricos se hace imprescindible. Con esta tesis se pretende llevar a cabo una metodología que permita la transición entre los balances hídricos y las cuentas del agua teniendo en cuenta las especiales características de las cuencas mediterráneas (con un elevado grado de regulación y el uso de recursos no convencionales). En esta misma línea se plantea la definición de un indicador que trate de discutir el comportamiento conjunto de un sistema de recursos hídricos y que tenga en consideración el origen de los recursos empleados como medida del grado de estrés de los sistemas. Esta tesis se presenta por compendio de publicaciones y trata de abordar las metodologías e indicadores utilizados hasta la fecha en la planificación y gestión de los recursos hídricos. En primer lugar se analiza el estado del arte que constituye la primera publicación de la tesis, tal y como se detalla en el Anexo 1. La segunda publicación, analiza los elementos clave para la formulación de balances que determinarán, en gran medida, los resultados obtenidos, tal y como se detalla en el Anexo 2. La tercera publicación, en el Anexo 3, trata de explicar cómo en las cuencas donde el aprovechamiento de los recursos es cercano o incluso superior a su disponibilidad, el uso de los balances basados únicamente en variables como la precipitación y la temperatura no son suficientes, sino que debido a la alta regulación de los recursos debe recurrirse además a los modelos de gestión. Este planteamiento contrasta con las propuestas planteadas por los países del norte de Europa centrados principalmente en los modelos hidrológicos. Para abordar el tema se ha partido de un caso piloto localizado en las cuencas mediterráneas andaluzas. Este trabajo se presenta en la cuarta publicación, que se reproduce en el Anexo 4. A partir de este análisis inicial, se vio la necesidad de desarrollar un software complementario que permitiese unificar tanto la información de partida como los resultados de los modelos hidrológicos y de gestión para el cálculo de la contabilidad del agua. El desarrollo de este software, que ha sido denominado AQUACCOUNTS, y su aplicación a un caso general con todo el detalle requerido en planificación se ha publicado en el quinto artículo que se presenta en el Anexo 5, siendo la Demarcación Hidrográfica del Júcar el caso de estudio. A partir de los resultados obtenidos se ha llevado a cabo una clasificación de los sistemas de explotación según su grado de desarrollo comparándose con los resultados obtenidos en el Anexo 2 que propone el uso del indicador de recursos explotables y que se ha obtenido con las metodologías tradicionales de balances. Por último, el Anexo 6 recoge la última publicación de esta tesis en la que se analizan los efectos del cambio climático en la cuenca del río Po (Italia) mediante el uso de la contabilidad del agua. Este trabajo ha servido para identificar aquellos elementos clave dentro de los modelos de simulación y abre las puertas a una mejora de los mismos dentro del enfoque planteado por el SEEA-W. Esta tesis pretende colaborar con los responsables de las políticas europeas en materia de planificación para la apl / [CA] Les noves polítiques europees establides en el Blueprint (EC, 2012) proposen l'ús de la comptabilitat de l'aigua per a l'assignació i reserva dels recursos hídrics. Esta correcció del rumb (o canvi de paradigma) contrasta amb el càlcul de balanços que s'ha utilitzat des del segle passat a Espanya per a aquesta finalitat. Segons la Comissió Europea (EC, 2015) la diferència entre ambdós plantejaments es troba en la inclusió de la component econòmica. Este argument és indiscutible, però caldria afegir a més que tant les "asset accounts" com les taules físiques d'ús i subministrament requerixen un tipus d'informació que fins ara no s'havia considerat. A la vista d'este nou repte, l'ús dels models hidrològics i de gestió dels recursos hídrics es fa imprescindible. Amb esta tesi es pretén dur a terme una metodologia que permeta la transició entre els balanços hídrics i els comptes de l'aigua tenint en compte les especials característiques de les conques mediterrànies (amb un elevat grau de regulació i l'ús de recursos no convencionals). En esta mateixa línia es planteja la definició d'un indicador que tracte de discutir el comportament conjunt d'un sistema de recursos hídrics i que tinga en consideració l'origen dels recursos empleats com a mesura del grau d'estrés dels sistemes. Esta tesi es presenta per compendi de publicacions i tracta d'abordar les metodologies i indicadors utilitzats fins a la data en la planificació i gestió dels recursos hídrics. En primer lloc s'analitza l'estat de l'art que constituïx la primera publicació de la tesi, tal com es detalla en l'Annex 1. La segona publicació, analitza els elements clau per a la formulació de balanços que determinaran, en gran manera, els resultats obtinguts, tal com es detalla en l'Annex 2. La tercera publicació, en l'Annex 3, tracta d'explicar com en les conques on l'aprofitament dels recursos és pròxim o inclús superior a la seua disponibilitat, l'ús dels balanços basats únicament en variables com la precipitació i la temperatura no són suficients, sinó que a causa de l'alta regulació dels recursos ha de recórrer-se a més als models de gestió. Este plantejament contrasta amb les propostes plantejades pels països del nord d'Europa centrats principalment en el models hidrològics. Per a abordar el tema s'ha partit d'un cas pilot localitzat en les conques mediterrànies andaluses. Este treball es presenta en la quarta publicació, que es reproduïx en l'Annex 4. A partir d'aquest anàlisi inicial, es va veure la necessitat de desenrotllar una ferramenta complementaria que permetera unificar tant la informació de partida com els resultats dels models hidrològics i de gestió per al càlcul de la comptabilitat de l'aigua. El desenrotllament d'esta ferramenta, que ha sigut denominat AQUACCOUNTS, i la seua aplicació a un cas general amb tot el detall requerit en planificació s'ha publicat en el quint article que es presenta en l'Annex 5, sent la Demarcació Hidrogràfica del Xúquer el cas d'estudi. A partir dels resultats obtinguts s'ha dut a terme una classificació dels sistemes d'explotació segons el seu grau de desenrotllament comparant-se amb els resultats obtinguts en l'Annex 2 que proposa l'ús de l'indicador de recursos explotables i que s'ha obtingut amb les metodologies tradicionals de balanços. Finalment, l'Annex 6 arreplega l'última publicació d'esta tesi en què s'analitzen els efectes del canvi climàtic en la conca del riu Po (Itàlia) per mitjà de l'ús de la comptabilitat de l'aigua. Este treball ha servit per a identificar aquells elements clau dins dels models de simulació i obri les portes a una millora dels mateixos dins de l'enfocament plantejat pel SEEA-W. Esta tesi pretén col·laborar amb els responsables de les polítiques europees en matèria de planificació per a l'aplicació d'aquelles metodologies i ferramentes més adequades a cada territori. / Pedro Monzonís, M. (2016). Assessment of water exploitation indexes based on water accounting [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/71677 / Compendio

The objective of this thesis is evaluation of financial health of Pilkington Czech s.r.o. by using chosen methods of financial analysis. It contains concepts of potential solutions of discovered problems, which have to lead in the future to the improvements of financial situation of the company.

published_or_final_version / Environmental Management / Master / Master of Science in Environmental Management

本研究探討費率自由化政策與台灣產物保險市場經營效益，利用實證資料評估產物保險公司之整體經營績效及核保利潤。本研究自保險年鑑、台灣經濟新報資料庫及保險市場重要指標，選取1998年至2006年間財務及業務資訊來進行實證分析。 依Klein (1999)分類，台灣產物保險市場屬於類似獨占性競爭市場，產物保險公司高度競爭。依實證結果顯示，實施費率自由化政策，公司自留費用率持續緩慢增加，自留綜合成本率亦呈現上升趨勢。多數產物保險公司之實際核保利潤仍大於依Fairley (1979)計算之均衡核保利潤。 實證結果摘要如下： (1) 類似獨占性競爭市場：赫芬多指數皆小於0.1，市場呈現競爭狀態。1996年後，火險及車險之簽單保費成長率似乎每四、五年會呈現負成長。另外，1998-2003年費用率與公司規模呈現顯著負相關(p=0.01)。2004-2006年，此負相關並不顯著(p=0.1)，顯示大公司漸不具有成本優勢，即產險市場之進入障礙有減少之趨勢。 (2) 成本費用支出增加：除2001年外，1998至2006年之產物保險公司自留綜合成本率介於91.09% 和 93.49%。2006年之自留綜合成本率為93.49%。2006年之產物保險公司費用率上升至40.51% 且損失率下降至52.97%。 (3) 核保利潤呈現正值：依Fairley(1979)計算之2006年預期均衡核保利潤。20家產物保險公司，17家實際核保利潤大於預期均衡核保利潤。 / This paper provides an empirical study of rate deregulation plan and profit performance in Taiwan property-liability insurance market. The data used in this study are from Insurance Year Book, Taiwan Economic Journal Data Bank, and Important Indexes of Insurance Industry (Taiwan) during the period from 1998 to 2006. Based on the classification by Klein (1999), the market structure of Taiwan property-liability insurance industry is similar to monopolistic competitive market and the property-liability insurers are engaged in intense competition. The results of this study show that the expense ratios of insurers rise slightly from year to year and the combined ratios also follow a trend of increase. The actual underwriting profits of most property-liability insurers are larger than the expected numbers estimated by using the methodology in Fairley (1979). The empirical results are as follows: (1) The market structure is similar to monopolistic competitive market for that the Herfindahl indexes are all below 0.1. The growth ratios of written premium on fire insurance and automobile insurance seem to become negative every four or five years after 1996. Besides, the negative correlation between expense ratio and the scale of economics in insurance market from 1998 to 2003 was significant at the p = 0.01 level. However, this correlation from 2004 to 2006 was not significant at the p = 0.1 level. It seems that larger insurers do not have significant cost advantages over smaller insurers in the recent years, namely the entry barriers decline. (2) The expenses and costs keep increasing. Except 2001, the combined ratios ranged from 91.09% in 1998 to 93.49% in 2006. The expense ratio increased to 40.51% while the net loss ratio decreased to 52.97% in 2006. (3) The underwriting profits of most insurers are positive. The expected underwriting profits by using the methodology in Fairley (1979) is less than the actual ones in 2006. Among the 20 property-liability insurers, the actual underwriting profits of 17 insurers were larger than their expected underwriting profits.

<p>Cilj: Proveriti da li je moguće promeniti način CT verifikacije Hallerovog indeksa u okviru preoperativne pripreme pacijenata sa deformitetom grudnog ko&scaron;a po tipu pectus excavatum-a, uz utvrđivanje fiziolo&scaron;kog opsega vrednosti indeksa, njegove zavisnosti od uzrasta i pola, kao i respiratorne faze u kojoj se CT pregled izvodi. Utvrditi značaj vrednosti indeksa korekcije, indeksa asimetrije i indeksa torzije sternuma. Proveriti i mogućnost smanjivanja efektivne doze jonizujućeg zračenja kod primene CT tehnike jednog skena (single slice). Materijal i metod rada: Ispitivanje se sastojalo iz prospektivne studije koja je obuhvatila 30 pacijenata sa pektus ekskavatumom uz CT snimanje (single slice) u respiratornim fazama: ekspirijum i inspirijum. Na dobijenim snimcima su izračunati pored Halerovog indeksa i indeksi asimetrije, korekcije i sternalne torzije. Prema dobijenim rezultatima merenja i izračunavanja, dono&scaron;ena je odluka o načinu terapijskog tretmana. U retrospektivnoj studiji, urađena je analiza 100 CT pregleda grudnog ko&scaron;a kod dece gde nije verifikovan pectus excavatum, uz kalibriranje vrednosti indeksa u odnosu na uzrast i pol pacijenata. Retrospektivno istraživanje je obuhvatilo i analizu dodatnih 30 CT pregleda grudnog ko&scaron;a pacijenata sa deformitetom grudnog ko&scaron;a po tipu pectus excavatum-a, koji su dijagnostikovani i/ili operisani. Kod svih operisanih pacijenata je primenjenja Nusova operativna tehnika. U ovoj grupi pacijenata je izračunata srednja vrednost efektivne doze jonizujućeg zračenja, a dobijene vrednosti su potom komparirane sa efektivnim dozama koje su dobijene niskodoznim CT pregledima grudnog ko&scaron;a uz primenu novog protokola (&quot;single-slice&quot; tehnika u respiratornim fazama inspirijuma i ekspirijuma). Rezultati: Fiziolo&scaron;ki opseg vrednosti Haller-ovog indeksa u populaciji zdravih pacijenata se kretao od 1,47 do 3,17 i u proseku je iznosio 2,23&plusmn;0,32 (znatna pozitivna korelacija uzrasta i vrednosti HI). Na osnovu rezultata Man-Vitnijevog testa nije postojala polna razlika u posmatranoj grupi. Haller-ov indeks u grupi dijagnostikovane/operisane dece je u proseku iznosio 3,39 i kretao se u intervalu od 2,23 do 5,72 (korelacija između uzrasta ovih pacijenata i Haller-ovog indeksa je bila neznatna i negativna). Utvrđena je zavisnost veličine Haller-ovog indeksa od respiratorne faze u kojoj se CT pregled izvodi. Tako su prosečne vrednosti Haller-ovog indeksa u inspirijumu dece sa dijagnostikovanim deformitetom iznosile 2,69&plusmn;0,76. Kod dece ove grupe u ekspirijumu vrednosti Haller-ovog indeksa su iznosile 3,49&plusmn;1,19. U inspirijumu su samo 3/32 (9%) ispitanika imali vrednost HI preko 3,25 (granična vrednost za operativni tretman), dok ih je u ekspirijumu bilo znatno vi&scaron;e 13/32 (41%), &scaron;to je statistički značajna razlika (&chi;2=6,250; df =1; p=0,012). &quot;Single-slice&quot; tehnika CT pregleda u inspirijumu i ekspirijumu 20-25 puta smanjuje efektivnu dozu jonizujućeg zračenja. Zaključak: Vrednost Haller-ovog indeksa raste sa uzrastom deteta, dok nije utvrđena zavisnost Haller-ovog indeksa od pola. Moguće je promeniti načini CT verifikacije Haller-ovog indeksa u preoperativnoj pripremi za Nuss-ovu operaciju primenom &quot;single-slice&quot; tehnike u ekspiratornoj fazi. Osim Hallerovog indeksa, korisno je određivati i indeks korekcije, indeks asimetrije i indeks sternalne rotacije. Predlaže se protokol standardne preoperativne pripreme i lečenja pacijenata dečjeg uzrasta sa deformitetom grudnog ko&scaron;a po tipu pektus ekskavatuma, sa ciljem njegove primene u svakodnevnom radu u institucijama koje se bave ovim problemom, a u cilju pobolj&scaron;anja kvaliteta dijagnostikovanja i krajnjeg ishoda lečenja.</p> / <p>Aim: The aim of this study was to verify whether it is possible to change the way of CT verification of Haller index (HI), as part of preoperative preparation for patients with pectus excavatum, with the determination of the physiological range of the index value, its dependence on the age and sex, as well as the respiratory phase during which the scan is performed. Also, the aim was to determine the significance of correction, asymmetry and sternal torsion indices values. Evaluate the possibility of reduction the effective dose of ionizing radiation using a single slice CT scan technique. Materials and methods: The study consisted of prospective study that included evaluation of CT scans (single slice technique) of 30 patients with pectus excavatum in both respiratory phases: expirium and inspirium. Haller index and indices of asymmetry, correction and sternal torsion were measured. The decision for the treatment was made according to the results of measurements and calculations of these indices. In retrospective study, 100 CT scans of the chest in children without the deformity (pectus excavatum) were analyzed, and the index value was calibrated depending on the age and gender. The retrospective study also included the analysis of another 30 CT scans in patients who were operated or diagnosed with pectus excavatum. Nuss procedure was used in all operated patients. In this group of patients the median value of effective dose of ionizing radiation was calculated, and the values were compared with the effective dose obtained using low-dose CT examinations applied in the new protocol (single-slice technique in inspiratory and expiratory respiratory phases). Results: The physiological range of Haller index value in healthy patients was from 1.47 to 3.17 and average value was 2.23&plusmn;0.32 (significant positive correlation between age and the value of HI). Results of Mann- Whitney test did not demonstrate any difference between gender in the observed group. In the group of patients who were operated/diagnosed with pectus excavatum the average value of Haller index was 3.39 within the range of 2.23 to 5.72 (correlation between the age of these patients and Haller index was negative, but not significant). The dependence of the Haller index value and certain respiratory phase during which the CT scan was performed also was determined. Thus, the average value of Haller index in inspirium in children with diagnosed deformity was up to 2.69&plusmn;0.76. In the same group of patients the value of Haller index in expirium was up to 3.49&plusmn;1.19. Only 3/32 (9%) patients had HI value over 3.25 (a boundary value for surgical treatment) during inspirium, while 13/32 (41%) patients had it in expirium, this data showed statistically significant difference (&chi;2=6.250; df=1; p=0.012). Single-slice CT technique during the inspiratory and expiratory phase reduces 20-25 times the effective dose of ionizing radiation. Conclusion: The value of Haller index increases with the age, but its dependence on the gender was not determined. It is possible to change the way of CT verification of Haller index in preoperative preparation for the Nuss operation using the &quot;single-slice&quot; technique in exspiratory phase. In addition to Haller index it is useful to determine correction index, the index of asymmetry and the index of sternal rotation as well. This protocol is proposed for standard preoperative preparation and treatment of pediatric population with pectus excavatum with the aim of its application in daily work in institutions that deal with this problem, but also to improve the quality of diagnosis and treatment outcomes.</p>

Few studies have examined the impact of portfolio concentration upon the realised volatility of stock index portfolios, such as the FTSE 100. Instead, previous research has focused upon diversification across industries, across geographic regions and across different firms. The present study addresses this imbalance by calculating the daily time series of four concentration metrics for the FTSE 100 Index over the period from January 1984 through March 2003. In addition, the value weighted variance covariance matrix (VCM) of daily FTSE 100 Index constituent returns is decomposed into four sub-components: two from the diagonal elements and two from the off-diagonal elements of the VCM. These consist of the average variance of constituent returns, represented by the sum of diagonal elements in the VCM, and the average covariance represented by the sum of off-diagonal elements in the VCM. The value weighted average variance (VAV) and covariance (VAC) are each subdivided into the equally weighted average variance (EAV) the equally weighted average covariance (EAC) and incremental components that represent the difference between the respective value-weighted and equally weighted averages. These are referred to as the incremental average variance (IAV) and the incremental average covariance (IAC) respectively. The incremental average variance and the incremental average covariance are then combined, additively, to produce the incremental realised variance (IRV) of the FTSE 100 Index. The incremental average covariance and the incremental realised variance are found to be negative during the 1987 crash and the 1992 ERM crisis. They are also negative for a substantial part of the study period, even when concentration was at its highest level. Hence the findings of the study are consistent with the notion that the value weighted, and hence concentrated, FTSE 100 Index portfolio is generally less risky than a hypothetical equally weighted portfolio of FTSE 100 Index constituents. Furthermore, increases in concentration tend to precede decreases in incremental realised volatility and increases in the equally weighted components of the realised VCM. The results have important implications for portfolio managers concerned with the effect of changing portfolio weights upon portfolio volatility. They are also relevant to passive investors concerned about the effects of increased concentration upon their benchmark indices, and to providers of stock market indices.

Cette thèse étudie la trajectoire historique des enquêtes psychologiques produites au Survey Research Center de l’Université du Michigan à l’initiative de George Katona. Aujourd’hui, on ne retient de ces enquêtes que les indicateurs de confiance produits chaque mois par plus de cinquante pays pour analyser la conjoncture. Pourquoi continue-t-on à produire et à utiliser ces enquêtes et ces indicateurs alors qu’un consensus s’est produit en macroéconomie et en microéconomie autour d’un ensemble de modèles qui n’en font pas l’usage ? Pour répondre à cette question, on étudie plusieurs controverses qui se sont produites autour des enquêtes du Michigan entre 1944 et 1960. On montre que l’époque est caractérisée de décisions au sein des gouvernements et du monde des affaires. La thèse montre que si ces débats sont peu connus des économistes aujourd’hui, c’est parce qu’ils se sont poursuivis dans des champs disciplinaires périphériques à l’économie. Ces disciplines sont concernées par des problèmes pratiques dont les économistes théoriciens se sont progressivement détournés. En proposant une analyse des liens entre la théorie économique et sa mise en pratique, cette thèse offre une nouvelle manière d’appréhender l’histoire de la macroéconomie récente et de l’économie comportementale. L’histoire des dynamiques intellectuelles d’après-guerre ne se résume ni à des innovations théoriques, ni à un nouveau rapport entre la théorie et l’empirie. En effet, ces dynamiques reposent aussi sur la redéfinition des frontières entre la science et son art ; entre d’un côté l’économie et de l’autre le marketing et la conjoncture. / This dissertation looks at the historical development of George Kantona's psychological surveys at the Survey Research Center at the University of Michigan. The main legacy of this work has been the widespread adoption of confidence indicators. They are used each month by more than fifty countries and widely implemented by business managers and forecasters. How do we explain the widespread usage of these indicators despite a prevalent consensus in macroeconomics and microeconomics that does not consider them as important tools? In order to answer this question, we study several controversies that occurred around Michigan surveys between 1944 and 1960. It is shown that this era is characterized by many interdisciplinary exchanges guided by the practical needs of decision-makers in governments and private companies. I show that if economists know little about these debates, it is because they were maintained in disciplinary fields on the periphery of economics. These fields are centered on practical problems that theoretical economists progressively abandoned. This thesis offers a new way of understanding the history of recent macroeconomics and behavioral economics by proposing an analysis of the links between economic theory and its application in practice. For instance, the history of post-war intellectual dynamics cannot be reduced to theoretical innovations or to a new relationship between theory and empiricism. Indeed, these dynamics rely also on the transformation of the boundaries between the science and its art; between the economy on the one hand and marketing and forecasting on the other.

O uso de ferramentas estatísticas no ciclo de vida de um produto farmacêutico permite verificar e controlar o processo tendo como objetivo a sua melhoria contínua. No presente estudo foi avaliada a estabilidade e a capacidade estatística do processo de fabricação dos comprimidos revestidos de lamivudina 3TC e zidovudina AZT (150 + 300 mg) fabricados pela Fundação para o Remédio Popular \"Chopin Tavares de Lima\" (FURP). Esse medicamento, distribuido gratuitamente pelo programa DST/AIDS do Ministério da Saúde, e fabricado por compressão direta, processo rápido que permite a implementação futura da tecnologia analítica de processo (Process Analytical Technology - PAT). No Capítulo I foi realizada avaliação retrospectiva da variabilidade de atributos criticos da qualidade de 529 lotes dos comprimidos fabricados de acordo com a RDC ANVISA 17/2010 e as monografias oficiais, sendo tais atributos: peso médio, uniformidade de dose unitária e % m/v de fármaco dissolvido, antes e após o revestimento. O objetivo foi identificar eventuais causas especiais de variabilidade dos processos que permitam melhorias contínuas. No Capitulo II foi desenvolvida metodologia analítica empregando a espectroscopia no infravermelho próximo com transformada de Fourier para a avaliação da homogeneidade da mistura dos pós. Nesse estudo foram analisadas amostras de misturas dos fármacos lamivudina 3TC e zidovudina AZT e mistura excipiente, empregando como método de referência a CLAE, para a quantificação desses dois fármacos. No Capitulo I, a avaliação do processo para o peso médio revelou a necessidade de investigação das causa especiais de variabilidade, evidenciada por meio das cartas de controle. Os resultados do ano de 2015 indicaram necessidade de centralização e de consistência do processo, com redução de probabilidade de falha. As cartas de controle para uniformidade de dose unitária, no ano de 2013, revelaram menor variabilidade do processo. Porem, nesse ano, a análise estatística para a dissolução revelou processo descentralizado e sem consistência, com maior evidência para o fármaco 3TC que demonstrou menor desempenho, Cpk<1,0. A avaliação da estabilidade e da capacidade do processo de fabricação de comprimidos de lamivudina + zidovudina (150+300 mg), no período de 2012 a 2015, permitiu o maior entendimento de suas fontes de variação. Foi possível detectar e determinar o grau dessa variação e seu impacto no processo e nos atributos críticos de qualidade do produto com evidentes oportunidades de melhoria do processo, reduzindo os riscos para o paciente. No capítulo II, no desenvolvimento do método, as estatísticas de validação revelaram que os menores valores de BIAS foram observados para a 3TC, 0,000116 e 0,0021, respectivamente para validação cruzada e validação. Os valores de BIAS próximos a zero indicaram reduzida porcentagem de variabilidade do método. O presente estudo demonstrou a viabilidade do uso do modelo desenvolvido para a quantificação da 3TC e AZT por FT-NIR apos ajustes que contribuam para a elevação de R, R2 e RPD para valores aceitáveis. Valores de RPD acima de 5,0 que permitem o uso do modelo para uso em controle de qualidade. / The use of statistical tools in the life cycle of a pharmaceutical product allows verifying and controlling the process aiming at its continuous improvement. In the present study, the stability and statistical capacity of the lamivudine coated tablets 3TC and zidovudine AZT (150 + 300 mg) manufactured by the Chopin Tavares de Lima Foundation (FURP) were evaluated. This drug, distributed free of charge by the Ministry of Health\'s DST/AIDS program, is manufactured by direct compression, a rapid process that allows the future implementation of Process Analytical Technology (PAT). In Chapter I, a retrospective evaluation of the variability of critical quality attributes of 529 batches of tablets manufactured was carried out, such attributes being: mean weight, unit dose uniformity and % m/v of dissolved drug substances, before and after coating. The objective was to identify possible special causes of variability of the processes that allow continuous improvements. In Chapter II an analytical methodology was developed employing the near infrared spectroscopy with Fourier transform for the evaluation of the homogeneity of the powder mixture. In this study, samples of mixtures of the drugs lamivudine 3TC and zidovudine AZT and excipient mixture were analyzed, using as reference method the HPLC, for the quantification of these two drugs. In Chapter I, the evaluation of the process for the mean weight revealed the need to investigate the special cause of variability, as evidenced by the charts. The results of the year 2015 indicated the need for centralization and process consistency, with a reduction in the probability of failure. The control charts for unit dose uniformity, in the year 2013, revealed less process variability. However, in that year, the statistical analysis for dissolution revealed a decentralized process with no consistency, with greater evidence for the 3TC drug that showed lower performance, Cpk<1.0. The evaluation of the stability and capacity of the lamivudine + zidovudine tablet manufacturing process (150 + 300 mg) in the period from 2012 to 2015 allowed a better understanding of its sources of variation. It was possible to detect and determine the degree of this variation and its impact on the process and the critical quality attributes of the product with evident opportunities to improve the process, reducing risks for the patient. In Chapter II, in the development of the method, the validation revealed that the lowest values of BIAS were observed for 3TC, 0.000116 and 0.0021, respectively for cross validation and validation. BIAS values close to zero indicated a reduced percentage of variability of the method. The present study demonstrated the feasibility of using the model developed for the quantification of 3TC and AZT by FT-NIR after adjustments that contribute to the elevation of R, R2 and RPD to acceptable values. RPD values above 5.0 that allow the use of the model for use in quality control.

Trauma and Injury Severity Score (TRISS) é um índice que permite calcular probabilidade de sobrevida de pacientes traumatizados. Para seu cálculo são necessárias as informações: idade; tipo de trauma - penetrante ou contuso; valor do Revised Trauma Score (RTS); e pontuação do Injury Severity Score (ISS). Em 1997 foi realizada uma revisão do ISS com o intuito de melhorar sua acurácia na determinação da gravidade do trauma. Essa revisão resultou em mudança no cálculo desse índice e, consequentemente, em uma nova versão, o New Injury Severity Score (NISS). Resultados de estudos têm indicado que o NISS se iguala ou supera o ISS na previsão de mortalidade. Procurou-se neste estudo verificar se a substituição do ISS pelo NISS, na fórmula original do TRISS, melhora sua estimação de sobrevida. Trata-se de pesquisa retrospectiva realizada no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. A população foi constituída por 533 pacientes traumatizados atendidos e internados no Pronto-Socorro deste hospital pelo período de um ano. Foi realizada análise descritiva das características das vítimas e calculadas as medidas de posição para as variáveis contínuas. Para verificar qual o melhor indicador (TRISS ou NTRISS) para probabilidade de sobrevida e o melhor ponto de corte, foi utilizada a curva ROC. Os resultados foram confrontados com as mortes e sobrevidas observadas com o intuito de se identificar a fórmula mais acurada para cálculo da probabilidade de sobrevida. Fizeram parte do estudo pacientes traumatizados entre 18 e 95 anos, sendo a maioria jovens (61,9%), do sexo masculino (80,5%). Os acidentes de transporte foram as causas externas mais frequentes (61,9%), e, consequentemente, houve predomínio de trauma contuso (87,1%). Do total de pacientes, 82,9% foram atendidos por unidades sistematizadas de atendimento pré-hospitalar. A região mais freqüentemente traumatizada foi a superfície externa (63,0%), seguida por cabeça e pescoço (55,5%). Os pacientes estiveram internados por uma média de 11,0 dias (+ 18,0). Dos 533 pacientes, 42,2% necessitaram de internação em Unidade de Terapia Intensiva. A taxa de sobrevida foi de 76,9%. A maioria dos indivíduos (54,5%) apresentou valor de RTS de 7 a 7,84. O escore do ISS e do NISS variou de 0 a 75, com predomínio do escore de 9 a 15 (40,0%) para o ISS e de 16 a 24 (25,5%) para o NISS. O valor do TRISS e do NTRISS variou de 0 a 100,0%; probabilidade de sobrevida maior ou igual a 75,0% foi apresentada por 83,4% dos pacientes segundo o TRISS e por 78,4% dos pacientes de acordo com o NTRISS. O TRISS superestimou a probabilidade de sobrevida dos pacientes traumatizados. Houve diferença estatisticamente significativa entre a previsão de sobrevida dada pelo TRISS e NTRISS, e o NTRISS foi mais assertivo que o TRISS para prever sobrevida dos pacientes atendidos neste centro de trauma / The Trauma and Injury Severity Score (TRISS) is an index that permits the calculation of survival probability in trauma victims. The following information is necessary to perform this calculation: age, trauma type -penetrating or contusion; value from the Revised Trauma Score (RTS); and the scores from the Injury Severity Score (ISS). In 1997, a revision was done to the ISS to improve its accuracy for determining the severity of traumas, thus resulting in a new version called the New Injury Severity Score (NISS). Studies have shown that this NISS is equal to or greater than the ISS in the prediction of mortality. The objective of this study was to verify if substituting the ISS with the NISS, in the original TRISS form, improved the survival rate estimate. This retrospective study included 533 trauma victims who were attended and interned in the emergency room during a period of 1 year, in \"Hospital das Clínicas\" of the Medical School of the University of Sao Paulo. A descriptive analysis of the characteristics of the victims was performed and the position measurements for the continuous variables were calculated. An ROC curve was used to verify which would be the best indicator (TRISS or NTRISS) for calculating the survival probability. The results were compared with the deaths and survivors in order to indentify the most accurate formula for calculating survival probability. Included in this study were trauma victims, between the ages of 18 to 95, with the majority being youths (61.9%) and of the male gender (80.5%). Contributing causes were predominantly from motor vehicle accidents (61.9%), and predominantly with contusions (87.1%). Of the total victims, 82.9% were treated in first aid clinics. The most frequent trauma regions were superficial (63%) followed by the head and neck (55.5%) The victims were interned on an average of 11 days. ( +18.0). Of the 533 victims 42.2% were interned in the Intensive Care Unit (ICU) and the survival rate was 76.9%. The majority of individuals (54.5%) had RTS scores between 7 and 7.84. The ISS and NISS score varied from 0 to 75, with the average ISS score ranging from 9-15 (40.0%) and the NISS score from 16-24 (25.5%). The TRISS and NTRISS scores varied between 0 and 100 %; probability of survival equal to or greater than 75.0% was presented for 83.4% of the victims according to TRISS and 78.4% according to NTRISS thus, the TRISS overestimated the probability of survival in trauma victims. There was a statistically significant difference in the estimate of survivability data between the TRISS and NTRISS with the latter being the more accurate scale for predicting survivability among the victims treated in this trauma center

Das Ziel der vorliegenden Arbeit bestand darin, in Modellversuchen in Wasserkultur und im Festsubstrat sowohl elementspezifische (Mg-, Fe-, Mn- oder Zn-Mangel) als auch komplexe N hrstoffmangelsituationen (gleichzeitiger Mangel an Fe, Mn und Zn) zu simulieren und die Wirkung pr ventiver resp. kurativer Blattapplikationen auf Wachstum und Ertrag von Buschbohnenpflanzen zu untersuchen. Zusammengefaát wurden folgende Ergebnisse erzielt. Bei unzureichendem Mg- und Fe-Angebot sowie bei gleichzeitigem Mangel an Fe, Mn und Zn wurden das Wachstum und die Ertragsbildung hochsignifikant vermindert. Die Auswirkungen des Mg-Mangels auf Wachstum und Ertrag wurden durch die pr ventive Blattapplikation erfolgreich ausgeglichen. Die verwendeten Mikron hrstoff-Formulierungen waren bei Fe-Mangel bzw. bei multipler Mikron hrstoff-Unterversorgung, im Gegensatz zu Mn- bzw. Zn-Mangel, weniger wirksam. Aufgrund des N hrstoffmangels w hrend der generativen Phase wurden die gebildeten Bl ten und H lsen abgeworfen. Den Mangelpflanzen erm glichte die Blattapplikation erst die H lsenbildung. Ausschlaggebend f r die H he des H lsenertrages war die Anzahl der gebildeten H lsen, da das H lsengewicht nicht wesentlich beeinfluát wurde. Aufgrund des verminderten N hrstoffangebotes im N hrmedium nahm die Konzentration der betroffenen N hrstoffe im Blatt bis in den kritischen Grenzwertbereich ab. Mit Ausnahme der Fe-Mangelvarianten wirkte die Blattd ngung dieser Abnahme der N hrstoffkonzentration erfolgreich entgegen. Hinsichtlich Wachstum Ertragsbildung und N hrstoffaufnahme wurden, sowohl bei den Mg- als auch bei den Mikron hrstoff-Blattd ngern keine von der Zusammensetzung abh ngigen Wirksamkeitsunterschiede festgestellt. Bez glich der untersuchten Parameter des Wachstums und der Ertragsbildung erwies sich die pr ventive Mg-Blattapplikation der kurativen gegen ber als hochsignifikant berlegen. Derart deutliche Wirksamkeitsunterschiede in Abh ngigkeit vom Applikationszeitpunkt blieben bei den Mikron hrstoff-Blattd ngern aus. Ein Mg- und Mikron hrstoffangebot von 10% im Jugendstadium konnte ein ungest rtes vegetatives Wachstum der Pflanzen gew hrleisten. Eine Mg- bzw. Mikron hrstoff-Unterversorgung der Pflanzen w hrend der generativen Phase bewirkte einen R ckgang des Samenertrages von ber 60% bis 80%. Mit Hilfe der Blattapplikationen w hrend der generativen Phase wurde der Abwurf der reproduktiven Organe hochsignifikant vermindert. Dadurch konnten ber 90% des Samenertrages der Kontrolle erreicht werden. Ungeachtet einer erfolgreichen Impfung mit Rhizobium blieben die Pflanzen ohne N-Startd ngung im Vergleich zu einer Startd ngung mit einer quivalentmenge von 40 kg N/ha bei Wachstum und Ertragsbildung hochsignifikant zur ck. Gemessen am Samenertrag konnten die Auswirkungen des N-Mangels im Jugendstadium durch eine Nachd ngung zu Bl hbeginn nicht mehr ausgeglichen werden. Durch die Kombination Nachd ngung zu Bl hbeginn und Blattapplikation w hrend der Kornf llungsphase wurde die Abscission von reproduktiven Organen signifikant vermindert und die h chste Ertragswirksamkeit erzielt. Unabh ngig von den Behandlungen lag der Rohproteingehalt der Samen bei 20%. Auch die anderen N hrstoffe der Samen lagen im normalen Konzentrationsbereich f r Buschbohne. / The aim of this study was to simulate as well specific (Mg-, Fe-, Mn- and Zn-deficiency) as complex nutrient deficiency situations in model systems using either nutrient solution or solid substrates and to investigate the effect of preventive or curative applications of foliar fertilizers on growth and yield of bean plants. Results may be summarized as follows: Insufficient supply of magnesium and iron or simultaneous deficiency in Fe, Mn and Zn resulted in highly significant reduction of growth and yield of bean plants. Effect of magnesium deficiency on growth and yield could be successfully compensated by preventive foliar fertilization. The applied micronutrient compounds were less successful in the case of iron deficiency or multiple micronutrient deficiency situations as compared to manganese or zinc deficiency. Nutrient deficiency during the generative phase resulted in dropping of flowers and pods. In deficient plants foliar fertilizer application was a precondition for pod formation. Since pod weight was not substantially affected by plant nutrition pod number was the decisive factor for pod yield. As a result of reduced nutrient supply in the substrates leaf concentration of investigated nutrients declined below critical deficiency levels. With exception of the Fe-deficiency variants application of foliar fertilizers successfully compensated for the decrease in leaf nutrient concentrations. The composition of Mg and micronutrient foliar fertilizers did not affect significantly plant growth, yield and nutrient uptake. For the investigated parameters of growth and yield formation preventive foliar application of magnesium fertilizers was significantly more effective as compared to curative application. Such distinctive differences in fertilizer effects with time of application could not be found in micronutrient fertilizers. Mg and micronutrient supply of as low as 10% of optimal supply during juvenile growth phase could guarantee undisturbed vegetative growth. Drastic decrease of magnesium or micronutrient supply during the reproductive phase resulted in a reduction of pod yield up to 60 - 80%. Foliar fertilizer application during the reproductive development significantly reduced dropping of reproductive organs and thus seed yields of more than 90% of control were achieved. Nevertheless after a successful inoculation with Rhizobium plants without a nitrogen start dressing had significantly lower growth and yields than those with a starter fertilization of 40 kg N/ha. With regard to seed yield the effects of nitrogen deficiency during the juvenile phase could not be compensated by late fertilization at the flowering stage. The combination of a late fertilization at the flowering stage and leaf application during pod filling resulted in decreased pod abscission and therefore in highest yields. Independently of treatments the raw protein content of the bean seeds approximated to 20%. Also other nutrients in the seeds were in the adequate range for Phaseolus bean.