A emergência de resistência à vancomicina no mundo iniciou-se no final dos anos 80, sendo primeiro documentada na parte ocidental da Europa e posteriormente nos EUA. Depois disso, o isolamento de enterococos resistentes à vancomicina (VRE - do inglês, vancomycin-resistant enterococci) tem sido continuamente reportado em diversas localizações geográficas, inclusive no Brasil. As infecções nosocomiais causadas por enterococos são grandes desafios para os médicos devido à ocorrência de isolados resistentes a múltiplos antibióticos. Diversos métodos de tipagem molecular têm sido utilizados para estudar a epidemiologia de VRE. Neste trabalho, foi realizada a caracterização genética da resistência à vancomicina e epidemiologia molecular de VREs isolados de pacientes de dois hospitais de Ribeirão Preto, o Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP) e a Santa Casa de Misericórdia de Ribeirão Preto (SCMRP), no período de setembro de 2008 a setembro de 2010. Foram estudados também os primeiros VREs isolados no HCFMRP-USP, em meados de 2005/2006. Foram determinadas as espécies e os genótipos de 53 VREs, pela reação da polimerase em cadeia (PCR), e todos eram E. faecium e apresentavam o gene vanA. Todos E. faecium isolados dos 2 hospitais em estudo apresentaram CIM para vancomicina >256?g/mL pelo Etest®, já daptomicina mostrou valores de CIM dentro do limite de sensibilidade para todos os enterococos analisados. Com relação aos fatores de virulência, foi evidente a predominância dos genes acm e esp nos E. faecium estudados. Os primeiros VREfm (do inglês, vancomycin-resistant E. faecium) isolados em meados de 2005/2006 de pacientes do HCFMRP-USP apresentaram o transposon Tn1546 intacto, já todos os E. faecium isolados do HCFMRP-USP e da SCMRP, no período de setembro de 2008 a setembro de 2010, apresentaram produto de amplificação maior do que os 4,4kb esperados para grupamento gênico vanRSHAX. Resultados de overlapping PCR e sequenciamento da região do transposon que amplificou fragmento de DNA com tamanho maior que o esperado utilizando primers P11-P12, mostraram que 81% (43 VREfm) isolados nos dois hospitais em estudo, no período de setembro de 2008 a setembro de 2010, apresentaram deleção da extremidade esquerda do Tn1546 e insersão (IS1251), entre genes vanS e vanH. A análise da PFGE dos VREfm em estudo mostrou que havia ocorrido disseminações clonais com determinados perfis de PFGE em períodos específicos. O fato dos primeiros VREfm terem apresentado perfil de PFGE diferente da maioria dos isolados, não permitiu que se determinasse o ancestral comum por PFGE, mas resultados de MLST mostraram que VREfm isolados, no período de 2008-2010, podem ser descendentes diretos destes cinco primeiros VREfm ou podem ter evoluído de um mesmo ancestral comum. A análise da tipagem por MLST de 31 linhagens de VREfm selecionadas a partir dos resultados de PFGE, mostrou que havia 9 STs diferentes, dentre estes, sendo 5 STs novos (656, 657, 658, 659 e 660). Os STs predominantes foram STs 412 e 478. Todos STs identificados pertenciam ao complexo clonal 17 (CC17), com exceção do ST658 que era um singleton. O ST78 que vem se disseminando mundialmente, foi identificado pela primeira vez no Brasil em linhagens do presente estudo. E, por fim, a tipagem por MLST comprovou o que já havia sido determinado pelos resultados de PFGE, que existe relação clonal entre linhagens isoladas nos dois hospitais estudados de Ribeirão Preto. / World reports on vancomycin resistance emerged in the late 1980s and first documented in Western Europe and later in the United States. Since then, isolation of vancomycin-resistant enterococci (VRE) has been continuously reported in several geographic locations, including Brazil. The widespread occurrence of strains resistant to multiple antibiotics present a challenge to clinicians when treating enterococci caused nosocomial infections. Several molecular typing methods have been used to study the epidemiology of VRE. In this study, genetic characterization of vancomycin resistance and molecular epidemiology were performed in VREs isolated from patients in two hospitals in Ribeirão Preto, Sao Paulo/Brazil, the University Hospital of the Faculty of Medicine of Ribeirao Preto, University of Sao Paulo (HCFMRP-USP) and the Santa Casa de Misericórdia de Ribeirão Preto (SCMRP), from September 2008 to September 2010. The first five VREs isolated in the HCFMRP-USP, in mid 2005/2006 were also included in this study. Species and genotypes of 53 VREs determined by the polymerase chain reaction (PCR) were all E. faecium and had the vanA gene. MICs for vancomycin determined by Etest® were >256?g/mL for all E. faecium isolated in the two hospitals, whereas daptomycin showed MIC values within the limit of susceptibility for all the enterococci analyzed. acm and esp genes predominated as virulence factors. The first five vancomycin resistant E. faecium (VREfm) isolated in mid 2005/2006 showed an intact Tn1546 transposon, whereas all E. faecium isolated later, September 2008 to September 2010, gave a larger amplified DNA fragment than the expected 4,4kb gene cluster vanRSHAX. Results of overlapping PCR and sequencing (primers P11-P12) of the transposon region that amplified the larger than expected DNA fragment showed that 81% (n=43) of the these VREfm had a deletion of the left end of Tn1546 and also a IS1251, between the vanS and vanH genes. The analysis of VREfm PFGEs indicated the occurrence of clonal disseminations with some PFGE profiles at specific times. The different PFGE profiles of the first VREfm (2005-2006) in relation to the latter isolates showed that the common ancestor could not be determined by PFGE. However, MLST results indicated that VREfm isolated, in the period from 2008 to 2010, could be direct descendants of the first five VREfm or could have evolved from a common ancestor. MLST analysis of 31 VREfm isolates selected according to the PFGE results, showed that there were nine different STs, among these five new STs (656, 657, 658, 659, 660). The predominant STs were ST412 and 478. All STs identified belonged to clonal complex 17 (CC17), except for ST658, a singleton. The ST78 that has spread worldwide is being identified in Brazil for first time in this study. MLST confirmed PFGE results showing that there is a clonal link between strains isolated in the two hospitals of Ribeirao Preto, Sao Paulo, Brazil.

A emergência de resistência à vancomicina no mundo iniciou-se no final dos anos 80, sendo primeiro documentada na parte ocidental da Europa e posteriormente nos EUA. Depois disso, o isolamento de enterococos resistentes à vancomicina (VRE - do inglês, vancomycin-resistant enterococci) tem sido continuamente reportado em diversas localizações geográficas, inclusive no Brasil. As infecções nosocomiais causadas por enterococos são grandes desafios para os médicos devido à ocorrência de isolados resistentes a múltiplos antibióticos. Diversos métodos de tipagem molecular têm sido utilizados para estudar a epidemiologia de VRE. Neste trabalho, foi realizada a caracterização genética da resistência à vancomicina e epidemiologia molecular de VREs isolados de pacientes de dois hospitais de Ribeirão Preto, o Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP) e a Santa Casa de Misericórdia de Ribeirão Preto (SCMRP), no período de setembro de 2008 a setembro de 2010. Foram estudados também os primeiros VREs isolados no HCFMRP-USP, em meados de 2005/2006. Foram determinadas as espécies e os genótipos de 53 VREs, pela reação da polimerase em cadeia (PCR), e todos eram E. faecium e apresentavam o gene vanA. Todos E. faecium isolados dos 2 hospitais em estudo apresentaram CIM para vancomicina >256?g/mL pelo Etest®, já daptomicina mostrou valores de CIM dentro do limite de sensibilidade para todos os enterococos analisados. Com relação aos fatores de virulência, foi evidente a predominância dos genes acm e esp nos E. faecium estudados. Os primeiros VREfm (do inglês, vancomycin-resistant E. faecium) isolados em meados de 2005/2006 de pacientes do HCFMRP-USP apresentaram o transposon Tn1546 intacto, já todos os E. faecium isolados do HCFMRP-USP e da SCMRP, no período de setembro de 2008 a setembro de 2010, apresentaram produto de amplificação maior do que os 4,4kb esperados para grupamento gênico vanRSHAX. Resultados de overlapping PCR e sequenciamento da região do transposon que amplificou fragmento de DNA com tamanho maior que o esperado utilizando primers P11-P12, mostraram que 81% (43 VREfm) isolados nos dois hospitais em estudo, no período de setembro de 2008 a setembro de 2010, apresentaram deleção da extremidade esquerda do Tn1546 e insersão (IS1251), entre genes vanS e vanH. A análise da PFGE dos VREfm em estudo mostrou que havia ocorrido disseminações clonais com determinados perfis de PFGE em períodos específicos. O fato dos primeiros VREfm terem apresentado perfil de PFGE diferente da maioria dos isolados, não permitiu que se determinasse o ancestral comum por PFGE, mas resultados de MLST mostraram que VREfm isolados, no período de 2008-2010, podem ser descendentes diretos destes cinco primeiros VREfm ou podem ter evoluído de um mesmo ancestral comum. A análise da tipagem por MLST de 31 linhagens de VREfm selecionadas a partir dos resultados de PFGE, mostrou que havia 9 STs diferentes, dentre estes, sendo 5 STs novos (656, 657, 658, 659 e 660). Os STs predominantes foram STs 412 e 478. Todos STs identificados pertenciam ao complexo clonal 17 (CC17), com exceção do ST658 que era um singleton. O ST78 que vem se disseminando mundialmente, foi identificado pela primeira vez no Brasil em linhagens do presente estudo. E, por fim, a tipagem por MLST comprovou o que já havia sido determinado pelos resultados de PFGE, que existe relação clonal entre linhagens isoladas nos dois hospitais estudados de Ribeirão Preto. / World reports on vancomycin resistance emerged in the late 1980s and first documented in Western Europe and later in the United States. Since then, isolation of vancomycin-resistant enterococci (VRE) has been continuously reported in several geographic locations, including Brazil. The widespread occurrence of strains resistant to multiple antibiotics present a challenge to clinicians when treating enterococci caused nosocomial infections. Several molecular typing methods have been used to study the epidemiology of VRE. In this study, genetic characterization of vancomycin resistance and molecular epidemiology were performed in VREs isolated from patients in two hospitals in Ribeirão Preto, Sao Paulo/Brazil, the University Hospital of the Faculty of Medicine of Ribeirao Preto, University of Sao Paulo (HCFMRP-USP) and the Santa Casa de Misericórdia de Ribeirão Preto (SCMRP), from September 2008 to September 2010. The first five VREs isolated in the HCFMRP-USP, in mid 2005/2006 were also included in this study. Species and genotypes of 53 VREs determined by the polymerase chain reaction (PCR) were all E. faecium and had the vanA gene. MICs for vancomycin determined by Etest® were >256?g/mL for all E. faecium isolated in the two hospitals, whereas daptomycin showed MIC values within the limit of susceptibility for all the enterococci analyzed. acm and esp genes predominated as virulence factors. The first five vancomycin resistant E. faecium (VREfm) isolated in mid 2005/2006 showed an intact Tn1546 transposon, whereas all E. faecium isolated later, September 2008 to September 2010, gave a larger amplified DNA fragment than the expected 4,4kb gene cluster vanRSHAX. Results of overlapping PCR and sequencing (primers P11-P12) of the transposon region that amplified the larger than expected DNA fragment showed that 81% (n=43) of the these VREfm had a deletion of the left end of Tn1546 and also a IS1251, between the vanS and vanH genes. The analysis of VREfm PFGEs indicated the occurrence of clonal disseminations with some PFGE profiles at specific times. The different PFGE profiles of the first VREfm (2005-2006) in relation to the latter isolates showed that the common ancestor could not be determined by PFGE. However, MLST results indicated that VREfm isolated, in the period from 2008 to 2010, could be direct descendants of the first five VREfm or could have evolved from a common ancestor. MLST analysis of 31 VREfm isolates selected according to the PFGE results, showed that there were nine different STs, among these five new STs (656, 657, 658, 659, 660). The predominant STs were ST412 and 478. All STs identified belonged to clonal complex 17 (CC17), except for ST658, a singleton. The ST78 that has spread worldwide is being identified in Brazil for first time in this study. MLST confirmed PFGE results showing that there is a clonal link between strains isolated in the two hospitals of Ribeirao Preto, Sao Paulo, Brazil.

Sweden has goals to reach net-zero emissions by 2045. Although electricity sector is almost fossil free, industry & transport still rely on fossil fuels. Ambitious initiatives such as HYBRIT, growth of EV market & expansion of wind power aim to expedite emission reduction. Decarbonization of transport, industry and large-scale wind & solar PV integration in the future necessitates studying energy system of Sweden at national scale in the context of sector coupling, external transmission & storage technologies. Therefore, this study aims to evaluate the impact of thermal energy storage, hydrogen storage and batteries via Power-to-heat & Power-to-hydrogen strategies in the future Swedish energy system (2045) with high proportions of wind power. Two scenarios SWE_2045 & NFF_2045 were formulated to represent two distinct energy systems of the future. The SWE_2045 energy system still relies on fossil fuels, but to a lower extent compared to 2019 level and has increased levels of electrification and biofuels in the transport and industrial sectors. In comparison, the fossil fuels are completely removed in NFF_2045 and the industrial sector has significant demand for electrolytic hydrogen. Both the scenarios were simulated using EnergyPLAN, a deterministic energy system model, under each storage technology. The results indicate that HPs coupled with TES has the potential to increase wind integration from 29.12% to 31.8% in SWE_2045 and 26.78% to 29.17% in NFF_2045. HP & TES also reduces heat production from boilers by 67% to 72% depending on the scenario, leading to overall reduction in total fuel and annual costs by at least 2.5% and 0.5% respectively. However, for wind integration of 31.1% in SWE_2045 the annual cost increases by 5.1% with hydrogen storage compared to TES. However, hydrogen storage shows better performance in NFF_2045, wherein the wind integration increases from 26.78% to 29.3%. Furthermore, increasing hydrogen storage for a lower wind capacity (60 GW) in NFF_2045 reduces both electricity import and export while simultaneously increasing the contribution of storage in fulfilling the hydrogen demand from 1.62% to 6.2%. Compared to TES and HS, the contribution of battery storage is minimal in sector integration. For increase in wind integration of 28% to 29%, the annual cost of a system with battery storage is 1.3% to 2% higher than that of the system with TES and hydrogen storage respectively. Therefore, HPs coupled with TES can improve flexibility in both scenarios. Hydrogen storage is not a promising option if the end goal is only to store excess electricity, as shown by the results in SWE_2045. However, it demonstrates better utilization in terms of wind integration, reduction in electricity import and export when there is a considerable demand for hydrogen, as in the case of NFF_2045. / Sverige ligger i framkant när det gäller avkarbonisering och har mål att nå nettonollutsläpp till 2045. Även om elsektorn är nästan fossilfri, är industri och transport fortfarande beroende av fossila bränslen. Ambitiösa initiativ som Hydrogen Breakthrough Ironmaking Technology (HYBRIT), tillväxt av elbilsmarknaden och expansion av vindkraft syftar till att påskynda utsläppsminskningar. Dekarbonisering av transport, industri och storskalig vind- och solcellsintegrering i framtiden kräver att man studerar Sveriges energisystem i nationell skala i samband med sektorskoppling, extern transmissions- och lagringsteknik.  Därför syftar denna studie till att bestämma effekten av termisk energilagring, vätelagring och batterier via Power-to-heat & Power-to-hydrogen-strategier i det framtida svenska energisystemet (2045) med höga andelar vindkraft. Två scenarier SWE_2045 & NFF_2045 formulerades för att representera två distinkta framtidens energisystem. Energisystemet SWE_2045 är fortfarande beroende av fossila bränslen, men i lägre utsträckning jämfört med 2019 års nivå och har ökat nivåerna av elektrifiering och biobränslen inom transport- och industrisektorn. Som jämförelse är de fossila bränslena helt borttagna i NFF_2045-scenariot där transportsektorn endast är beroende av el och biobränslen, medan industrisektorn har en betydande efterfrågan på elektrolytiskt väte. Båda energisystemen simuleras med EnergyPLAN, en deterministisk energisystemmodell, för olika testfall under varje lagringsteknik. Resultatet av simuleringen bedömdes i termer av kritisk överskottselproduktion, potential för ytterligare vindintegration, total bränslebalans i systemet och årliga kostnader.  Resultatet indikerar att värmepumpar i kombination med termisk energilagring kan förbättra flexibiliteten i båda scenarierna genom att minska den kritiska överskottselproduktionen och bränsleförbrukningen samtidigt som vindintegrationen förbättras. Vätgaslagring är inget lovande alternativ om målet är att endast lagra överskottsel, vilket framgår av vindintegrationsnivåerna i SWE_2045. Det förbättrar dock vindintegration och tillförlitlighet avsevärt när det finns en betydande efterfrågan på vätgas i NFF_2045. Som jämförelse är batteriernas bidrag till vindintegration minimalt i båda scenarierna i samband med sektorintegration på grund av utnyttjandet av överskottsel av värmepumpar och extern överföring av restel. Valet av lagringsteknik i framtiden beror dock på dess tekniska ekonomiska utveckling och energipolitik.

Climate change drives policymakers to reduce emissions and enhance the integration of variable renewable energy sources (VRES) into the power system. Wind power is considered among the most beneficial VRES as it can generate cost-effectively carbon-free electricity but comes with inherent intermittency. Hydropower is a proposed solution among the research community to handle VRES output volatility and ensure balanced energy output to the electricity grid. This thesis addresses the problem by investigating the integration of intermittent wind power into a hydropower system cost-effectively. The research question "How does the integration of wind power affect the hydro operations and the cost of purchased electricity?" is answered within the Design Science Research framework by optimizing a subset of the Røldal-Suldal hydropower system in Norway's NO2 region. The cost-minimization model utilizes historical data from 2018 on water inflows, hourly electricity prices, hourly wind production, and hourly energy consumption for a smelter within the NO2 zone. To reduce the 8,760-time steps and computational concerns, the kmeans clustering algorithm is implemented to obtain four representative weeks. A multiperiod linear programming model is structured to assess the joint operation of wind and hydropower while ensuring a minimum energy production to satisfy the system's power demands. A benchmark scenario with no wind capacity is formed to serve as the basis for comparisons. Ten scenarios with 100-MW incremental steps of wind capacity are implemented. The minimized cost for the benchmark scenario is €104,981,312.34, with electricity purchases covering more than 75% of the energy demand and hydropower satisfying the remaining 25%. Adding 100 MW of wind capacity reduces costs by more than €2,000,000, restricting the purchased energy’s share by 1.49%, which is the equivalent increased share of wind power during each incremental step. A wind capacity of 1,000 MW leads to a 21.24% cost reduction. Hydropower production remains unaffected by the wind integration based on terminal values of reservoir level or turbined water volume. However, the distribution of hydropower production throughout the year changes after installing wind capacity enabling hydropower to utilize stored water optimally to minimize the costs of purchasing energy. A sensitivity analysis to assess the uncertainties tied with the model coefficients shows that increasing initial reservoir levels and adding 1,000 MW of wind capacity is the most influential factor in the optimization model.