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The United States Veterans Affairs (VA) Health Care System has a strong history of conducting impactful oncology randomized clinical trials (RCTs). We developed a phase II/III RCT to test the use of metastasis-directed therapy in Veterans with oligometastatic prostate cancer (OMPC)—the first VA RCT in OMPC that leverages novel imaging and advanced radiotherapy techniques. To accomplish this, we developed a clinical trial network to conduct the study. In this manuscript, we describe several challenges we encountered in study development/conduct and our strategies to address them, with the goal of helping investigators establish robust study networks to conduct clinical trials. In the study start-up, we encountered challenges in timely site activation, and leveraged project management to maximize efficiency. Additionally, there were several changes in the clinical paradigms in imaging and treatment that led to protocol amendments to ensure maximum equipoise, recruitment, and impact of the study. Specifically, we amended the trial to add de novo OMPC patients (from initially only recurrent OMPC) and expanded the study to allow up to 10 metastases (from initially five). Finally, in order to maintain local study team engagement, we developed initiatives to maximize collaboration and add value to the overall clinical program through study participation.

Rapid population growth, urbanization and high-intensity human activities cause a multitude of extremely serious environmental problems all over the world [...]

Alterations in metabolism following radiotherapy affect therapeutic efficacy, although the mechanism underlying such alterations is unclear. A new imaging technique—named dynamic nuclear polarization (DNP) carbon-13 magnetic resonance imaging (MRI)—probes the glycolytic flux in a real-time, dynamic manner. The [1-13C]pyruvate is transported by the monocarboxylate transporter (MCT) into cells and converted into [1-13C]lactate by lactate dehydrogenase (LDH). To capture the early glycolytic alterations in the irradiated cancer and immune cells, we designed a preliminary DNP 13C-MRI study by using hyperpolarized [1-13C]pyruvate to study human FaDu squamous carcinoma cells, HMC3 microglial cells, and THP-1 monocytes before and after irradiation. The pyruvate-to-lactate conversion rate (kPL [Pyr.]) calculated by kinetic modeling was used to evaluate the metabolic alterations. Western blotting was performed to assess the expressions of LDHA, LDHB, MCT1, and MCT4 proteins. Following irradiation, the pyruvate-to-lactate conversion rates on DNP 13C-MRI were significantly decreased in the FaDu and the HMC3 cells but increased in the THP-1 cells. Western blot analysis confirmed the similar trends in LDHA and LDHB expression levels. In conclusion, DNP 13C-MRI non-invasively captured the different glycolytic alterations among cancer and immune systems in response to irradiation, implying its potential for clinical use in the future.

Recent surface-water and flash floods have caused millions of pounds worth of damage in the UK. These events form rapidly and are difficult to predict due to their short-lived and localised nature. The interdisciplinary Flooding From Intense Rainfall (FFIR) programme investigated the feasibility of enhancing the integration of an end-to-end forecasting system for flash and surface-water floods to help increase the lead time for warnings for these events. Here we propose developments to the integration of an operational end-to-end forecasting system based on the findings of the FFIR programme. The suggested developments include methods to improve radar-derived rainfall rates and understanding of the uncertainty in the position of intense rainfall in weather forecasts; the addition of hydraulic modelling components; and novel education techniques to help lead to effective dissemination of flood warnings. We make recommendations for future advances such as research into the propagation of uncertainty throughout the forecast chain. We further propose the creation of closer bonds to the end users to allow for an improved, integrated, end-to-end forecasting system that is easily accessible for users and end users alike, and will ultimately help mitigate the impacts of flooding from intense rainfall by informed and timely action.

Flood prevention in mixed urban–rural environments has become a greater concern due to climate change. It is a complex task requiring both efficient management of resources and the involvement of multiple stakeholders from diverse backgrounds. As Serious Games (games used for purposes other than mere entertainment) have emerged as an effective means of engaging stakeholders, this work proposes a new Serious Game applied to flood mitigation in the village of Millbrook in the UK. Results show that the game has both an informative and a transformative effect (statistical significance levels from 0.01 to 0.05), improving participants’ understanding of the problem, and helping them to find a new and improved approach to flood risk management in Millbrook, with the potential to improve resilience significantly. Furthermore, the game successfully transformed participants into “citizen scientists” in the purest sense of the term—it led them to use inductive reasoning from data produced by the game to correctly confirm or reject hypotheses and resulted in more than 70% of the participants revising their initial assumptions. Interestingly, the game instigated the formation of new local partnerships and helped to prioritize the discussion of natural flood management measures in Millbrook Parish Council meetings.

Impacts from floods in urban areas can be diverse and wide ranging. These can include the loss of human life, infrastructure and property damages, as well as other kinds of nuisance and inconvenience to urban life. Hence, the ability to identify and quantify wider ranging effects from floods is of the utmost importance to urban flood managers and infrastructure operators. The present work provides a contribution in this direction and describes a methodological framework for analysing cascading effects from floods that has been applied for the Sukhumvit area in Bangkok (Thailand). It demonstrates that the effects from floods can be much broader in their reach and magnitude than the sole impacts incurred from direct and immediate losses. In Sukhumvit, these include loss of critical services, assets and goods, traffic congestion and delays in transportation, loss of business and income, disturbances and discomfort to the residents, and all these can be traced with the careful analysis of cascading effects. The present work explored the use of different visualization options to present the findings. These include a casual loop diagram, a HAZUR resilience map, a tree diagram and GIS maps.