RESUMO
Since its introduction in December of 2019, SARS-CoV-2, the virus that causes COVID-19 disease, has rapidly spread across the world. Whilst vaccines are being rolled out, non-pharmaceutical interventions remain the most important tools for mitigating the spread of SARS-CoV-2. Quantifying the impact of these measures as well as determining what settings are prone to instigating (super)spreading events is important for informed and safe reopening of spaces and the targeting of interventions. Mathematical models can help decipher the complex interactions that underlie virus transmission. Currently, most mathematical models developed during the COVID-19 epidemic evaluate interventions at national or subnational levels. Smaller scales of transmission, such as at the level of indoor spaces, have received less attention, despite the central role they play in both transmission and control. Models that do act on this scale use simplified descriptions of human behavior, impeding a valid quantitative analysis of the impact of interventions on transmission in indoor spaces, particularly those that aim for physical distancing. To more accurately predict the transmission of SARS-CoV-2 through a pedestrian environment, we introduce a model that links pedestrian movement and choice dynamics with SARS-CoV-2 spreading models. The objective of this paper is to investigate the spread of SARS-CoV-2 in indoor spaces as it arises from human interactions and assess the relative impact of non-pharmaceutical interventions thereon. We developed a world-wide unique combined Pedestrian Dynamics - Virus Spread model (PeDViS model), which combines insights from pedestrian modelling, epidemiology, and IT-design. In particular, an expert-driven activity assignment model is coupled with the microscopic simulation model (Nomad) and a virus spread model (QVEmod). We first describe the non-linear relationships between the risks of exposure to the virus and the duration, distance, and context of human interactions. We compared virus exposure relative to a benchmark contact (1.5meters for 15 minutes): a threshold often used by public health agencies to determine at risk contacts. We discuss circumstances under which individuals that adhere to common distancing measures may nevertheless be at risk. Specifically, we illustrate the stark increase in exposure at shorter distances, as well as longer contact durations. These risks increase when the infected individual was present in the space before the interaction occurred, as a result of buildup of virus in the environment. The latter is particularly true in poorly ventilated spaces and highlights the importance of good ventilation to prevent potential virus exposure through indirect transmission routes. Combining intervention tools that target different routes of transmission can aid in accumulating impact. We use face masks as an example, which are particularly effective at reducing virus spread that is not affected by ventilation. We then demonstrate the use of PeDViS using a simple restaurant case study, focussing on transmission between guests. In this setting the exposure risk to individuals that are not seated at the same table is limited, but guests seated at nearby tables are estimated to experience exposure risks that surpass that of the benchmark contact. These risks are larger in low ventilation scenarios. Lastly, we illustrate that the impact of intervention measures on the number of new infections heavily depends on the relative efficiency of the direct and indirect transmission routes considered. This uncertainty should be considered when assessing the risks of transmission upon different types of human interactions in indoor spaces. The PeDViS case study shows the multi-dimensionality of SARS-CoV-2 that emerges from the interplay of human behaviour and the spread of respiratory viruses in indoor spaces. A modelling strategy that incorporates this in risk assessments can be an important tool to inform policy makers and citizens. It can empower them to make better design and policy decisions pertaining to the most effective use of measures to limit the spread of SARS-CoV-2 and safely open up indoor spaces.
RESUMO
Radiotherapy is one of the most common treatments for oral cancer. However, in the clinic, recurrence and metastasis of oral cancer occur after radiotherapy, and the underlying mechanism remains unclear. Cancer stem cells (CSCs), considered the "seeds" of cancer, have been confirmed to be in a quiescent state in most established tumours, with their innate radioresistance helping them survive more easily when exposed to radiation than differentiated cancer cells. There is increasing evidence that CSCs play an important role in recurrence and metastasis post-radiotherapy in many cancers. However, little is known about how oral CSCs cause tumour recurrence and metastasis post-radiotherapy. In this review article, we will first summarise methods for the identification of oral CSCs and then focus on the characteristics of a CSC subpopulation induced by radiation, hereafter referred to as "awakened" CSCs, to highlight their response to radiotherapy and potential role in tumour recurrence and metastasis post-radiotherapy as well as potential therapeutics targeting CSCs. In addition, we explore potential therapeutic strategies targeting these "awakened" CSCs to solve the serious clinical challenges of recurrence and metastasis in oral cancer after radiotherapy.
