Z-Pinch Pulsed Plasma Propulsion Technology Development

Fusion-based propulsion can enable fast interplanetary transportation. Magneto-inertial fusion (MIF) is an approach which has been shown to potentially lead to a low cost, small reactor for fusion break even. The Z-Pinch/dense plasma focus method is an MIF concept in which a column of gas is compressed to thermonuclear conditions by an axial current (I approximates 100 MA). Recent advancements in experiments and the theoretical understanding of this concept suggest favorable scaling of fusion power output yield as I(sup 4). This document presents a conceptual design of a Z-Pinch fusion propulsion system and a vehicle for human exploration. The purpose of this study is to apply Z-Pinch fusion principles to the design of a propulsion system for an interplanetary spacecraft. This study took four steps in service of that objective; these steps are identified below. 1. Z-Pinch Modeling and Analysis: There is a wealth of literature characterizing Z-Pinch physics and existing Z-Pinch physics models. In order to be useful in engineering analysis, simplified Z-Pinch fusion thermodynamic models are required to give propulsion engineers the quantity of plasma, plasma temperature, rate of expansion, etc. The study team developed these models in this study. 2. Propulsion Modeling and Analysis: While the Z-Pinch models characterize the fusion process itself, propulsion models calculate the parameters that characterize the propulsion system (thrust, specific impulse, etc.) The study team developed a Z-Pinch propulsion model and used it to determine the best values for pulse rate, amount of propellant per pulse, and mixture ratio of the D-T and liner materials as well as the resulting thrust and specific impulse of the system. 3. Mission Analysis: Several potential missions were studied. Trajectory analysis using data from the propulsion model was used to determine the duration of the propulsion burns, the amount of propellant expended to complete each mission considered. 4. Vehicle Design: To understand the applicability of Z-Pinch propulsion to interplanetary travel, it is necessary to design a concept vehicle that uses it -- the propulsion system significantly impacts the design of the electrical, thermal control, avionics and structural subsystems of a vehicle. The study team developed a conceptual design of an interplanetary vehicle that transports crew and cargo to Mars and back and can be reused for other missions. Several aspects of this vehicle are based on a previous crewed fusion vehicle study -- the Human Outer Planet Exploration (HOPE) Magnetized Target Fusion (MTF) vehicle. Portions of the vehicle design were used outright and others were modified from the MTF design in order to maintain comparability

Design of Z-Pinch and Dense Plasma Focus Powered Vehicles

Z-pinch and Dense Plasma Focus (DPF) are two promising techniques for bringing fusion power to the field of in-space propulsion. A design team comprising of engineers and scientists from UAHuntsville, NASA's George C. Marshall Space Flight Center and the University of Wisconsin developed concept vehicles for a crewed round trip mission to Mars and an interstellar precursor mission. Outlined in this paper are vehicle concepts, complete with conceptual analysis of the mission profile, operations, structural and thermal analysis and power/avionics design. Additionally engineering design of the thruster itself is included. The design efforts adds greatly to the fidelity of estimates for power density (alpha) and overall performance for these thruster concept

Successful treatment of residual pituitary adenoma in persistent acromegaly following localisation by 11C-methionine PET co-registered with MRI.

OBJECTIVE: To determine if functional imaging using 11C-methionine positron emission tomography co-registered with 3D gradient echo MRI (Met-PET/MRI), can identify sites of residual active tumour in treated acromegaly, and discriminate these from post-treatment change, to allow further targeted treatment. DESIGN/METHODS: Twenty-six patients with persistent acromegaly after previous treatment, in whom MRI appearances were considered indeterminate, were referred to our centre for further evaluation over a 4.5-year period. Met-PET/MRI was performed in each case, and findings were used to decide regarding adjunctive therapy. Four patients with clinical and biochemical remission after transsphenoidal surgery (TSS), but in whom residual tumour was suspected on post-operative MRI, were also studied. RESULTS: Met-PET/MRI demonstrated tracer uptake only within the normal gland in the four patients who had achieved complete remission after primary surgery. In contrast, in 26 patients with active acromegaly, Met-PET/MRI localised sites of abnormal tracer uptake in all but one case. Based on these findings, fourteen subjects underwent endoscopic TSS, leading to a marked improvement in (n = 7), or complete resolution of (n = 7), residual acromegaly. One patient received stereotactic radiosurgery and two patients with cavernous sinus invasion were treated with image-guided fractionated radiotherapy, with good disease control. Three subjects await further intervention. Five patients chose to receive adjunctive medical therapy. Only one patient developed additional pituitary deficits after Met-PET/MRI-guided TSS. CONCLUSIONS: In patients with persistent acromegaly after primary therapy, Met-PET/MRI can help identify the site(s) of residual pituitary adenoma when MRI appearances are inconclusive and direct further targeted intervention (surgery or radiotherapy).This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector. OK, ASP, NB, JDP and MG are supported by the NIHR Cambridge Biomedical Research Centre. JDP has received support by an NIHR Senior Investigator award and NIHR brain injury HTC.This is the author accepted manuscript. The final version is available from BioScientifica via https://doi.org/10.1530/EJE-16-063

Origins and functional consequences of somatic mitochondrial DNA mutations in human cancer

Recent sequencing studies have extensively explored the somatic alterations present in the nuclear genomes of cancers. Although mitochondria control energy metabolism and apoptosis, the origins and impact of cancer-associated mutations in mtDNA are unclear. In this study, we analyzed somatic alterations in mtDNA from 1675 tumors. We identified 1907 somatic substitutions, which exhibited dramatic replicative strand bias, predominantly C > T and A > G on the mitochondrial heavy strand. This strand-asymmetric signature differs from those found in nuclear cancer genomes but matches the inferred germline process shaping primate mtDNA sequence content. A number of mtDNA mutations showed considerable heterogeneity across tumor types. Missense mutations were selectively neutral and often gradually drifted towards homoplasmy over time. In contrast, mutations resulting in protein truncation undergo negative selection and were almost exclusively heteroplasmic. Our findings indicate that the endogenous mutational mechanism has far greater impact than any other external mutagens in mitochondria and is fundamentally linked to mtDNA replication

Assessment of neuropsychological function in brain tumor treatment: a comparison of traditional neuropsychological assessment with app-based cognitive screening.

Funder: Guarantors of Brain; doi: http://dx.doi.org/10.13039/501100000627Funder: Cancer Research UKFunder: Junta de Andalucía; doi: http://dx.doi.org/10.13039/501100011011BACKGROUND: Gliomas are typically considered to cause relatively few neurological impairments. However, cognitive difficulties can arise, for example during treatment, with potential detrimental effects on quality of life. Accurate, reproducible, and accessible cognitive assessment is therefore vital in understanding the effects of both tumor and treatments. Our aim is to compare traditional neuropsychological assessment with an app-based cognitive screening tool in patients with glioma before and after surgical resection. Our hypotheses were that cognitive impairments would be apparent, even in a young and high functioning cohort, and that app-based cognitive screening would complement traditional neuropsychological assessment. METHODS: Seventeen patients with diffuse gliomas completed a traditional neuropsychological assessment and an app-based touchscreen tablet assessment pre- and post-operatively. The app assessment was also conducted at 3- and 12-month follow-up. Impairment rates, mean performance, and pre- and post-operative changes were compared using standardized Z-scores. RESULTS: Approximately 2-3 h of traditional assessment indicated an average of 2.88 cognitive impairments per patient, while the 30-min screen indicated 1.18. As might be expected, traditional assessment using multiple items across the difficulty range proved more sensitive than brief screening measures in areas such as memory and attention. However, the capacity of the screening app to capture reaction times enhanced its sensitivity, relative to traditional assessment, in the area of non-verbal function. Where there was overlap between the two assessments, for example digit span tasks, the results were broadly equivalent. CONCLUSIONS: Cognitive impairments were common in this sample and app-based screening complemented traditional neuropsychological assessment. Implications for clinical assessment and follow-up are discussed

A Prospective Study of Longitudinal Risks of Cognitive Deficit for People Undergoing Glioblastoma Surgery Using a Tablet Computer Cognition Testing Battery: Towards Personalized Understanding of Risks to Cognitive Function

Glioblastoma and the surgery to remove it pose high risks to the cognitive function of patients. Little reliable data exist about these risks, especially postoperatively before radiotherapy. We hypothesized that cognitive deficit risks detected before surgery will be exacerbated by surgery in patients with glioblastoma undergoing maximal treatment regimens. We used longitudinal electronic cognitive testing perioperatively to perform a prospective, longitudinal, observational study of 49 participants with glioblastoma undergoing surgery. Before surgery (A1), the participant risk of deficit in 5/6 cognitive domains was increased compared to normative data. Of these, the risks to Attention (OR = 31.19), Memory (OR = 97.38), and Perception (OR = 213.75) were markedly increased. These risks significantly increased in the early period after surgery (A2) when patients were discharged home or seen in the clinic to discuss histology results. For participants tested at 4–6 weeks after surgery (A3) before starting radiotherapy, there was evidence of risk reduction towards A1. The observed risks of cognitive deficit were independent of patient-specific, tumour-specific, and surgery-specific co-variates. These results reveal a timeframe of natural recovery in the first 4–6 weeks after surgery based on personalized deficit profiles for each participant. Future research in this period could investigate personalized rehabilitation tools to aid the recovery process found

A Prospective Study of Longitudinal Risks of Cognitive Deficit for People Undergoing Glioblastoma Surgery Using a Tablet Computer Cognition Testing Battery: Towards Personalized Understanding of Risks to Cognitive Function.

Peer reviewed: TrueFunder: NIHR Brain Injury MedTech Co-operativeGlioblastoma and the surgery to remove it pose high risks to the cognitive function of patients. Little reliable data exist about these risks, especially postoperatively before radiotherapy. We hypothesized that cognitive deficit risks detected before surgery will be exacerbated by surgery in patients with glioblastoma undergoing maximal treatment regimens. We used longitudinal electronic cognitive testing perioperatively to perform a prospective, longitudinal, observational study of 49 participants with glioblastoma undergoing surgery. Before surgery (A1), the participant risk of deficit in 5/6 cognitive domains was increased compared to normative data. Of these, the risks to Attention (OR = 31.19), Memory (OR = 97.38), and Perception (OR = 213.75) were markedly increased. These risks significantly increased in the early period after surgery (A2) when patients were discharged home or seen in the clinic to discuss histology results. For participants tested at 4-6 weeks after surgery (A3) before starting radiotherapy, there was evidence of risk reduction towards A1. The observed risks of cognitive deficit were independent of patient-specific, tumour-specific, and surgery-specific co-variates. These results reveal a timeframe of natural recovery in the first 4-6 weeks after surgery based on personalized deficit profiles for each participant. Future research in this period could investigate personalized rehabilitation tools to aid the recovery process found.Cancer Research UK (RRZB/040 and RRAG/287) Royal College of Surgeons of England (RRAG/093) Medical Research Council (SUAG/049 and G101-400); National Institute for Health Research (NIHR), Career Development Fellowship for this research project (CDF-2018-11-ST2-003)

A Prospective Study of Longitudinal Risks of Cognitive Deficit for People Undergoing Glioblastoma Surgery Using a Tablet Computer Cognition Testing Battery: Towards Personalized Understanding of Risks to Cognitive Function

Glioblastoma and the surgery to remove it pose high risks to the cognitive function of patients. Little reliable data exist about these risks, especially postoperatively before radiotherapy. We hypothesized that cognitive deficit risks detected before surgery will be exacerbated by surgery in patients with glioblastoma undergoing maximal treatment regimens. We used longitudinal electronic cognitive testing perioperatively to perform a prospective, longitudinal, observational study of 49 participants with glioblastoma undergoing surgery. Before surgery (A1), the participant risk of deficit in 5/6 cognitive domains was increased compared to normative data. Of these, the risks to Attention (OR = 31.19), Memory (OR = 97.38), and Perception (OR = 213.75) were markedly increased. These risks significantly increased in the early period after surgery (A2) when patients were discharged home or seen in the clinic to discuss histology results. For participants tested at 4–6 weeks after surgery (A3) before starting radiotherapy, there was evidence of risk reduction towards A1. The observed risks of cognitive deficit were independent of patient-specific, tumour-specific, and surgery-specific co-variates. These results reveal a timeframe of natural recovery in the first 4–6 weeks after surgery based on personalized deficit profiles for each participant. Future research in this period could investigate personalized rehabilitation tools to aid the recovery process found.Cancer Research UK (RRZB/040 and RRAG/287) Royal College of Surgeons of England (RRAG/093) Medical Research Council (SUAG/049 and G101-400); National Institute for Health Research (NIHR), Career Development Fellowship for this research project (CDF-2018-11-ST2-003)