The Marco Polo mission: a sample return from a low-albedo Near Earth Object in the ESA Cosmic Vision Program 2015-2025

Marco Polo is a sample return mission to a Near-Earth Object (NEO) which was originally proposed as a joint European-Japanese mission for the scientific program Cosmic Vision 2015-2025 of the European Space Agency (ESA) in June 2007 and selected for an assessment study until fall 2009. The main goal of this mission is to return a sample from a dark taxonomic type (low albedo) NEO for detailed laboratory analysis in order to answer questions related to planetary formation, evolution and the origin of Life. In addition, it will provide detailed information on the physical and chemical properties of a body belonging to the population of potential Earth impactors, and therefore it is also directly relevant to the problems of risk assessment and mitigation. We review basic information on NEOs, potential targets for a sample return mission and the Marco Polo mission, with emphasis on their relevance to impact risk assessment and mitigation. More details on the Marco Polo mission and scientific objectives can be found in [1]

Human Risk Assessment and Mitigation Using Bow Tie Strategy

Human reliability assessment (HRA) techniques are used for quantifying human error probability for the purpose of providing feedback regarding the overall performance, and most importantly, safety of the system. Performing HRA involves various activities, including task analysis, conducting experiments, which have been found generally difficult, time-consuming and costly. In this project, the whole process will be based on HRA methodology. For problem identification, a survey and interview are conducted. The task analysis of the finding was then constructed and the cause of human error is identified using human HAZOP and to be considered in Fault Tree Analysis (FTA) while all the controls will be developed. The Event Tree Analysis then developed based on consequences of the human error and all the control will be developed as well. The analysis then combined and Bow-Tie analysis is developed

A Capability-Centric Approach to Cyber Risk Assessment and Mitigation

Cyber-enabled systems are increasingly ubiquitous and interconnected, showing up in traditional enterprise settings as well as increasingly diverse contexts, including critical infrastructure, avionics, cars, smartphones, home automation, and medical devices. Meanwhile, the impact of cyber attacks against these systems on our missions, business objectives, and personal lives has never been greater. Despite these stakes, the analysis of cyber risk and mitigations to that risk tends to be a subjective, labor-intensive, and costly endeavor, with results that can be as suspect as they are perishable. We identified the following gaps in those risk results: concerns for (1) their repeatability/reproducibility, (2) the time required to obtain them, and (3) the completeness of the analysis per the degree of attack surface coverage. In this dissertation, we consider whether it is possible to make progress in addressing these gaps with the introduction of a new artifact called “BluGen.” BluGen is an automated platform for cyber risk assessment that employs a set of new risk analytics together with a highly-structured underlying cyber knowledge management repository. To help evaluate the hypotheses tied to the gaps identified, we conducted a study comparing BluGen to a cyber risk assessment methodology called EVRA. EVRA is representative of current practice and has been applied extensively over the past eight years to both fielded systems and systems under design. We used Design Science principles in the construction and investigation of BluGen, during which we considered each of the three gaps. The results of our investigation found support for the hypotheses tied to the gaps that BluGen is designed to address. Specifically, BluGen helps address the first gap by virtue of its methods/analytics executing as deterministic, automated processes. In the same way, BluGen helps address the second gap by producing its results at machine speeds in no worse than quadratic time complexity, seconds in this case. This result compares to the 25 hours that the EVRA team required to perform the same analysis. BluGen helps to address the third gap via its use of an underlying knowledge repository of cyber-related threats, mappings of those threats to cyber assets, and mappings of mitigations to the threats. The results show that manual analysis using EVRA covered about 12% of the attack surface considered by BluGen

BluGen: An Analytic Framework for Mission-Cyber Risk Assessment and Mitigation Recommendation

Systems security engineering (SSE) is a complex, manually intensive process, with implications for cost, time required, and repeatability/reproducibility. This paper describes BluGen, an analytic framework that generates risk plots and recommends prioritized mitigations for a target mission/system environment based on a stated level of threat and risk tolerance. The goal is to give working system security engineers a head start in their analysis. We describe BluGen in the context of Design Science Research and evaluate accordingly

Risk assessment and mitigation of e-scooter crashes with naturalistic driving data

Recently, e-scooter-involved crashes have increased significantly but little information is available about the behaviors of on-road e-scooter riders. Most existing e-scooter crash research was based on retrospectively descriptive media reports, emergency room patient records, and crash reports. This paper presents a naturalistic driving study with a focus on e-scooter and vehicle encounters. The goal is to quantitatively measure the behaviors of e-scooter riders in different encounters to help facilitate crash scenario modeling, baseline behavior modeling, and the potential future development of in-vehicle mitigation algorithms. The data was collected using an instrumented vehicle and an e-scooter rider wearable system, respectively. A three-step data analysis process is developed. First, semi-automatic data labeling extracts e-scooter rider images and non-rider human images in similar environments to train an e-scooter-rider classifier. Then, a multi-step scene reconstruction pipeline generates vehicle and e-scooter trajectories in all encounters. The final step is to model e-scooter rider behaviors and e-scooter-vehicle encounter scenarios. A total of 500 vehicle to e-scooter interactions are analyzed. The variables pertaining to the same are also discussed in this paper

Network of European Research Infrastructures for Earthquake Risk Assessment and Mitigation(NERA)

The overall aim of NERA is to achieve a measurable improvement and a long-term impact in the assessment and reduction of the vulnerability of constructions and citizens to earthquakes. NERA will integrate the key research infrastructures in Europe to monitor earthquakes and assess their hazard and risk, and will combine expertise in observational and strong-motion seismology, modeling, geotechnical and earthquake engineering to develop activities to improve the use of infrastructures and facilitate the access to data. NERA will ensure the provision of high-quality services, including access to earthquake data and parameters and to hazard and risk products and tools. NERA will coordinate with other EC projects (SHARE, SYNER-G) a comprehensive dissemination effort. NERA will contribute to the OECD GEM program and to the EPOS ESFRI infrastructure.EU, Funded under :FP7-INFRASTRUCTURES-2010-

RISK ASSESSMENT AND MITIGATION OF TELECOM EQUIPMENT UNDER FREE AIR COOLING CONDITIONS

In recent years, about 40% of the total energy is devoted to the cooling infrastructures in data centers. One way to save energy is free air cooling (FAC), which utilizes the outside air as the primary cooling medium, instead of air conditioning, to reduce the energy consumption to cool the data centers. Despite the energy saving, the implementation of free air cooling will change the operating environment, which may adversely affect the performance and reliability of telecom equipment. This thesis reviews the challenges and risks posed by free air cooling. The increased temperature, uncontrolled humidity, and possible contamination may cause some failure mechanisms, e.g., Conductive anodic filament (CAF) and corrosion, to be more active. If the local temperatures of some hot spots go beyond their recommended operating conditions (RoC), the performances of the equipment may be affected. In this thesis, a methodology is proposed to identify the impact of free air cooling on telecom equipment performance. It uses the performance variations under traditional air condition (A/C) to create a baseline, and compares the performance variation under variable temperature and humidity representing FAC with the baseline. This method can help data centers determine an appropriate operating environment based on the service requirements, when FAC is implemented. In addition, a statics-based approach is also developed to identify the appropriate metric for the performance variations comparison. It is the first study focusing on the impact of FAC on the telecom equipment performance. This thesis also proposes a multi-stage (design, test, and operation) approach to mitigate the reliability risks of telecom equipment under free air cooling conditions. Specifically, a prognostics-based approach is proposed to mitigate the reliability risks at operation stage, and a case study is presented to show the implementation process. This approach needn't interrupt data center services and doesn't consume additional useful life of telecom equipment. It allows the implementation of FAC in data centers which were not originally designed for this cooling method

Concrete Box Beam Risk Assessment and Mitigation: Volume 1—Evolution and Performance

Adjacent box beam bridges have a history of poor long-term performance including premature deterioration and failures. Leaking joints between box beams allow chloride-laden water to migrate through the superstructure and initiate corrosion. The nature of this deterioration leads to uncertainty of the extent and effect of deterioration on structural behavior. Due to limitations in previous research and understanding of the strength of deteriorated box beam bridges, conservative assumptions are made for the assessment and load rating of these bridges. Furthermore, the design of new box beam bridges, which can offer an efficient and economical solution, is often discouraged due to poor past performance. The objective of this research is to develop recommendations for inspection, load-rating, and design of adjacent box beam bridges. The research is presented in two volumes. Volume 1 focuses on the evolution of box beam design in Indiana to understand the lack of performance and durability. The Indiana Department of Transportation (INDOT) standards and bridge design manuals were reviewed to track the historical development of box beam bridges in the State. Two timelines were produced tracking important updates to box beam design. Adjacent box beam bridges within INDOT’s bridge database were also analyzed. Superstructure ratings were compared with bridge age as well as bridge characteristics to highlight possible causes for deterioration. Analyzing the INDOT inventory, data shows that the condition of adjacent box beam bridges may be affected by location, type of wearing surface, and the use of deck membranes. Six bridges were then inspected to identify common deficiencies and specific problems. Exterior beams and beams within the wheel load path tend to have higher levels of deterioration. Furthermore, leaking joints between beams leads to corrosion of reinforcement, ultimately resulting in spalling, fracture of prestressing strands, and loss of structural capacity. Volume 2 focuses on evaluating the capacity of deteriorated adjacent box beams, the development of improved load rating procedures, and new box beam design. Through a series of bridge inspections, deteriorated box beams were identified and acquired for experimental testing. The extent of corrosion was determined through visual inspection, non-destructive evaluation, and destructive evaluation. Non-destructive tests (NDT) included the use of connectionless electrical pulse response analysis (CEPRA), ground penetrating radar (GPR), and half-cell potentials. Deteriorated capacity was determined through structural testing, and an analysis procedure was developed to estimate deteriorated behavior. A rehabilitation procedure was also developed to restore load transfer of adjacent beams in cases where shear key failures are suspected. Based on the understanding of deterioration developed through study of deteriorated adjacent box beam bridges, improved inspection and load rating procedures are provided along with design recommendations for the next generation of box beam bridges

Risk assessment and mitigation of the presence of Nitrosamine impurities in medicines

Tese de mestrado, Engenharia Farmacêutica, 2021, Universidade de Lisboa, Faculdade de Farmácia.N-nitrosaminas, também referidas como nitrosaminas, são classificadas como agentes provavelmente ou possivelmente cancerígenos para os seres humanos, pertencem ao grupo dos compostos N-nitroso, que já demonstraram ser carcinogénicos, mutagénicos e teratogénicos em várias espécies de animais, e são considerados parte do cohort of concern pela Conferência Internacional de Harmonização dos Requisitos Técnicos para os Medicamentos para Uso Humano (ICH). O ser humano está diariamente exposto a várias fontes de nitrosaminas, sendo que estas podem ocorrer, por exemplo, em vários alimentos, como peixe e carne curados, e bebidas alcoólicas; na água potável; no ar; em cosméticos; em produtos de borracha, como chupetas e tetinas; e no fumo de tabaco, sendo esta última a maior fonte de exposição exógena a esta classe de contaminantes. Adicionalmente, estes compostos podem ainda ser formados no organismo, maioritariamente no estômago, e é muito provável que a formação endógena seja a maior fonte de exposição humana. Apesar da ampla distribuição destes contaminantes, a sua presença não era esperada em medicamentos até junho de 2018. Nessa altura as autoridades europeias identificaram a presença da nitrosamina N-nitrosodimetilamina (NDMA) na substância ativa valsartan. Subsequentemente outras nitrosaminas foram também identificadas em lotes de medicamentos valsartan e outros medicamentos da família sartan foram também implicados, levando a recolhas de mercado dos lotes afetados em tudo o mundo. Foi desencadeada uma avaliação do impacto da contaminação com nitrosaminas no balanço risco-benefício destes medicamentos, que estimou que o potencial excesso de risco de cancro seria muito baixo nos níveis em que estas impurezas foram encontradas, concluindo, portanto, que o risco associado à paragem do tratamento seria superior. Até ao momento, estas impurezas foram detetadas também em lotes das seguintes substâncias ativas (e/ou produto acabado) não pertencentes à família sartan: pioglitazona, ranitidina, metformina e rifampicina. De uma forma geral, a formação de nitrosaminas resulta da combinação de aminas nitrosáveis e nitrito ou outros agentes nitrosantes, usualmente na presença de ácido. No entanto, estas impurezas podem também ser introduzidas por contaminação resultante de outras fontes, como por exemplo do uso de equipamento com uma limpeza deficiente e/ou de solventes reciclados. Neste contexto, como medida de precaução, em setembro de 2019 foi solicitado aos titulares de autorizações de introdução no mercado de todos os medicamentos contendo substâncias ativas sintetizadas quimicamente, que efetuassem uma revisão aos seus medicamentos no sentido de avaliar o risco de nitrosaminas poderem estar presentes nos seus produtos, testar todos os medicamentos com potencial risco e implementar medidas de mitigação apropriadas. O objetivo deste projeto prende-se com a primeira parte desse pedido, pretendendo propor uma metodologia que permita à empresa Generis Farmacêutica, S.A., identificar as substâncias ativas e respetivos produtos acabados em risco de formação ou contaminação com nitrosaminas. O desenvolvimento dessa metodologia começou com uma revisão de literatura para identificar as possíveis causas para a presença destas impurezas em medicamentos, que foram de seguida organizadas em três grupos através da construção de um diagrama espinha de peixe: substância ativa, excipientes e produto acabado. Os seguintes fatores foram considerados na avaliação da substância ativa e dos excipientes: presença de precursores de nitrosaminas e condições do processo (com foco no pH e temperatura); equipamento utilizado no processo (uso dedicado ou multipropósito e composição dos agentes de limpeza); uso de solventes ou outros materiais recuperados/reciclados e transporte de solventes “frescos”; uso de matérias-primas, materiais de partida e intermediários contaminados; qualidade da água utilizada no processo (presença de nitritos, nitratos e nitrosaminas); material de embalagem; e no caso da substância ativa foi ainda averiguada a possibilidade de existência processos de degradação que levassem à formação de nitrosaminas ou dos seus precursores durante o prazo de validade. No caso do produto acabado foram considerados alguns fatores também considerados para as avaliações dos outros dois grupos, nomeadamente o equipamento e a qualidade da água utilizados no processo; o material de embalagem utilizado para o produto em bulk e na embalagem primária do produto acabado; e foi também averiguada a possibilidade de existência de processos de degradação do medicamento que resultem na formação de nitrosaminas potencialmente durante o seu armazenamento. Além destes, foi ainda considerada a formulação (possíveis interações entre a substância ativa e os excipientes, em conjunto com a possibilidade do uso de matérias contaminadas com nitrosaminas ou com os seus precursores) juntamente com as condições de processo. De seguida foi aplicada a ferramenta de avaliação de risco recomendada pela Agência Europeia do Medicamento (EMA na sigla inglesa), a FMEA. Para tal, foram sugeridos vários níveis de probabilidade de ocorrência destas impurezas na substância ativa, excipientes, ou produto acabado, considerando situações hipotéticas para cada uma das possíveis causas identificadas em cada um desses grupos. Vários níveis foram também sugeridos para pontuar o parâmetro da detetabilidade, tendo em conta a existência de métodos analíticos capazes de detetar estas impurezas caso existisse risco da sua presença. Foi também proposta uma equação para estimar a severidade (impacto) que a presença destas impurezas teria no doente do produto em avaliação, considerando (1) a máxima dose diária do medicamento; (2) a duração do tratamento; (3) a indicação terapêutica que incluía o público ao qual se destina o medicamento e o local de ação (ação local ou sistémica); e (4) o número de pessoas tratadas. Foi atribuída uma importância superior aos três primeiros fatores (30%) pelas seguintes razões: é sabido que o processo de carcinogénese destes compostos envolve a formação de aductos de DNA, havendo já casos documentados do aumento desta com a dose de nitrosamina, e que a capacidade das enzimas que reparam o DNA é limitada; além disso baseado em estudos animais foi apontado que fetos, bebés e crianças podem apresentar um risco superior de alterações mutagénicas decorrentes da exposição a nitrosaminas. A restante percentagem (10%) foi atribuída ao último fator. A multiplicação das pontuações de severidade, probabilidade e detetabilidade permite obter o valor de RPN, que será tanto mais alto quanto maior for o risco associado à causa em estudo, e de forma a possibilitar a classificação do risco os seguintes limites foram assumidos: risco baixo - RPN ≤ 11; risco médio - 12 ≤ RPN ≤ 26; risco alto - RPN ≥ 27. A estratégia para estimar o risco global da presença de nitrosaminas num dado medicamento foi delineada durante a avaliação do primeiro medicamento em estudo e foi depois aplicada a um segundo medicamento. O primeiro medicamento em estudo foi o Losartan Generis 50mg/100 mg, como tal, foi recolhida toda a informação necessária para pontuar a probabilidade de ocorrência de nitrosaminas na substância ativa losartan de potássio, em cada um dos excipientes e no produto acabado para cada uma das possíveis causas apontadas em cada um desses grupos; e para pontuar também os parâmetros de severidade e detetabilidade. Seguidamente, com os valores de probabilidade, severidade e detetabilidade obtidos calculou-se o RPN para cada uma das causas em estudo. De forma a obter a classificação global do risco foram atribuídas diferentes ponderações a cada uma das causas em avaliação de acordo com a sua importância/contribuição estimada para o risco global da presença destas impurezas em cada um dos grupos em estudo. Foi de seguida proposto que a pior classificação obtida entre a substância ativa, os excipientes e o produto acabado fosse assumida como a classificação global do risco da presença de nitrosaminas no medicamento. Com esta estratégia, foi obtido um valor final de RPN para o medicamento Losartan Generis de 8, o que de acordo com os limites referidos acima VI corresponde a um risco baixo. No entanto, importa referir que esse nível de risco foi obtido apenas após o fabricante da substância ativa ter implementado medidas de mitigação que levaram a uma revisão do nível de risco inicialmente elevado. Seguindo o mesmo racional para o segundo medicamento em estudo, a Ranitidina Generis 150mg/300mg, o valor final de RPN obtido foi 33, o que corresponde a um risco elevado. Até ao momento ainda não foi possível rever o nível de risco obtido para este medicamento, dado que ainda não foram identificadas medidas de mitigação apropriadas. Os resultados obtidos para os medicamentos Losartan Generis e Ranitidina Generis estão em concordância com os resultados das respostas regulatórias em ambos os casos. No caso do primeiro medicamento, inicialmente o CEP da substância ativa foi suspenso com base na avaliação do processo de fabrico que identificou potencial para a formação de nitrosaminas. No entanto, este foi restaurado após o produtor da substância ativa ter investigado as possíveis causas para a formação destas impurezas e ter implementado controlos de rotina adicionais. Já no caso da ranitidina, todos os medicamentos que contêm esta substância ativa foram suspensos da União Europeia. Assim sendo, acredita-se que a metodologia proposta possa ser efetivamente aplicada a outros medicamentos.N-nitrosamines (or nitrosamines) are probable or possible human carcinogens to which man can be exposed from several known sources, such as food, drinking water, tobacco smoke and cosmetic products. However, until mid-2018 their presence in medicinal products was unexpected. These impurities were first detected in the valsartan active pharmaceutical ingredient (API) and subsequently other sartan medicines were also implicated. Meanwhile, these impurities have also been detected in a few non-sartan APIs and/or medicinal products. The regulatory response to the nitrosamines issue included a request to all marketing authorization holders (MAHs) for human medicinal products containing chemically synthesised active pharmaceutical ingredients to evaluate the risk of nitrosamines being present in their products and to take appropriate risk mitigation measures. The aim of the present project is inline with the first part of that request and intends to propose a methodology to support Generis Farmacêutica, S.A., in the identification of APIs and drug products at risk of nitrosamine formation or (cross-)contamination. The proposed methodology encompassed a) the construction of a fishbone diagram, to identify and organize the possible sources of nitrosamines in medicines, taking into consideration the information gathered from a literature review, and b) the use of the risk assessment tool Failure Mode Effects Analysis (FMEA) to determine the risk of finding nitrosamine impurities in medicines. An equation was suggested to estimate the severity (impact) that the presence of nitrosamine impurities in the product under evaluation would have on the patient for which it was intended. Different probabilities of nitrosamine formation or contamination were proposed for each of the possible causes identified and several levels of detectability were also proposed according to the analytical capacity to detect these impurities. Thus, individual risk classifications could then be obtained for each of the causes under evaluation. In order to obtain a global risk classification, different impact factors were attributed to each of the pointed out possible causes according to their estimated importance in the global risk. This process was developed while evaluating the medicine Losartan Generis 50mg/100 mg, which was initially considered as at high risk of nitrosamines presence and was then revised to a low risk following the implementation of mitigation measures. Then, it was applied to the medicine Ranitidina Generis 150/300mg, for which a high risk was obtained and up to date no efficient measures were identified, therefore, it was not possible to revise the risk. As the obtained results were in line with the regulatory responses to both cases (restore the certificate of suitability to the monographs of the European Pharmacopoeia - CEP-, and suspension from the European Union, respectively), it is believed that the proposed methodology can be effectively applied to other medicinal products.Com o patrocínio da Generis Farmacêutica, S.A