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A transfusão de plaquetas pode ser terapêutica quando indicada para interrupção de sangramento ativo ou profilática com o objetivo de prevenir hemorragias. Os concentrados de plaquetas apresentam um volume menor quando comparado ao sangue fresco total e ao plasma rico em plaquetas elevando a contagem plaquetária rapidamente minimizando, assim, a transfusão de componentes desnecessários e o risco de reações transfusionais o que no entanto podem ocorrer. Em cães, a literatura é escassa em relação à ocorrência de reações transfusionais frente ao emprego de concentrados de plaquetas. Sendo assim, este estudo tem como objetivo documentar a ocorrência de efeitos adversos em relação à administração de concentrados de plaquetas em cães em caráter clínico. Realizou-se a transfusão de concentrados de plaquetas em vinte e oito cães trombocitopênicos com manifestações clínicas de diáteses hemorrágicas ou antes de procedimentos cirúrgicos. Estes hemo componentes foram preparados por centrifugação diferencial seriada do sangue total padronizando-se o fracionamento sanguíneo para cães. Determinou-se um controle de qualidade destes concentrados monitorando-se o pH, níveis de glicose, temperatura de armazenamento, rendimento plaquetário, contaminação bacteriana e swirling. Adotou-se uma proporção de 1 concentrado de plaquetas para cada 10 Kg. Dentre os vinte e oito cães transfundidos, presenciou-se a ocorrência de reações adversas em dez pacientes (35,7%) caracterizadas por manifestações gastrintestinais (6/28), seguidas das alérgicas (5/28) e inflamatórias (2/28). A hipertermia, principal reação relatada em seres humanos, foi constatada apenas em um paciente. O incremento plaquetário observado em 1 e 24 horas foi considerado satisfatório na maioria dos cães transfundidos sendo, em média, de 38.000 e 31.000 plaquetas/µL respectivamente. / Platelet transfusion may be either therapeutic or praphylactic when used to interrupt active bleeding or to avoid it, respectively. Plate1et concentrates have a smaller volume when compared to fresh whole blood and to plate1et-rich plasma. Their use quickly increases plate1et counts and, therefore, minimizes unnecessary transfusion of blood components and subsequent transfusion reactions. Literature is scarce concerning transfusion reactions after the administration of platelet concentrates in dogs. Therefore, the objective of this study was to record c1inical adverse effects after its administration in dogs. Platelet concentrates were administered in twenty-eight thrombocytopenic dogs with c1inical signs of hemorrhage or before surgical procedures. These hemocomponents were prepared by serial differential centrifugation of the whole blood standardizing the whole blood fractionation method to dogs. Quality contraI of platelet concentrates was performed by monitoring pH, glucose, storage temperature, platelet count, bacterial contamination and swirling. The dose administrated was one unit per 10 kg. Transfusion reactions occurred in ten dogs (35.7%), characterized by gastrointestinal manifestations (6/28), followed by allergic (5/28) and inflammatory reactions (2/28). Hyperthermia, the most frequent1y reported reaction in humans, was observed in only one dog. The platelet increment observed 1 and 24 hours post-transfusion was considered satisfactory in the majority of the transfused dogs, being, on the average, 38,000 and 31,000 platelets/ µL, respectively.

Bacterial contamination of platelet concentrates (PCs) poses the highest transfusion-associated infectious risk with skin flora, such as Staphylococcus epidermidis and Staphylococcus capitis, being the predominant contaminants. These bacteria are able to form surface-attached aggregates or biofilms, which are present in the skin of healthy blood donors and can subsequently be isolated from contaminated PCs. Disinfection of the venipuncture area before donation with a combination of 2% chlorhexidine-gluconate and 70% isopropanol is used at Canadian Blood Services. However, not all bacteria are eliminated during skin disinfection since contaminated PCs are still captured during routine PC screening. In this thesis, the ability of biofilm-forming S. epidermidis and S. capitis to resist the currently used disinfectants was explored. It was demonstrated that although a combination of chlorhexidine and isopropanol has a bactericidal effect, it is unable to completely eradicate skin flora biofilms. Several countries have implemented Pathogen Inactivation Technologies (PITs) as a measure to help control transfusing bacterially-contaminated PCs by exposing PC units to ultra violet light. However, no investigations have been done to evaluate the ability of PITs against bacterial biofilms, which was one of the objectives of this thesis. Data revealed that the efficacy of a currently used PIT, the Mirasol® system, is similar for S. epidermidis present in PCs produced from whole blood inoculated with biofilm or non-biofilm cells. However, treatment effectiveness was strain dependent. In conclusion, further investigation to improve donor skin disinfection and PITs should be considered. Surveillance at Canadian Blood Services shows that contamination rates in single-donor apheresis PCs (Aph-PCs) is generally higher than in four-donor buffy coat platelet pools (BC-PCs). This study investigated whether the BC-PC production method contributes to this observation as BC-PCs are derived from WB that is left to rest overnight while Aph-PCs are collected directly from the donor. Data showed that WB hold during BC-PC production does not have a broad-spectrum bactericidal effect and therefore other factors contribute to low rates of contamination in BC-PCs. The work presented in this thesis provides an insight to bacterial residence and persistence during blood product manufacturing and makes suggestions for PC safety improvements.

A transfusão de plaquetas pode ser terapêutica quando indicada para interrupção de sangramento ativo ou profilática com o objetivo de prevenir hemorragias. Os concentrados de plaquetas apresentam um volume menor quando comparado ao sangue fresco total e ao plasma rico em plaquetas elevando a contagem plaquetária rapidamente minimizando, assim, a transfusão de componentes desnecessários e o risco de reações transfusionais o que no entanto podem ocorrer. Em cães, a literatura é escassa em relação à ocorrência de reações transfusionais frente ao emprego de concentrados de plaquetas. Sendo assim, este estudo tem como objetivo documentar a ocorrência de efeitos adversos em relação à administração de concentrados de plaquetas em cães em caráter clínico. Realizou-se a transfusão de concentrados de plaquetas em vinte e oito cães trombocitopênicos com manifestações clínicas de diáteses hemorrágicas ou antes de procedimentos cirúrgicos. Estes hemo componentes foram preparados por centrifugação diferencial seriada do sangue total padronizando-se o fracionamento sanguíneo para cães. Determinou-se um controle de qualidade destes concentrados monitorando-se o pH, níveis de glicose, temperatura de armazenamento, rendimento plaquetário, contaminação bacteriana e swirling. Adotou-se uma proporção de 1 concentrado de plaquetas para cada 10 Kg. Dentre os vinte e oito cães transfundidos, presenciou-se a ocorrência de reações adversas em dez pacientes (35,7%) caracterizadas por manifestações gastrintestinais (6/28), seguidas das alérgicas (5/28) e inflamatórias (2/28). A hipertermia, principal reação relatada em seres humanos, foi constatada apenas em um paciente. O incremento plaquetário observado em 1 e 24 horas foi considerado satisfatório na maioria dos cães transfundidos sendo, em média, de 38.000 e 31.000 plaquetas/µL respectivamente. / Platelet transfusion may be either therapeutic or praphylactic when used to interrupt active bleeding or to avoid it, respectively. Plate1et concentrates have a smaller volume when compared to fresh whole blood and to plate1et-rich plasma. Their use quickly increases plate1et counts and, therefore, minimizes unnecessary transfusion of blood components and subsequent transfusion reactions. Literature is scarce concerning transfusion reactions after the administration of platelet concentrates in dogs. Therefore, the objective of this study was to record c1inical adverse effects after its administration in dogs. Platelet concentrates were administered in twenty-eight thrombocytopenic dogs with c1inical signs of hemorrhage or before surgical procedures. These hemocomponents were prepared by serial differential centrifugation of the whole blood standardizing the whole blood fractionation method to dogs. Quality contraI of platelet concentrates was performed by monitoring pH, glucose, storage temperature, platelet count, bacterial contamination and swirling. The dose administrated was one unit per 10 kg. Transfusion reactions occurred in ten dogs (35.7%), characterized by gastrointestinal manifestations (6/28), followed by allergic (5/28) and inflammatory reactions (2/28). Hyperthermia, the most frequent1y reported reaction in humans, was observed in only one dog. The platelet increment observed 1 and 24 hours post-transfusion was considered satisfactory in the majority of the transfused dogs, being, on the average, 38,000 and 31,000 platelets/ µL, respectively.

В разделе сырьевая база угля для коксования описаны характеристики угольных концентратов обогатительных фабрик входящих в производственную шихту. Раздел определение размолоспособности угольных концентратов содержит описание методов определения размолоспособности угля и описан ситовый состав входящих угольных концентратов. В разделе прогнозирование качества кокса выполнен анализ засорения угольных концентратов породными и промпродуктовыми включениями, описан порядок расчетов комплексного показателя коксуемости шихт. / The section raw material base of coal for coking describes the characteristics of coal concentrates of processing plants included in the production charge. The section determination of the grinding capacity of coal concentrates contains a description of methods for determining the grinding capacity of coal and describes the sieve composition of the incoming coal concentrates. In the section predicting the quality of coke, the analysis of clogging of coal concentrates with rock and industrial product inclusions is performed, and the procedure for calculating the complex coking index of the charge is described.

A doença de von Willebrand (DvW) é uma coagulopatia hereditária, causada por defeitos qualitativos ou quantitativos do fator de von Willebrand. O tratamento e a prevenção das intercorrências da DvW são bastante dispendiosos e, em geral, se baseiam na administração de concentrado de Fator VIII/FvW (CFVIII/FvW) e/ou da Desmopressina (DDAVP). Em muitas situações, o DDAVP é um tratamento eficaz que não expõe os pacientes aos riscos de contaminação viral e apresenta custo inferior quando comparado ao CFVIII/FvW. No entanto, a dificuldade de diagnóstico e classificação da DvW, bem como o baixo número de pacientes que se submetem ao teste para avaliação da resposta ao DDAVP, restringem a indicação do DDAVP como alternativa terapêutica para esses pacientes. O objetivo deste estudo foi avaliar retrospectivamente a indicação, o uso e o custo dos medicamentos no tratamento de pacientes com DvW com DDAVP e CFVIII/FvW no Hemocentro de Belo Horizonte no período entre 2011 a 2013. Este estudo incluiu 124 (24,22%) pacientes com DvW atendidos no hemocentro. Em 18 pacientes (14,52%) o diagnóstico de DvW não pode ser confirmado. Doze pacientes (9,68%) não puderam ser classificados e 73 foram classificados como tipo 1, 19 como tipo 2 e 2 pacientes como tipo 3. Oitenta e um pacientes fizeram o teste de DDAVP, sendo que 87,65% foram considerados responsivos. Nos pacientes tipo 1, a taxa de resposta ao DDAVP foi de 92%. Quase 32% dos pacientes tipo 1 não realizaram o teste. No período avaliado, foram utilizadas 3.794mcg de DDAVP (R$13.165,18) e 1.582.250 UI de CFVIII/FvW (R$1.075.930,00). Vinte por cento dos pacientes responsivos ao DDAVP utilizaram CFVIII/FvW em indicações onde o DDAVP poderia ter sido considerado (69.200UI de CFVIII/FvW versus 131 ampolas de DDAVP). Nos pacientes potencialmente responsivos ao DDAVP 108.700UI de CFVIII/FvW (R$73.916,00) poderiam ter sido substituídas por 247 ampolas de DDAVP (R$3.428,36). A escolha do DDAVP nessas situações poderia representar uma economia de 95,7% do valor gasto no tratamento do grupo de 27 pacientes responsivos e potencialmente responsivos ao DDAVP e 10,6% do valor total gasto para todo o tratamento dos pacientes no período do estudo. Estudos mais complexos de farmacoeconomia serão necessários para avaliar a magnitude da economia gerada com esse uso. O presente estudo mostrou que o DDAVP é uma alternativa terapêutica de menor custo, cuja indicação e utilização podem ser ampliadas no tratamento dos pacientes com DvW. Dessa maneira, a implementação de estratégias visando melhorar o diagnóstico, a classificação da doença, o acesso à testagem quanto à resposta ao DDAVP, bem como a conscientização dos profissionais de saúde e pacientes, quanto ao custo e segurança do DDAVP podem contribuir para o uso racional dos recursos destinados a essa parcela da população. / Von Willebrand disease (VWD) is a hereditary coagulopathy caused by qualitative or quantitative defects on von Willebrand factor. The treatment and the prevention of VWD complications is quite expensive and is generally based on the administration of vWF:FVIII Concentrates and/or Desmopressin (DDAVP). In many situations, DDAVP is an effective treatment that does not expose patients to viral contamination risks and presents a lower cost when compared to vWF:FVIII concentrates. However, the difficulty of diagnosis and classification of VWD, as well as the low number of patients tested to their responsiveness to DDAVP, restrict the use of DDAVP as an alternative treatment for these patients. The aim of this study was to evaluate retrospectively the clinical indications, the use and the cost of treatment of VWD patients with DDAVP and vWF:FVIII concentrates in the Blood Center of Belo Horizonte between 2011 and 2013. This study enrolled 124 (24.22%) VWD patients attended at the Blood Center.For18 (14.52%) patients, the diagnosis of VWD could not be confirmed. Twelve patients (9.68%) could not be classified and 73patients were classified as type 1, 19 as type 2 and 2 as type 3. Eighty-one patients were tested for DDAVP response and 87.65% (n=71) were considered responsive for the treatment. For type 1 VWD patients, the response rate to DDAVP was 92%. Almost 32% of type 1 VWD patients were not tested. In the period evaluated, 3,794mcg of DDAVP (R$ 13,165.18) and 1,582,250 IU of vWF:FVIII concentrates (R$ 1,075,930.00) were used. Between the cases with clinical indication of DDAVP use, 20% patients used vWF:FVIII concentrates (69.200UI of vWF:FVIII versus 131ampoules of DDAVP). In patients with good responsive to DDAVP, 108,700 IU of vWF:FVIII concentrates used (R$ 73,916.00) could be replaced by 247 ampoules of DDAVP (R$ 3,428.36). The choice of DDAVP in these situations could represent an economy of 95.7% of the value spent on the treatment of the 27 responsive and potentially responsive patients to DDAVP and 10.6% of the total value spent for the entire treatment of patients in the study period. More detailed studies of pharmacoeconomics are necessary to assess the magnitude of the economy generated by the use of DDAVP. This study demonstrated that DDAVP is a lower cost therapeutic alternative whose indication and use can be enhanced in the treatment of VWD patients. In this context, adoption of strategies to improve the differential diagnosis, expand the DDAVP responsiveness test, and aware health professionals and patients about the costs and safety use of DDAVP, could contribute to the rational use of resources designated to treatment of VWD.

Arsenic contamination of groundwater associated with mining operations is a widespread problem across the globe. The release of arsenic (As) into the environment occurs naturally by oxidation of exposed sulfide minerals. In the case of gold ores, the mining and beneficiation may also produce As-bearing wastes and this can accelerate the natural mechanisms of As mobilization. The Bakyrchik is the largest gold deposit in Kazakhstan and one of the largest in the world. Gold (Au) is dispersed in pyrite and arsenopyrite in the form of microscopic inclusions. Despite the fact that only 10% of gold ore has been mined to date, it has left behind a dangerous As-containing legacy. Speciation of As has been determined for samples from Bakyrchik to understand the post-processing environment and the mobility of arsenic in the mining-influenced area. As(III) and As(V) have been detected in water samples using HPLC-ICP-MS. The variability of As species across the narrow pH and Eh range indicates that biogeochemical processes can play a role in the speciation of As in water at the study site. In order to understand processes controlling As mobilization in water, the solid phase speciation of As in Bakyrchik sediments, soil, and metallurgical processing products has been investigated using XRD and EPMA. This revealed arsenopyrite, As-bearing pyrite, and their alteration products containing up to 25% As, iron oxides and oxyhydroxides (with up to 2.5% As), haidingerite, and calcium arsenate in studied samples. Sequential extraction demonstrated that in soil and sediment samples As is associated mainly with Al and amorphous Fe oxyhydroxides. Results suggest that the main mechanisms controlling As mobility in Bakyrchik are dilution with regional waters, adsorption onto iron and aluminium oxyhydroxides, and co-precipitation of dissolved As with alteration products of sulfide minerals. Assessment of As bioaccessibility through inhalation demonstrates its strong dependence on the mineralogy rather than on total As content of the solid samples. Calculated cancer and non-cancer risks of inhalation exposure imply that all samples are highly hazardous for human health. With the depletion of the oxide lode ore deposits, gold extraction is moving towards the mining of technologically difficult ores, such as those found at Bakyrchik. A new method of Au recovery from double refractory Au-As-bearing concentrates has been developed, allowing recovery of 97% of Au, and the conversion of up to 95% As into iron-arsenic alloy. Fe-As alloy can contain up to 40% As, and do not require further solidification/stabilisation prior to disposal. The method has been published as a patent with the Patent Office of the Republic of Kazakhstan. Quantitative phase composition of the Fe-As alloy, has been determined by EPMA, QEMSCAN, X-ray and neutron diffraction. Toxicity and solubility of Fe-As alloy in aqueous solutions have been characterised. High-temperature structural behaviour of Fe-As alloy and Fe$_{2}$As in inert atmosphere has been determined by $\textit{in situ}$ synchrotron XRD. Results of the study support the development of the new method as an efficient alternative for processing double refractory Au-As-bearing concentrates.

Coagulase negative staphylococci (CoNS) are the most prevalent bacterial contaminants of platelet concentrates (PCs), and have been implicated in severe and fatal transfusion reactions. Of this group, Staphylococcus epidermidis is most frequently identified. The preliminary objective of this thesis was to confirm that S. epidermidis could form biofilms under platelet storage conditions. This was achieved using a modified crystal violet staining assay to detect plastic-adherent bacterial cells and examination of attachment processes by scanning electron microscopy. A collection of CoNS isolated from PCs obtained from reportedly healthy donors was then assessed for biofilm-forming potential at the genetic and phenotypic level. Despite the presumable commensal origin of these isolates, a high proportion of S. epidermidis strains displayed a biofilm positive phenotype. The threat of S. epidermidis biofilm formation during platelet storage identified herein signifies that any alterations made to platelet storage protocols should be evaluated with consideration of this risk. The advent of platelet additive solutions (PASs) as an alternative to plasma for PC storage provides a relevant example, since little is known about the effect of PAS on contaminant bacteria, and vice versa. Growth and biofilm formation by S. epidermidis and the Gram-negative bacterium Serratia liquefaciens were measured in PAS- or plasma-PCs over 5 days, simulating standard platelet storage conditions, after initial inoculation with low, clinically relevant bacterial concentrations. Assays for platelet quality were performed simultaneously. Only S. liquefaciens exhibited a slower doubling time in plasma-PCs than in PAS-PCs. Biofilm formation by both species was reduced during storage in PAS-PCs, increasing bacteria availability for detection. Although S. liquefaciens adversely affected platelet quality in both media, S. epidermidis contamination did not. Ultimately, culture-based detection remains the earliest indicator of bacterial presence in PAS-PCs. Lastly, since formation of platelet-bacteria aggregates is largely based on receptor-ligand interactions, it was postulated that biofilm formation by contaminant bacteria could be abrogated by receptor shielding. Methoxypoly(ethylene glycol) was applied to covalently modify the platelet surface using a process termed ‘PEGylation’. It is herein demonstrated that PEGylation of PCs inoculated with S. epidermidis results in significantly reduced bacterial binding and biofilm formation during platelet storage.

Coagulase negative staphylococci (CoNS) are the most prevalent bacterial contaminants of platelet concentrates (PCs), and have been implicated in severe and fatal transfusion reactions. Of this group, Staphylococcus epidermidis is most frequently identified. The preliminary objective of this thesis was to confirm that S. epidermidis could form biofilms under platelet storage conditions. This was achieved using a modified crystal violet staining assay to detect plastic-adherent bacterial cells and examination of attachment processes by scanning electron microscopy. A collection of CoNS isolated from PCs obtained from reportedly healthy donors was then assessed for biofilm-forming potential at the genetic and phenotypic level. Despite the presumable commensal origin of these isolates, a high proportion of S. epidermidis strains displayed a biofilm positive phenotype. The threat of S. epidermidis biofilm formation during platelet storage identified herein signifies that any alterations made to platelet storage protocols should be evaluated with consideration of this risk. The advent of platelet additive solutions (PASs) as an alternative to plasma for PC storage provides a relevant example, since little is known about the effect of PAS on contaminant bacteria, and vice versa. Growth and biofilm formation by S. epidermidis and the Gram-negative bacterium Serratia liquefaciens were measured in PAS- or plasma-PCs over 5 days, simulating standard platelet storage conditions, after initial inoculation with low, clinically relevant bacterial concentrations. Assays for platelet quality were performed simultaneously. Only S. liquefaciens exhibited a slower doubling time in plasma-PCs than in PAS-PCs. Biofilm formation by both species was reduced during storage in PAS-PCs, increasing bacteria availability for detection. Although S. liquefaciens adversely affected platelet quality in both media, S. epidermidis contamination did not. Ultimately, culture-based detection remains the earliest indicator of bacterial presence in PAS-PCs. Lastly, since formation of platelet-bacteria aggregates is largely based on receptor-ligand interactions, it was postulated that biofilm formation by contaminant bacteria could be abrogated by receptor shielding. Methoxypoly(ethylene glycol) was applied to covalently modify the platelet surface using a process termed ‘PEGylation’. It is herein demonstrated that PEGylation of PCs inoculated with S. epidermidis results in significantly reduced bacterial binding and biofilm formation during platelet storage.

Coagulase negative staphylococci (CoNS) are the most prevalent bacterial contaminants of platelet concentrates (PCs), and have been implicated in severe and fatal transfusion reactions. Of this group, Staphylococcus epidermidis is most frequently identified. The preliminary objective of this thesis was to confirm that S. epidermidis could form biofilms under platelet storage conditions. This was achieved using a modified crystal violet staining assay to detect plastic-adherent bacterial cells and examination of attachment processes by scanning electron microscopy. A collection of CoNS isolated from PCs obtained from reportedly healthy donors was then assessed for biofilm-forming potential at the genetic and phenotypic level. Despite the presumable commensal origin of these isolates, a high proportion of S. epidermidis strains displayed a biofilm positive phenotype. The threat of S. epidermidis biofilm formation during platelet storage identified herein signifies that any alterations made to platelet storage protocols should be evaluated with consideration of this risk. The advent of platelet additive solutions (PASs) as an alternative to plasma for PC storage provides a relevant example, since little is known about the effect of PAS on contaminant bacteria, and vice versa. Growth and biofilm formation by S. epidermidis and the Gram-negative bacterium Serratia liquefaciens were measured in PAS- or plasma-PCs over 5 days, simulating standard platelet storage conditions, after initial inoculation with low, clinically relevant bacterial concentrations. Assays for platelet quality were performed simultaneously. Only S. liquefaciens exhibited a slower doubling time in plasma-PCs than in PAS-PCs. Biofilm formation by both species was reduced during storage in PAS-PCs, increasing bacteria availability for detection. Although S. liquefaciens adversely affected platelet quality in both media, S. epidermidis contamination did not. Ultimately, culture-based detection remains the earliest indicator of bacterial presence in PAS-PCs. Lastly, since formation of platelet-bacteria aggregates is largely based on receptor-ligand interactions, it was postulated that biofilm formation by contaminant bacteria could be abrogated by receptor shielding. Methoxypoly(ethylene glycol) was applied to covalently modify the platelet surface using a process termed ‘PEGylation’. It is herein demonstrated that PEGylation of PCs inoculated with S. epidermidis results in significantly reduced bacterial binding and biofilm formation during platelet storage.