In Vivo Microbeam Radiation Therapy at a Conventional Small Animal Irradiator.

Microbeam radiation therapy (MRT) is a still pre-clinical form of spatially fractionated radiotherapy, which uses an array of micrometer-wide, planar beams of X-ray radiation. The dose modulation in MRT has proven effective in the treatment of tumors while being well tolerated by normal tissue. Research on understanding the underlying biological mechanisms mostly requires large third-generation synchrotrons. In this study, we aimed to develop a preclinical treatment environment that would allow MRT independent of synchrotrons. We built a compact microbeam setup for pre-clinical experiments within a small animal irradiator and present in vivo MRT application, including treatment planning, dosimetry, and animal positioning. The brain of an immobilized mouse was treated with MRT, excised, and immunohistochemically stained against γH2AX for DNA double-strand breaks. We developed a comprehensive treatment planning system by adjusting an existing dose calculation algorithm to our setup and attaching it to the open-source software 3D-Slicer. Predicted doses in treatment planning agreed within 10% with film dosimetry readings. We demonstrated the feasibility of MRT exposures in vivo at a compact source and showed that the microbeam pattern is observable in histological sections of a mouse brain. The platform developed in this study will be used for pre-clinical research of MRT.

Proton-FLASH: effects of ultra-high dose rate irradiation on an in-vivo mouse ear model.

FLASH-radiotherapy may provide significant sparing of healthy tissue through ultra-high dose rates in protons, electrons, and x-rays while maintaining the tumor control. Key factors for the FLASH effect might be oxygen depletion, the immune system, and the irradiated blood volume, but none could be fully confirmed yet. Therefore, further investigations are necessary. We investigated the protective (tissue sparing) effect of FLASH in proton treatment using an in-vivo mouse ear model. The right ears of Balb/c mice were irradiated with 20 MeV protons at the ion microprobe SNAKE in Garching near Munich by using three dose rates (Conv = 0.06 Gy/s, Flash9 = 9.3 Gy/s and Flash930 = 930 Gy/s) at a total dose of 23 Gy or 33 Gy. The ear thickness, desquamation, and erythema combined in an inflammation score were measured for 180 days. The cytokines TGF-ß1, TNF-α, IL1α, and IL1ß were analyzed in the blood sampled in the first 4 weeks and at termination day. No differences in inflammation reactions were visible in the 23 Gy group for the different dose rates. In the 33 Gy group, the ear swelling and the inflammation score for Flash9 was reduced by (57 ± 12) % and (67 ± 17) % and for Flash930 by (40 ± 13) % and (50 ± 17) % compared to the Conv dose rate. No changes in the cytokines in the blood could be measured. However, an estimation of the irradiated blood volume demonstrates, that 100-times more blood is irradiated when using Conv compared to using Flash9 or Flash930. This indicates that blood might play a role in the underlying mechanisms in the protective effect of FLASH.

How exercises help US communities meet the challenge of climate change: The FEMA National Exercise Division's innovative exercise tools and resources.

The US Federal Emergency Management Agency (FEMA) National Exercise Division (NED) leads the nation in validating the capabilities of the whole community in support of the National Preparedness System. In response to the increased threat of climate change, the NED has developed new resources to help communities increase preparedness for severe weather and natural disasters in the long term. This paper provides an overview of two such resources to help communities identify and prepare for climate-related events: the Long-Term Community Resilience Exercise Resource Guide (ERG) and the Climate Adaptation Exercise Series (CAES). These resources help communities develop and conduct exercises to increase their climate literacy, develop climate adaptation and mitigation plans, and leverage data on future climate conditions to inform decision-making. Exercises provide an opportunity for communities to build resilience by discussing and better understanding climate change and to plan for, adapt to, and mitigate the associated risks and hazards. The ERG provides guidance, tools and resources, and the CAES provides a consistent framework that FEMA regions can tailor to address unique, region-specific climate concerns. The results collected from these exercises, in turn, identify strengths to leverage and areas to improve, informing plans of action for a path forward for the next 20, 30 and 50 years.

The effect of adjuvants added to local anaesthetics for single-injection upper extremity peripheral regional anaesthesia: A systematic review with network meta-analysis of randomised trials.

BACKGROUND: Peripheral regional anaesthesia is frequently used for upper extremity surgery. To prolong the duration of analgesia, adjuvants can be added to single-injection local anaesthetics. Despite attempts to compare several adjuvants in pairwise meta-analyses, a comprehensive comparison is still missing. OBJECTIVE: The objective of this network meta-analysis was to determine the effectiveness of adjuvants in upper extremity peripheral nerve blocks. DESIGN: A systematic review of randomised controlled trials with network meta-analyses. DATA SOURCES: A literature search in Embase, CENTRAL, MEDLINE and Web of Science was performed up to March 2023. ELIGIBILITY CRITERIA: Randomised trials comparing different adjuvants injected perineurally in peripheral upper extremity nerve blocks were eligible. Frequentist network meta-analysis was conducted using a random effects model with physiological saline as the comparator. The primary endpoint was the ratio of means (ROM) of the duration of analgesia. RESULTS: The review included 242 randomised controlled trials with a total of 17 391 patients. Twenty-eight adjuvants were compared in the largest networks. Most network estimations consisted of a high proportion of direct evidence. Fourteen adjuvants increased the duration of analgesia significantly by the following factors, ROM [95% confidence interval (CI)]: dexamethasone 1.95 (1.79 to 2.13), buprenorphine 1.83 (1.51 to 2.24), butorphanol 1.84 (1.41 to 2.39), potassium chloride 1.89 (1.15 to 3.11), dexmedetomidine 1.70 (1.59 to 1.81), sufentanil 1.70 (1.27 to 2.29), ketorolac 1.68 (1.24 to 2.27), midazolam 1.55 (1.24 to 1.94), tramadol 1.52 (1.32 to 1.75), nalbuphine 1.50 (1.30 to 1.72), morphine 1.43 (1.09 to 1.88), magnesium sulfate 1.42 (1.20 to 1.67), clonidine 1.36 (1.24 to 1.50) and fentanyl 1.23 (1.08 to 1.40). Inconsistency in network meta-analysis was substantial. Overall side effect rates were low with all adjuvants. CONCLUSION: The best interventions to prolong the duration of analgesia were dexamethasone, followed by dexmedetomidine, opioids, electrolytes, ketorolac and midazolam. There are general concerns about the quality of underlying studies and the risk of publication bias. TRIAL REGISTRATION: PROSPERO 2018 CRD42018115722.