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Owing to their non-selective nature, anti-cancer drugs affect both cancerous and non-cancerous cells and present a major health risk to healthcare staff working with them. This project was conducted at Derriford Hospital, Plymouth, to investigate the extent of contamination with anti-cancer drugs on work surfaces and the environmental emissions of these drugs. In the Isolator study, surface contamination arising from the preparation of five anticancer drug infusions (epirubicin, fluorouracil, cisplatin, oxaliplatin and carboplatin) in a pharmaceutical isolator and external surfaces of infusion bags and syringes using a conventional syringe and needle technique was investigated and compared with that obtained using a closed system drug transfer device (Tevadaptor). Wipe samples were taken for a period of one week from pre-defined areas in a pharmaceutical isolator and from the surface of prepared Intra-Venous (IV) infusion bags and pre-filled syringes to obtain baseline data. Gloves and preparation mats used during this period were also collected. Following a one-week operator familiarisation period, the Tevadaptor device was then introduced for cytotoxic preparation and wipe-sampling of surfaces and collection of consumables was continued for a further week (intervention period). The samples obtained were then analysed by HPLC and ICP-MS. The baseline contamination data from Tevadaptor isolator study was undetected to 0.9 ng cm-2 (epirubicin), undetected to 3.58 ng cm-2 (5-FU) and 0.05-0.92 ng cm-2 (Pt) in the wipe samples from the pharmaceutical isolator surfaces; amounts on glove samples were 1100-6100 ng/glove (epirubicin), 300-8100 ng/glove (5-FU) and 1-6 ng/glove (platinum). During the intervention phase isolator surface contamination was not detected in all samples for 5-FU and epirubicin and platinum was detected on the isolator surfaces in the range of 0.002-0.09 ng cm-2. The use of Tevadaptor resulted in a reduction of contamination on external surfaces by a factor of 10 or more for all marker drugs. A ward study investigated the surface contamination in the oncology out-patient department caused by cisplatin, oxaliplatin, carboplatin and gemcitabine. The study compared the effect of using the Tevadaptor to prepare and administer anticancer drugs infusions on ward surface contamination to the current UK standard practice. A questionnaire was also distributed to participating staff members to assess the user-friendliness of Tevadaptor. Wipe samples were taken from pre-defined areas from the oncology out-patients department and gloves used by nursing staff for assembly and administration of the above drugs were also collected. Sample collection followed a similar schedule to the Tevadaptor isolator study. The baseline ward surface contamination ranged from undetected to 4.97 ng cm-2 (gemcitabine) and 3.1 ng cm-2 (platinum). In the case of gloves used by nursing staff the levels of contamination ranged from undetected to 1251 ng/glove (gemcitabine) and 405.4 ng/glove (platinum). The contamination on ward surfaces during the intervention phase ranged from undetected to 3.21 ng cm-2 (gemcitabine) and 2.69 ng cm-2 (platinum) and contamination levels on gloves ranged from undetected to 9252 ng/glove (gemcitabine) and 1319 ng/glove (platinum). During the intervention phase there was a reduction in frequency of contamination, even though the total amount of surface contamination by anticancer drugs did not always decrease in comparison to baseline data, presumably due to unaccounted spillages. A drain study investigated the presence of platinum in hospital wastewater as a measure of contamination caused by the excretion of platinum-based anticancer drugs by patients. Platinum was measured over a three week period in one of the main drains and in the effluent of the oncology ward. The study showed the presence of measurable quantity of platinum which ranged from 0.02 to 140 μg L-1 in the oncology effluent and 0.03 to 100 μg L-1 in the main drain. Data from this study was coupled with published measurements on the removal of the drugs by conventional sewage treatment and then concentration of platinum arising from each drug was predicted in recipient surface waters as a function of water flow rate. Although predicted concentrations were below EMEA guidelines warranting further risk assessment, the presence of potentially carcinogenic, mutagenic and teratogenic substances in surface waters is cause for concern. The results showed that a closed system drug transfer device (CSTD) used in conjunction with an isolator is highly efficient in reducing surface contamination with anti-cancer drugs. However, despite current best practice contamination on ward surfaces remained even after the use of a CSTD. Nursing as well as healthcare staff should be educated of these results and the risks of occupational exposure to low levels of anti-cancer drugs and the use of PPE should be emphasised. Results of the drain study form the basis of preliminary estimates of the likely concentrations of platinum-based drugs in surface waters and their potential environmental impacts.

The objective of this study is to investigate the strategic factors that influence the overall performance of manufacturing organisations in different industries. Strategic groups were identified using cluster analysis and their overall performance was evaluated. Structural equation modelling was used to verify the existence of significant linkages between competitive factors and firms' overall performance within the identified strategic groups. The results of this study pointed out to the existence of a relationship between strategic group membership and firm's overall performance. Overall, the results tend to emphasise the importance of viewing manufacturing performance from a system-wide perspective.

A pré-fabricação na arquitetura ainda costuma ser associada à monotonia, repetição, rigidez, e, sobretudo, impossibilidade de participação dos usuários na concepção do produto. Em contraponto a essas associações, dentro de um contexto de expansão global dos sistemas industrializados destinados à construção civil, esse trabalho se propõe a investigar distintas maneiras de aplicar métodos pré-fabricados ao projeto arquitetônico. Faz-se aqui uma análise de três diferentes lógicas de seriação e 5 exibilização utilizadas na produção industrial: o Sistema Fechado, o Sistema Aberto e o Sistema Flexibilizado, buscando-se identi6 car as formas de cada um relacionar-se com o exercício de projeto e em que resultam ou poderiam resultar as diferentes lógicas de seriação e individualização. Objetivando-se identi6 car os fatores que conferem identidade aos projetos face ao emprego de métodos construtivos pré-fabricados, adotou-se, para estudos de caso, a arquitetura de moradia. Tipologia essa que apresenta as relações de maior con5 ito entre individualização e produção seriada. / Prefabrication in architecture is still associated to boredom, repetition, in5 exibility and, mainly, to an impossibility of having users’ participation in the product design. As a counterweight to these associations, within a context of global development of industrialized systems in urban construction, this dissertation proposes an investigation of different ways to apply prefabricated methods to architectural project. Here I do an analysis of three different approaches to serialization and 5 exibilization used in the industrial production: the Closed System, the Open System and the Flexibilized System, trying to identify the way in which each system relates to the execution of the project. I also look at possible results of these different approaches to serialization and individualization. Aiming at specifying the elements which grant identity to the project in terms of the employment of prefabricated building methods, we adopted the housing architecture as case study, since this kind of architecture is the one which presents the biggest con5 icting relations between individualization and serialized production.

A pré-fabricação na arquitetura ainda costuma ser associada à monotonia, repetição, rigidez, e, sobretudo, impossibilidade de participação dos usuários na concepção do produto. Em contraponto a essas associações, dentro de um contexto de expansão global dos sistemas industrializados destinados à construção civil, esse trabalho se propõe a investigar distintas maneiras de aplicar métodos pré-fabricados ao projeto arquitetônico. Faz-se aqui uma análise de três diferentes lógicas de seriação e 5 exibilização utilizadas na produção industrial: o Sistema Fechado, o Sistema Aberto e o Sistema Flexibilizado, buscando-se identi6 car as formas de cada um relacionar-se com o exercício de projeto e em que resultam ou poderiam resultar as diferentes lógicas de seriação e individualização. Objetivando-se identi6 car os fatores que conferem identidade aos projetos face ao emprego de métodos construtivos pré-fabricados, adotou-se, para estudos de caso, a arquitetura de moradia. Tipologia essa que apresenta as relações de maior con5 ito entre individualização e produção seriada. / Prefabrication in architecture is still associated to boredom, repetition, in5 exibility and, mainly, to an impossibility of having users’ participation in the product design. As a counterweight to these associations, within a context of global development of industrialized systems in urban construction, this dissertation proposes an investigation of different ways to apply prefabricated methods to architectural project. Here I do an analysis of three different approaches to serialization and 5 exibilization used in the industrial production: the Closed System, the Open System and the Flexibilized System, trying to identify the way in which each system relates to the execution of the project. I also look at possible results of these different approaches to serialization and individualization. Aiming at specifying the elements which grant identity to the project in terms of the employment of prefabricated building methods, we adopted the housing architecture as case study, since this kind of architecture is the one which presents the biggest con5 icting relations between individualization and serialized production.

Introdução: A manipulação de medicamentos antineoplásicos em Serviços de Saúde expõem os profissionais aos riscos químicos desses agentes, assim é fundamental monitorar e prevenir a exposição ocupacional. A utilização de dispositivos de Segurança no preparo de medicamentos tem sido recomendada por diversos órgãos internacionais de boas práticas no manuseio de medicamentos citotóxicos. Objetivo: Comparar, através da técnica de Cromatografia Líquida de Alta Eficiência com detector Ultravioleta (CLAE-UV), as taxas de contaminação de superfícies de trabalho, com a Gencitabina, utilizando Dispositivos de Segurança em Sistema Fechado em relação à técnica de preparo padrão com agulha. Métodos: A coleta de amostras foi realizada na farmácia de manipulação pela técnica de wipe test e posterior extração. As amostras foram analisadas com CLAE-UV, com leitura de detecção de 268 nm. Resultados: De um total de 303 amostras coletadas para análise da Gencitabina, 272 compararam a técnica com dispositivo de sistema fechado com a técnica padrão, apresentando percentuais de contaminação em quase 50% dos frascos coletados em cada técnica. Os resultados encontrados nos frascos, campo de preparo e seringas apresentaram média de quantidade de resíduos inferiores na técnica com dispositivos de segurança. Nos frascos intactos retirados da caixa original de Gencitabina, foram encontrados resíduos em 16,1%. Conclusões: A técnica utilizada foi adequada para identificar a presença de Gencitabina em materiais e Equipamentos de Proteção Individual – EPI na manipulação de medicamentos, demonstrando dessa forma o risco de exposição aos profissionais e a importância da utilização da do sistema fechado para diminuir os aerossóis e quantidades de resíduos eliminados durante a manipulação. / Introduction: Health professionals who handle antineoplastic agents are exposed to several chemical hazards. Therefore, their occupational exposure must be carefully monitored and prevented. The use of closed-system devices in drug preparation has been recommended by several international guidelines for the handling of cytotoxic drugs. Objective: To compare the contamination of work surfaces with gemcitabine following closed-system preparation versus standard needle techniques, using high-performance liquid chromatography-ultraviolet (HPLC-UV). Method: Wipe test samples were collected from a drug handling facility, then extracted and analyzed by HPLC-UV. Readings were taken at 268 nm. Resultados: Of the 303 samples collected, 31 were obtained from intact vials, while 272 were used to compare gemcitabine contamination levels following conventional versus closed-system preparation. Approximately 50% of samples obtained following each procedure tested positive for the contaminant. The amount of contamination on vials, sterile fields and syringes was lower when closed-system devices were used for drug manipulation. A total of 16.1% of the intact vials removed from their original packaging were also contaminated. Conclusion: The method used in the present study was effective in detecting gemcitabine in the devices and individual protective equipment involved in drug manipulation. These findings demonstrate the exposure risk of health professionals who handle these substances, and the importance of closed-system devices in reducing aerosol formation and contamination during handling.

Introdução: A manipulação de medicamentos antineoplásicos em Serviços de Saúde expõem os profissionais aos riscos químicos desses agentes, assim é fundamental monitorar e prevenir a exposição ocupacional. A utilização de dispositivos de Segurança no preparo de medicamentos tem sido recomendada por diversos órgãos internacionais de boas práticas no manuseio de medicamentos citotóxicos. Objetivo: Comparar, através da técnica de Cromatografia Líquida de Alta Eficiência com detector Ultravioleta (CLAE-UV), as taxas de contaminação de superfícies de trabalho, com a Gencitabina, utilizando Dispositivos de Segurança em Sistema Fechado em relação à técnica de preparo padrão com agulha. Métodos: A coleta de amostras foi realizada na farmácia de manipulação pela técnica de wipe test e posterior extração. As amostras foram analisadas com CLAE-UV, com leitura de detecção de 268 nm. Resultados: De um total de 303 amostras coletadas para análise da Gencitabina, 272 compararam a técnica com dispositivo de sistema fechado com a técnica padrão, apresentando percentuais de contaminação em quase 50% dos frascos coletados em cada técnica. Os resultados encontrados nos frascos, campo de preparo e seringas apresentaram média de quantidade de resíduos inferiores na técnica com dispositivos de segurança. Nos frascos intactos retirados da caixa original de Gencitabina, foram encontrados resíduos em 16,1%. Conclusões: A técnica utilizada foi adequada para identificar a presença de Gencitabina em materiais e Equipamentos de Proteção Individual – EPI na manipulação de medicamentos, demonstrando dessa forma o risco de exposição aos profissionais e a importância da utilização da do sistema fechado para diminuir os aerossóis e quantidades de resíduos eliminados durante a manipulação. / Introduction: Health professionals who handle antineoplastic agents are exposed to several chemical hazards. Therefore, their occupational exposure must be carefully monitored and prevented. The use of closed-system devices in drug preparation has been recommended by several international guidelines for the handling of cytotoxic drugs. Objective: To compare the contamination of work surfaces with gemcitabine following closed-system preparation versus standard needle techniques, using high-performance liquid chromatography-ultraviolet (HPLC-UV). Method: Wipe test samples were collected from a drug handling facility, then extracted and analyzed by HPLC-UV. Readings were taken at 268 nm. Resultados: Of the 303 samples collected, 31 were obtained from intact vials, while 272 were used to compare gemcitabine contamination levels following conventional versus closed-system preparation. Approximately 50% of samples obtained following each procedure tested positive for the contaminant. The amount of contamination on vials, sterile fields and syringes was lower when closed-system devices were used for drug manipulation. A total of 16.1% of the intact vials removed from their original packaging were also contaminated. Conclusion: The method used in the present study was effective in detecting gemcitabine in the devices and individual protective equipment involved in drug manipulation. These findings demonstrate the exposure risk of health professionals who handle these substances, and the importance of closed-system devices in reducing aerosol formation and contamination during handling.

Introdução: A manipulação de medicamentos antineoplásicos em Serviços de Saúde expõem os profissionais aos riscos químicos desses agentes, assim é fundamental monitorar e prevenir a exposição ocupacional. A utilização de dispositivos de Segurança no preparo de medicamentos tem sido recomendada por diversos órgãos internacionais de boas práticas no manuseio de medicamentos citotóxicos. Objetivo: Comparar, através da técnica de Cromatografia Líquida de Alta Eficiência com detector Ultravioleta (CLAE-UV), as taxas de contaminação de superfícies de trabalho, com a Gencitabina, utilizando Dispositivos de Segurança em Sistema Fechado em relação à técnica de preparo padrão com agulha. Métodos: A coleta de amostras foi realizada na farmácia de manipulação pela técnica de wipe test e posterior extração. As amostras foram analisadas com CLAE-UV, com leitura de detecção de 268 nm. Resultados: De um total de 303 amostras coletadas para análise da Gencitabina, 272 compararam a técnica com dispositivo de sistema fechado com a técnica padrão, apresentando percentuais de contaminação em quase 50% dos frascos coletados em cada técnica. Os resultados encontrados nos frascos, campo de preparo e seringas apresentaram média de quantidade de resíduos inferiores na técnica com dispositivos de segurança. Nos frascos intactos retirados da caixa original de Gencitabina, foram encontrados resíduos em 16,1%. Conclusões: A técnica utilizada foi adequada para identificar a presença de Gencitabina em materiais e Equipamentos de Proteção Individual – EPI na manipulação de medicamentos, demonstrando dessa forma o risco de exposição aos profissionais e a importância da utilização da do sistema fechado para diminuir os aerossóis e quantidades de resíduos eliminados durante a manipulação. / Introduction: Health professionals who handle antineoplastic agents are exposed to several chemical hazards. Therefore, their occupational exposure must be carefully monitored and prevented. The use of closed-system devices in drug preparation has been recommended by several international guidelines for the handling of cytotoxic drugs. Objective: To compare the contamination of work surfaces with gemcitabine following closed-system preparation versus standard needle techniques, using high-performance liquid chromatography-ultraviolet (HPLC-UV). Method: Wipe test samples were collected from a drug handling facility, then extracted and analyzed by HPLC-UV. Readings were taken at 268 nm. Resultados: Of the 303 samples collected, 31 were obtained from intact vials, while 272 were used to compare gemcitabine contamination levels following conventional versus closed-system preparation. Approximately 50% of samples obtained following each procedure tested positive for the contaminant. The amount of contamination on vials, sterile fields and syringes was lower when closed-system devices were used for drug manipulation. A total of 16.1% of the intact vials removed from their original packaging were also contaminated. Conclusion: The method used in the present study was effective in detecting gemcitabine in the devices and individual protective equipment involved in drug manipulation. These findings demonstrate the exposure risk of health professionals who handle these substances, and the importance of closed-system devices in reducing aerosol formation and contamination during handling.

A pré-fabricação na arquitetura ainda costuma ser associada à monotonia, repetição, rigidez, e, sobretudo, impossibilidade de participação dos usuários na concepção do produto. Em contraponto a essas associações, dentro de um contexto de expansão global dos sistemas industrializados destinados à construção civil, esse trabalho se propõe a investigar distintas maneiras de aplicar métodos pré-fabricados ao projeto arquitetônico. Faz-se aqui uma análise de três diferentes lógicas de seriação e 5 exibilização utilizadas na produção industrial: o Sistema Fechado, o Sistema Aberto e o Sistema Flexibilizado, buscando-se identi6 car as formas de cada um relacionar-se com o exercício de projeto e em que resultam ou poderiam resultar as diferentes lógicas de seriação e individualização. Objetivando-se identi6 car os fatores que conferem identidade aos projetos face ao emprego de métodos construtivos pré-fabricados, adotou-se, para estudos de caso, a arquitetura de moradia. Tipologia essa que apresenta as relações de maior con5 ito entre individualização e produção seriada. / Prefabrication in architecture is still associated to boredom, repetition, in5 exibility and, mainly, to an impossibility of having users’ participation in the product design. As a counterweight to these associations, within a context of global development of industrialized systems in urban construction, this dissertation proposes an investigation of different ways to apply prefabricated methods to architectural project. Here I do an analysis of three different approaches to serialization and 5 exibilization used in the industrial production: the Closed System, the Open System and the Flexibilized System, trying to identify the way in which each system relates to the execution of the project. I also look at possible results of these different approaches to serialization and individualization. Aiming at specifying the elements which grant identity to the project in terms of the employment of prefabricated building methods, we adopted the housing architecture as case study, since this kind of architecture is the one which presents the biggest con5 icting relations between individualization and serialized production.

Freshwater lakes constrain its methane (CH4) emissions through CH4 oxidation. CH4 includes three carbon (C) isotopes; the stable isotopes 12C,13C and the unstable and more uncommon isotope 14C. Methanotrophs (i.e. methane oxidizing bacteria) oxidize the lighter isotope more rapidly. Changes in relative isotopic composition can therefore be used to calculate how much CH4 is oxidized in a system. This study investigates an annual CH4 oxidation in a freshwater lake. Water samples and bubbles of CH4 gas were collected once a month, from March to November, in lake Gundlebosjön. The CH4 gas was separated from the water samples with a headspace extraction technique. The concentration and isotopic composition of CH4 was analyzed in a cavity ring down spectrometer. The isotopic data was used in two mathematical models, based on open-steady state and closed systems. It was found that the stable isotope method to estimate CH4 oxidation was only useful during periods when clear concentration and isotope differences could be observed in the water column. CH4 oxidation could only be estimated in the water column in August, and in the surface layer in June and July. / Utsläppen av metan (CH4) från sötvattensjöar begränsas genom CH4 oxidation. Det är två stabila kolisotoper som dominerar i CH4; 12C och 13C. Den ostabila kolisotopen 14C finns även i CH4, men den är mer ovanlig i naturen. Metantrofer (metanoxiderande bakterier) oxiderar den lättare kolisotopen snabbare. Förändringar i isotopsammansättningen kan användas för att beräkna hur mycket CH4 som oxideras i ett system. Denna studie undersöker en årlig CH4 oxidation i en sötvattensjö. Vattenprover och bubblor av CH4-gas samlades en gång i månaden, från mars till november, i Gundlebosjön. CH4 gasen separerades från vattenproverna med en ”headspace extraction” teknik. Koncentration och isotopsammansättningen av CH4 analyserades i en ”cavity ring down spectrometer”. Isotopdata användes i två matematiska modeller, baserade på öppet-stabilt tillstånd och stängt system. Den stabila isotopmetoden för att uppskatta CH4 oxidation var endast användbar under perioder då tydliga skillnader i koncentrationen och isotopsammansättningen kunde observeras i vattenpelaren. CH4 oxidation kunde endast uppskattas i vattenpelaren i augusti, och i vattenpelarens ytskikt i juni och juli.