Suchergebnisse

Abstract
Purpose
The purpose of this article was to highlight current and future trends in radiobiology in an effort to move hadron therapy forward through the application of new knowledge in DNA damage and subsequent response to heavy ion radiotherapy, immune oncology and the interconnection between.

Methods
The subject matter begins with a description of the role of radiation in eliciting either an immunogenic or tolerogenic response to radiation exposure. The role of fragmented DNA in an immunogenic response is described, followed by the definitive role that DNA damage and subsequent repair, or not, of complex DNA damage after hadron exposure plays in the survival response of hadron irradiated cells.

Results
The process by which ionizing radiation elicits an immunogenic rather than tolerogenic response is becoming clearer. The timing of fractionated radiotherapy when combined with an immune checkpoint inhibitor is not clear and may be tumor site specific. Furthermore, whether hadron therapy is more effective at generating a durable immunogenic response is unknown.

Conclusions
Cytosolic DNA plays a significant role in eliciting an innate immune response with the likelihood that hadron therapy would generate complex DNA damage that because it is less likely to be repaired, is more likely to become cytosolic DNA, and more likely to activate an immunogenic response. Lastly, DNA repair pathway choice appears to be a credible bio-indicator for hadron therapy selection as well identify druggable targets to enhance hadron therapy.

Non-compliance regularly negates the effectiveness of marine protected areas (MPAs) worldwide. Understanding and addressing non-compliance is critical given continued efforts to establish MPAs to meet international milestones (e.g., Aichi targets). We conducted a literature review and meta-analysis to address five key questions and research gaps for MPAs: 1) how is non-compliance best measured? 2) what are common drivers of non-compliance? 3) what is the overall prevalence of non-compliance? 4) how frequently is ecological failure of MPAs attributed to non-compliance? and 5) are there measurable management impacts on regulated fishing in MPAs (i.e., effective reduction of fishing)? We found 151 papers that had some focus on non-compliant resource extraction in MPAs and 96 that quantified it. Insufficient enforcement was the most cited driver of non-compliance, followed by several socio-economic drivers including lack of awareness, livelihood/economic gain, social norms, and ineffective governance. Prohibited fishing in MPAs was often reduced compared to outside areas, as shown by our meta-analysis. However, we found frequent reports and measures of non-compliance globally, and many cases of failed ecological performance attributed primarily to non-compliance (57% of 67 relevant studies). Overall, our synthesis demonstrates that non-compliance continues to be a prevalent issue for MPAs. Reducing non-compliance and ensuring effective MPAs will rely on continuous evaluation of non-compliance to inform adaptive management, as well as addressing the complex, interrelated drivers that arise throughout MPA planning, establishment, and management.