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INTRODUCTION: Despite an increasing aging population, older adults (≥ 65 years) with primary brain tumors (PBTs) are not routinely assessed for geriatric vulnerabilities. Recent reports of geriatric assessment (GA) in patients with glioblastomas demonstrated that GA may serve as a sensitive prognosticator of overall survival. Yet, current practice does not include routine evaluation of geriatric vulnerabilities and the relevance of GA has not been previously evaluated in broader cohorts of PBT patients. The objective of this descriptive study was to assess key GA constructs in adults with PBT dichotomized into older versus younger groups. MATERIALS AND METHODS: A cross-sectional analysis of data collected from 579 participants with PBT recruited between 2016 and 2020, dichotomized into older (≥ 65 years, n = 92) and younger (≤ 64 years, n = 487) from an ongoing observational trial. GA constructs were evaluated using socio-demographic characteristics, Charlson Comorbidity Index (CCI), polypharmacy (>5 daily medications), Karnofsky Performance Status (KPS), Neurologic Function Score (NFS), and patient-reported outcome assessments including general health, functional status, symptom burden and interference, and mood. Descriptive statistics, t-tests, chi-square tests, and Pearson correlations were used to evaluate differences between age groups. RESULTS: Older participants were more likely to have problems with mobility (58% vs. 44%), usual activities (64% vs 50%) and self-care (38% vs 26%) compared to the younger participants (odds ratios [ORs] = 1.3–1.4, ps

Glioblastoma remains incurable despite advances in surgery, radiation, and chemotherapy, underscoring the need for new therapies. The genetic heterogenicity, presence of redundant molecular pathways, and the blood-brain barrier have limited the applicability of molecularly targeted agents. The therapeutic benefit seen with a small subset of patients suggests, however, that patient selection is critical. Recent investigations show that molecularly targeted synthetic lethality is a promising complementary approach. The article provides an overview of the challenges of molecularly targeted therapy in adults with glioblastoma, including current trials and future therapeutic directions.

Despite intensive research, brain tumors are amongst the malignancies with the worst prognosis; therefore, a prompt diagnosis and thoughtful assessment of the disease is required. The resistance of brain tumors to most forms of conventional therapy has led researchers to explore the underlying biology in search of new vulnerabilities and biomarkers. The unique metabolism of brain tumors represents one potential vulnerability and the basis for a system of classification. Profiling this aberrant metabolism requires a method to accurately measure and report differences in metabolite concentrations. Magnetic resonance-based techniques provide a framework for examining tumor tissue and the evolution of disease. Nuclear Magnetic Resonance (NMR) analysis of biofluids collected from patients suffering from brain cancer can provide biological information about disease status. In particular, urine and plasma can serve to monitor the evolution of disease through the changes observed in the metabolic profiles. Moreover, cerebrospinal fluid can be utilized as a direct reporter of cerebral activity since it carries the chemicals exchanged with the brain tissue and the tumor mass. Metabolic reprogramming has recently been included as one of the hallmarks of cancer. Accordingly, the metabolic rewiring experienced by these tumors to sustain rapid growth and proliferation can also serve as a potential therapeutic target. The combination of 13C tracing approaches with the utilization of different NMR spectral modalities has allowed investigations of the upregulation of glycolysis in the aggressive forms of brain tumors, including glioblastomas, and the discovery of the utilization of acetate as an alternative cellular fuel in brain metastasis and gliomas. One of the major contributions of magnetic resonance to the assessment of brain tumors has been the non-invasive determination of 2-hydroxyglutarate (2HG) in tumors harboring a mutation in isocitrate dehydrogenase 1 (IDH1). The mutational status of this enzyme already serves as a key feature in the clinical classification of brain neoplasia in routine clinical practice and pilot studies have established the use of in vivo magnetic resonance spectroscopy (MRS) for monitoring disease progression and treatment response in IDH mutant gliomas. However, the development of bespoke methods for 2HG detection by MRS has been required, and this has prevented the wider implementation of MRS methodology into the clinic. One of the main challenges for improving the management of the disease is to obtain an accurate insight into the response to treatment, so that the patient can be promptly diverted into a new therapy if resistant or maintained on the original therapy if responsive. The implementation of 13C hyperpolarized magnetic resonance spectroscopic imaging (MRSI) has allowed detection of changes in tumor metabolism associated with a treatment, and as such has been revealed as a remarkable tool for monitoring response to therapeutic strategies. In summary, the application of magnetic resonance-based methodologies to the diagnosis and management of brain tumor patients, in addition to its utilization in the investigation of its tumor-associated metabolic rewiring, is helping to unravel the biological basis of malignancies of the central nervous system.

The isocitrate dehydrogenase (IDH1/2) mutations are frequent genetic abnormalities in the majority of WHO grade II/III glioma and secondary GBM. IDH1-mutated (IDH1Mut) glioma exhibits distinctive patterns in cancer biology and metabolism. In the present study, we showed that bone morphogenetic proteins (BMP4) are significantly upregulated in IDH1Mut glioma. Further, we demonstrated that cancer-associated BMP4 is secreted to tumor microenvironment, which enhances the tumor migration and invasion through an autocrine manner. Mechanistically, BMP4 activates its receptor and concomitant SMAD1/5/8 signaling, which potentiates Wnt/β-catenin signaling by enhancing Frizzled receptor expression. LDN-193189, a selective BMP receptor inhibitor, prolonged the overall survival of mice bearing IDH1-mutated intracranial xenografts by limiting BMP/catenin signaling. These findings demonstrate the pivotal role of BMP4 on tumor aggressiveness in IDH1Mut gliomas, suggesting a possible therapeutic strategy for this type of malignancy.

Recognising the importance of clinical outcomes assessments (COAs), the Response Assessment in Neuro-Oncology-Patient Reported Outcome (RANO-PRO) Working Group recommended inclusion of core symptoms and functions in clinical care or research for malignant glioma patients. This study evaluated the association of the recommended symptoms (pain, perceived cognition, seizures, aphasia, symptomatic adverse events) and functions (weakness, walking, work, usual activities) with disease progression in these patients.In this retrospective cohort study, patients with malignant glioma were included from the US National Cancer Institute Neuro-Oncology Branch Natural History Study (NOB-NHS) which follows primary central nervous system tumour patients aged 18 years and older throughout their disease trajectory. The M.D. Anderson Symptom Inventory-Brain Tumor (MDASI-BT), EQ-5D-3L, Karnofsky Performance Status (KPS), and Neurologic Function scores (NFS) were evaluated in relation to disease progression by chi-square tests, independent- and paired-samples t-tests, adjusted for multiple comparisons at first assessment and over time to a second assessment. Radiographic disease progression was determined on the interpretation of the imaging study by a radiologist and neuro-oncologist using standard criteria as part of clinical trial participation or routine standard of care. The priority constructs were evaluated to provide initial evidence of their relevance, relationship to disease status over time, and sensitivity to change in a diverse group of patients with malignant glioma.Seven hundred and sixty-five patients had enrolled into the NOB-NHS between September 1, 2016 and January 31, 2020. Three hundred and thirty-six patients had a diagnosis of a malignant glioma (anaplastic astrocytoma, anaplastic oligodendroglioma, glioblastoma, and gliosarcoma) and were included in the current study. The sample was 64% male (n = 215), 36% female (n = 121), median age of 52 years (IQR = 18.75), 82% White (n = 276), and 65% had tumour recurrence (n = 219). One hundred and fifty-four (46%) had radiographic disease progression. Difficulty remembering, fatigue, and weakness were worse in the group whose imaging was interpreted as radiographic disease progression versus stable disease, as well as the functions of walking, work, activity, and self-care (1.1difference1.8). Patients with disease progression were four times more likely to have a poor KPS (≤80) and worse NFS. Among patients with disease progression at a second assessment (n = 112), all symptoms, except seizures, worsened between first assessment and disease progression and up to 22% of patients (n = 25) reported worsening mobility, self-care, and usual activity; 46% (n = 51) and 35% (n = 30) had worsened KPS and NFS, respectively. On average, 4 symptoms or functions (SD = 3) were reported as moderate-to-severe and 30% (n = 33) and 23% (n = 26) had a change to moderate-to-severe fatigue and walking, respectively, at time of disease progression. Over 7% of patients with worsening (n = 7 of 100) reported every symptom and function as having changed the most severely including seizures with fatigue and activity reported as the top symptom and function, respectively.The identified core symptoms and functions worsened at the time of progression, supporting the relevance and sensitivity of the priority constructs identified by the RANO-PRO Working Group for clinical care and clinical trials for malignant glioma patients.The Natural History Study is supported by Intramural Project 1ZIABC011786-03.

The processing code SPECTRA-PKA produces energy spectra of primary atomic recoil events (or primary knock-on atoms, PKAs) for any material composition exposed to an irradiation spectrum. Such evaluations are vital inputs for simulations aimed at understanding the evolution of damage in irradiated material, which is generated in cascade displacement events initiated by PKAs. These PKA spectra present the full complexity of the input (to SPECTRA-PKA) nuclear data-library evaluations of recoil events. However, the commonly used displacements per atom (dpa) measure, which is an integral measure over all possible recoil events of the displacement damage dose, is still widely used and has many useful applications – as both a comparative and correlative quantity. This paper describes the methodology employed that allows the SPECTRA-PKA code to evaluate dpa rates using the energy-dependent recoil (PKA) cross section data used for the PKA distributions. This avoids the need for integral displacement kerma cross sections and also provides new insight into the relative importance of different reaction channels (and associated different daughter residual and emitted particles) to the total integrated dpa damage dose. Results are presented for Fe, Ni, W, and SS316. Fusion dpa rates are compared to those in fission, highlighting the increased contribution to damage creation in the former from high-energy threshold reactions.

Background Conventional phase I algorithms for finding a phase-2 recommended dose (P2RD) based on toxicity alone is problematic because the maximum tolerated dose (MTD) is not necessarily the optimal dose with the most desirable risk–benefit trade-off. Moreover, the increasingly common practice of treating an expansion cohort at a chosen MTD has undesirable consequences that may not be obvious. Patients and methods We review the phase I–II paradigm and the EffTox design, which utilizes both efficacy and toxicity to choose optimal doses for successive patient cohorts and find the optimal P2RD. We conduct a computer simulation study to compare the performance of the EffTox design with the traditional 3 + 3 design and the continuous reassessment method. Results By accounting for the risk–benefit trade-off, the EffTox phase I–II design overcomes the limitations of conventional toxicity-based phase I designs. Numerical simulations show that the EffTox design has higher probabilities of identifying the optimal dose and treats more patients at the optimal dose. Conclusions Phase I–II designs, such as the EffTox design, provide a coherent and efficient approach to finding the optimal P2RD by explicitly accounting for risk–benefit trade-offs underlying medical decisions.

Simulations of neutron damage under fusion energy conditions must capture the effects of transmutation, both in terms of accurate chemical inventory buildup as well as the physics of the interactions between transmutation elements and irradiation defect clusters. In this work, we integrate neutronics, primary damage calculations, molecular dynamics results, Re transmutation calculations, and stochastic cluster dynamics simulations to study neutron damage in single-crystal tungsten to mimic divertor materials. To gauge the accuracy and validity of the simulations, we first study the material response under experimental conditions at the JOYO fast reactor in Japan and the High Flux Isotope Reactor at Oak Ridge National Laboratory, for which measurements of cluster densities and hardening levels up to 2 dpa exist. We then provide calculations under expected DEMO fusion conditions. Several key mechanisms involving Re atoms and defect clusters are found to govern the accumulation of irradiation damage in each case. We use established correlations to translate damage accumulation into hardening increases and compare our results to the experimental measurements. We find hardening increases in excess of 5000 MPa in all cases, which casts doubts about the integrity of W-based materials under long-term fusion exposure.

Purpose To determine the impact on overall survival with different salvage therapies, including no treatment, reirradiation, systemic therapy, or radiation and systemic therapy, in participants of a phase 3 clinical trial evaluating dose-dense versus standard-dose temozolomide for patients with newly diagnosed glioblastoma. Methods and Materials This analysis of patients from Trial RTOG 0525 investigated the effect of reirradiation or systemic treatment after tumor progression. Survival from first progression was compared between patients receiving no therapy, systemic therapy alone, radiation alone, and both modalities. The Cox proportional hazards model was used to compare the mortality hazard, controlling for potential confounders. Results The analysis included 637 patients who progressed and had information on their management, excluding those who died less than half a month after progression. A total of 267 patients (42%) received neither reirradiation nor systemic treatment at progression, 24 (4%) received radiation alone, 282 (44%) received systemic treatment only, and 64 (10%) received both radiation and systemic therapy. Patients who received no treatment had a median survival of 4.8 months, lower than with radiation treatment alone (8.2 months), systemic therapy alone (10.6 months), and both radiation and systemic therapy (12.2 months). In survival models controlling for potential confounders, those who received radiation alone had modestly better survival (hazard ratio HR 0.74, 95% confidence interval [CI] 0.43-1.28), whereas those who underwent systemic therapy either without (HR 0.42, 95% CI 0.34-0.53) or with radiation therapy (HR 0.44, 95% CI 0.30-0.63) had better survival. There was no significant survival difference between patients who received radiation only and those who received systemic therapy (either with radiation or alone). Conclusions Patients who received no salvage treatment had poorer survival than those who received radiation, chemotherapy, or the combination. However, patient selection for no treatment likely reflects poorer expected prognosis. There was no significant survival difference among those receiving radiation therapy, systemic therapy, or both. Ongoing clinical trials will help define the role of reirradiation after glioblastoma progression.

Predictions of material activation inventories will be a key input to virtually all aspects of the operation, safety and environmental assessment of future fusion nuclear plants. Additionally, the neutron-induced transmutation (change) of material composition (inventory) with time, and the creation and evolution of configurational damage from atomic displacements, require precise quantification because they can lead to significant changes in material properties, and thus influence reactor-component lifetime. A comprehensive scoping study has been performed to quantify the activation, transmutation (depletion and build-up) and immediate damage response under neutron irradiation for all naturally occurring elements from hydrogen to bismuth. The resulting database provides a global picture of the response of a material, covering the majority of nuclear technological space, but focussing specifically on typical conditions expected for a demonstration fusion power plant (DEMO). Results from fusion are compared against typical fission conditions for selected fusion relevant materials, demonstrating that the latter cannot be relied upon to give accurate scalable experimental predictions of material response in a future fusion reactor. Results from different nuclear data libraries are also compared, highlighting the variations and deficiencies., Comment: 14 pages, 9 figures, submission to Fus. Eng. Des. special issue for 3rd joint IAEA-ITER technical meeting on ITER Materials and Technologies

The ITER project aims to demonstrate scientific and technological feasibility of controlled energy production through thermonuclear fusion and the IAEA plays a pro-active role in catalyzing innovation and enhancing the worldwide commitment to fusion. The 3rd Joint IAEA-ITER Technical Meeting on ITER Materials & Technologies, held in November 2015 has been aimed to contribute to the development of a knowledge base of properties, processes and technologies relevant to ITER structural and plasma-facing materials/components. This paper is a summary of the presentations and discussions of the meeting, which was mainly devoted to materials and technologies for ITER, while those relevant beyond, like a DEMO were considered as well within the scope.

The high anisotropy in the thermal conductivity of lithium metatitanate, Li2TiO3, is shown using the classical simulation method of Molecular Dynamics (MD). The thermal conductivity along the z -direction is markedly lower than that in x and y . This characteristic could be exploited in the fabrication of breeder blanket design to favourably adjust the thermal conductivity of Li2TiO3 by ensuring alignment along x or y . This work sets the foundation for investigating the effect of defects on the thermal conductivity of Li2TiO3, as anticipated to be formed during the lifetime of a breeder blanket.

The FISPACT-II inventory simulation platform is a modern computational tool with advanced and unique capabilities. It is sufficiently flexible and efficient to make it an ideal basis around which to perform extensive simulation studies to scope a variety of responses of many materials (elements) to several different neutron irradiation scenarios. This paper briefly presents the typical outputs from these scoping studies, which have been used to compile a suite of nuclear physics materials handbooks, providing a useful and vital resource for material selection and design studies. Several different global responses are extracted from these reports, allowing for comparisons between materials and between different irradiation conditions. A new graphical output format has been developed for the FISPACT-II platform to display these “global summaries”; results for different elements are shown in a periodic table layout, allowing side-by-side comparisons. Several examples of such plots are presented and discussed.

Fispact-II is a code system and library database for modelling activation-transmutation processes, depletion-burn-up, time dependent inventory and radiation damage source terms caused by nuclear reactions and decays. The Fispact-II code, written in object-style Fortran, follows the evolution of material irradiated by neutrons, alphas, gammas, protons, or deuterons, and provides a wide range of derived radiological output quantities to satisfy most needs for nuclear applications. It can be used with any ENDF-compliant group library data for nuclear reactions, particle-induced and spontaneous fission yields, and radioactive decay (including but not limited to TENDL-2015, ENDF/B-VII.1, JEFF-3.2, JENDL-4.0u, CENDL-3.1 processed into fine-group-structure files, GEFY-5.2 and UKDD-16), as well as resolved and unresolved resonance range probability tables for self-shielding corrections and updated radiological hazard indices. The code has many novel features including: extension of the energy range up to 1 GeV; additional neutron physics including self-shielding effects, temperature dependence, thin and thick target yields; pathway analysis; and sensitivity and uncertainty quantification and propagation using full covariance data. The latest ENDF libraries such as TENDL encompass thousands of target isotopes. Nuclear data libraries for Fispact-II are prepared from these using processing codes PREPRO, NJOY and CALENDF. These data include resonance parameters, cross sections with covariances, probability tables in the resonance ranges, PKA spectra, kerma, dpa, gas and radionuclide production and energy-dependent fission yields, supplemented with all 27 decay types. All such data for the five most important incident particles are provided in evaluated data tables. The Fispact-II simulation software is described in detail in this paper, together with the nuclear data libraries. The Fispact-II system also includes several utility programs for code-use optimisation, visualisation and production of secondary radiological quantities. Included in the paper are summaries of results from the suite of verification and validation reports available with the code.

Hematopoietic cells are increasingly recognized as playing key roles in tumor growth and metastatic progression. Although many studies have focused on the functional interaction of hematopoietic cells with tumor cells, few have examined the regulation of hematopoiesis by the hematopoietic stem cell (HSC) niche in the setting of cancer. Hematopoiesis occurs primarily in the bone marrow, and processes including expansion, mobilization, and differentiation of hematopoietic progenitors are tightly regulated by the specialized stem cell niche. Loss of niche components or the ability of stem cells to localize to the stem cell niche relieves HSCs of the restrictions imposed under normal homeostasis. In this review, we discuss how tumor-derived factors and therapeutic interventions disrupt structural and regulatory properties of the stem cell niche, resulting in niche invasion by hematopoietic malignancies, extramedullary hematopoiesis, myeloid skewing by peripheral tissue microenvironments, and lymphopenia. The key regulatory roles played by the bone marrow niche in hematopoiesis has implications for therapy-related toxicity and the successful development of immune-based therapies for cancer.

High temperature, neutron irradiated single crystal tungsten,with a post irradiation composition of W-1.20±0.11at.%Re-0.11±0.05at.%Os0.03±0.01at.%Ta was characterised using a combination of Atom ProbeTomography (APT) and Scanning Tunnelling Electron Microscopy (STEM). APTshowed that within nanoscale clusters of Re/Os, the atomic density wasabove the theoretical limit. Complimentary High Angle Annular Dark Field(HAADF) imaging shows that some clusters contain voids at their centrewhich are leading to APT aberrations and enhancing the atomic density.High resolution Energy Dispersive X-ray (EDX) spectroscopy shows thatvoids are decorated with a shell of rhenium with a small osmium clusterto one side.

Targeting glutamine metabolism in cancer has become increasingly vibrant area of research. Mutant IDH1 (IDH1mut) gliomas are considered good candidates for targeting this pathway because of the contribution of glutamine to their newly acquired function: synthesis of 2-hydroxyglutarate (2HG). Here, we report the adaptability of IDH1mut cells’ metabolism to the inhibition of glutamine/glutamate pathway. The glutaminase inhibitor CB839 showed decreased production of the downstream metabolites of glutamate, including those involved in the TCA cycle and 2HG. However, this effect on metabolism was not extended to viability; rather, our patient-derived IDH1mut cell lines display a metabolic plasticity that allows them to overcome glutaminase inhibition. The major metabolic adaptation involved pathways that can generate glutamate by using alternative substrates from glutamine, such as alanine or aspartate. Indeed, asparagine synthetase was upregulated both in vivo and in vitro revealing a new potential therapeutic target for a combinatory approach with CB839 against IDH1mut gliomas.

Precision oncology has made significant advances, mainly by targeting actionable mutations in cancer driver genes. Aiming to expand treatment opportunities, recent studies have begun to explore the utility of tumor transcriptome to guide patient treatment. Here, we introduce SELECT (synthetic lethality and rescue-mediated precision oncology via the transcriptome), a precision oncology framework harnessing genetic interactions to predict patient response to cancer therapy from the tumor transcriptome. SELECT is tested on a broad collection of 35 published targeted and immunotherapy clinical trials from 10 different cancer types. It is predictive of patients' response in 80% of these clinical trials and in the recent multi-arm WINTHER trial. The predictive signatures and the code are made publicly available for academic use, laying a basis for future prospective clinical studies.

Spectrum unfolding is a key tool used together with diagnostics in the determination of nuclear fields that are associated with a range of nuclear technologies spanning fusion, fission, nuclear medicine and accelerator domains. The underlying process requires a mathematical method for solving the Fredholm integral equation of the first kind. This paper discusses the development, testing and comparison of the modern combined framework of methods for performing neutron spectrum unfolding SPECTRA-UF, which includes the UF_G and UF_M subroutines, based on the underlying mathematics of the GRAVEL and MAXED methods respectively, along with a custom parameterised subroutine, UF_P. We compared the behaviour of each method using a set of synthetic data. We discuss the challenges associated with unfolding fusion spectra, and the behaviour of each subroutine along with the feasibility of using general parameterised spectra as initial a priori spectra. The UF_M, UF_G and UF_P methods showed reasonable agreement where good a priori was supplied and all improved on the a priori spectrum given, but behaved poorly where less accurate a priori was provided, with UF_G showing itself to rely more heavily on the a priori spectrum given. The UF_M subroutine performed most favourably, producing the lowest mean fractional deviation across the majority of spectra. The UF_P was able to represent the fusion peaks and relatively smooth epi-thermal regions, but performed less well where the flux spanned many orders of magnitude. The modelling of the down-scatter component of the fusion peaks was also challenging to reliably model using simple distributions.

Efficient and reliable detection of radiological or nuclear threats is a crucial part of national and international efforts to prevent terrorist activities. Radiation Portal Monitors (RPMs), which are deployed worldwide, are intended to interdict smuggled fissile material by detecting emissions of neutrons and gamma rays. However, considering the range and variety of threat sources, vehicular and shielding scenarios, and that only a small signature is present, it is important that the design of the RPMs allows these signatures to be accurately differentiated from the environmental background. Using Monte-Carlo neutron-transport simulations of a model 3 He detector system we have conducted a parameter study to identify the optimum combination of detector shielding, moderation, and collimation that maximises the sensitivity of neutron-sensitive RPMs. These structures, which could be simply and cost-effectively added to existing RPMs, can improve the detector response by more than a factor of two relative to an unmodified, bare design. Furthermore, optimisation of the air gap surrounding the helium tubes also improves detector efficiency.

A large number of materials exist which have been labeled as low activation structural materials (LAM). Most often, these materials have been designed in order to substitute-out or completely remove elements that become activated and contribute significantly to shut-down activity after being irradiated by neutrons in a reactor environment. To date, one of the fundamental principles from which LAMs have been developed is that natural elemental compositions are the building blocks of LAMs. Thus, elements such as Co, Al, Ni, Mo, Nb, N and Cu that produce long-lived decay products are significantly reduced or removed from the LAM composition. These elements have an important part to play in the composition of steels and the removal/substitution can have a negative impact on materials properties such as yield stress and fracture toughness. This paper looks in more detail at whether using isotopic selection of the more mechanically desirable, but prohibited due to activation, elements can improve matters. In particular, this paper focuses on the activation of Eurofer. Carefully chosen isotopically enriched elements, which are normally considered to be on the prohibited element list, are added to EUROFER steel as potential alloying elements. The EUROFER activation results show that some prohibited elements can be used as alloying elements in LAM steels, providing the selected isotopes do not have a significant impact on waste disposal rating or shut-down dose. The economic implications of isotopically enriching elements and the potential implications for decommissioning are considered. It is shown that the addition of molybdenum and nickel in small concentrations ( Another important issue for materials exposed to neutron irradiation is the production of gases, in particular helium, as a result of nuclear interactions. Helium accumulation in materials can cause embrittlement and so mitigating the rate of production is an important consideration when selecting materials. The second part of this paper considers whether helium production can be reduced in CuCrZr by isotopic tailoring. CuCrZr is a candidate bonding material for tungsten at first wall locations, however it suffers from degradation due to helium production. Inventory calculations show that isotopically enriching the copper, in CuCrZr, can reduce helium production by approximately 50%. However, cost–benefit analysis suggests that the cost of enriching copper is not cost-effective due to the high price of electromagnetic enrichment that is required for copper.

Defect microstructures formed in ion-irradiated metals, for example iron or tungsten, often exhibit patterns of spatially ordered nano-scale dislocation loops. We show that such ordered dislocation loop structures may form spontaneously as a result of Brownian motion of loops, biased by the angular-dependent elastic interaction between the loops. Patterns of spatially ordered loops form once the local density of loops produced by ion irradiation exceeds a critical threshold value., 6 pages, 5 figures

The methodological approach employed for the neutronics in the PPPT (Power Plant Physics and Technology) programme of EUROfusion is presented. It encompasses development works on advanced computational tools and activities related to the nuclear design and performance evaluation of the DEMO power plant including safety, maintenance, and waste management issues. Development work is conducted on Monte Carlo codes, on the CAD geometry conversion for Monte Carlo simulations, and on coupled radiation transport and activation computation systems. The role of nuclear data for reliable DEMO neutronics design analyses and uncertainty assessments is also addressed. Specific examples of nuclear analyses are presented including breeder blanket and shielding analyses for the different DEMO blanket concepts as well as related activation, decay heat and shut-down dose rate analyses.

The findings of the EU Fusion Programme's 'Materials Assessment Group' (MAG), assessing readiness of Structural, Plasma Facing (PF) and High Heat Flux (HHF) materials for DEMO, are discussed. These are incorporated into the EU Fusion Power Roadmap [1] , with a decision to construct DEMO in the early 2030s. The methodology uses project-based and systems-engineering approaches, the concept of Technology Readiness Levels, and considers lessons learned from Fission reactor material development. 'Baseline' materials are identified for each DEMO role, and the DEMO mission risks analysed from the known limitations, or unknown properties, associated with each baseline material. RD programmes to address these risks are developed. The DEMO assessed has a phase I with a 'starter blanket': the blanket must withstand >= 2 MW yr m(-2) fusion neutron flux (equivalent to similar to 20 dpa front-wall steel damage). The baseline materials all have significant associated risks, so development of 'Risk Mitigation Materials' (RMM) is recommended. The RD programme has parallel development of the baseline and RMM, up to 'down-selection' points to align with decisions on the DEMO blanket and divertor engineering definition. ITER licensing experience is used to refine the issues for materials nuclear testing, and arguments are developed to optimise scope of materials tests with fusion neutron ('14MeV') spectra before DEMO design finalisation. Some 14 MeV testing is still essential, and the Roadmap requires deployment of a >= 30 dpa (steels) testing capability by 2026. Programme optimisation by the pre-testing with fission neutrons on isotopically- or chemically-doped steels and with ion-beams is discussed along with the minimum 14 MeV testing programme, and the key role which fundamental and mission-oriented modelling can play in orienting the research. (C) 2013 Elsevier B.V. All rights reserved.

As part of CCFE's nuclear data and technology programmes a series of material irradiations have been performed at the ASP accelerator to determine integral reaction cross-sections for fusion relevant materials. The integral reaction cross section can be used as part of the validation of the cross section data. The ASP machine accelerates deuterons onto a tritiated target to produce approximately 14 MeV neutrons via the D–T fusion reaction. These neutrons interact with the material creating radioactive isotopes. The gamma emissions from the activated products are then measured using a high resolution gamma spectroscopy system. An important part of evaluating the results of these and future experiments lies in an accurate determination of the neutron energy spectrum. Initially a neutron spectrum determined by MCNP modelling was used based on a source term calculated using relativistic kinematics. The work reported here improves the understanding of the neutron spectrum using a combination of enhanced modelling and experimental data as input information to be used in spectrum unfolding. Recent advances in simulation techniques allow us to use deuteron cross sections for low energy deuterons and hence model the production of neutrons by the deuterons explicitly. This means that it is possible to model the effect of changing various deuteron beam parameters such as radius, energy and position on the target to understand what influence these have on the spectrum seen at the material of interest. The spectrum unfolding, based on threshold reactions, has not previously been performed for the ASP accelerator and provides an experimental method to improve the understanding of the neutron spectrum in the irradiation position. The combination of both modelling and experimental work to improve the understanding of the neutron spectrum has led to better understanding of the facility and the influences on the neutron spectrum. The combination of modelling and experimental work performed in this work to characterise the ASP neutron spectrum may also be applicable to other current and future neutron irradiation facilities such as IFMIF where an accurate knowledge of the neutron spectrum in each irradiation location will be required.

This work presents new integral data measured at the ASP 14 MeV neutron irradiation facility at Aldermaston in the UK, which has recently become available for fusion-related work through the CCFE materials programme. Measurements of reaction products from activation experiments using elemental foils were carried out using gamma spectrometry in a high efficiency, high-purity germanium (HPGe) detector and associated digital signal processing hardware. Following irradiation and rapid extraction to the measurement cell, gamma emissions were acquired with both energy and time bins. Integral cross section and half-life data have been derived from these measurements. Selected integral cross section values are presented from the measurement campaigns., 4 pages, 5 figures

Efficacy and acute toxicity of proton craniospinal irradiation (p-CSI) were compared with conventional photon CSI (x-CSI) for adults with medulloblastoma.Forty adult medulloblastoma patients treated with x-CSI (n=21) or p-CSI (n=19) at the University of Texas MD Anderson Cancer Center from 2003 to 2011 were retrospectively reviewed. Median CSI and total doses were 30.6 and 54 Gy, respectively. The median follow-up was 57 months (range 4-103) for x-CSI patients and 26 months (range 11-63) for p-CSI.p-CSI patients lost less weight than x-CSI patients (1.2% vs 5.8%; P=.004), and less p-CSI patients had5% weight loss compared with x-CSI (16% vs 64%; P=.004). p-CSI patients experienced less grade 2 nausea and vomiting compared with x-CSI (26% vs 71%; P=.004). Patients treated with x-CSI were more likely to have medical management of esophagitis than p-CSI patients (57% vs 5%, P.001). p-CSI patients had a smaller reduction in peripheral white blood cells, hemoglobin, and platelets compared with x-CSI (white blood cells 46% vs 55%, P=.04; hemoglobin 88% vs 97%, P=.009; platelets 48% vs 65%, P=.05). Mean vertebral doses were significantly associated with reductions in blood counts.This report is the first analysis of clinical outcomes for adult medulloblastoma patients treated with p-CSI. Patients treated with p-CSI experienced less treatment-related morbidity including fewer acute gastrointestinal and hematologic toxicities.

In support of the technological requirements for fusion, the UK fusion technology programme is conducting several experiments using the ASP DT neutron irradiation facility at Aldermaston. The present experimental programme covers two key areas of technology development: improving the quality of nuclear cross-section data required for fusion-related materials; and benchmarking fusion nuclear analysis tools such as the shutdown activation dose system MC-R2S. The first of these areas is the focus of this paper. The work presented here gives a technical overview of the ASP facility, including the accelerator, the irradiation cell, the recently re-commissioned fast sample extraction system and ancillary radiation metrology equipment. Results from preliminary activation experiments using high purity elemental- and fusion-relevant material foils, are presented. These include measurements of short-lived activation products conducted via gamma spectrometry methods.

Purpose To assess the efficacy and toxicity of chemotherapy consisting of cyclophosphamide, doxorubicin (Adriamycin), vincristine, and dexamethasone (CHOD) plus bis-chloronitrosourea (BCNU), cytosine arabinoside, and methotrexate (BVAM) followed by whole-brain irradiation (WBRT) for patients with primary central nervous system lymphoma (PCNSL). Methods and Materials Patients 70 years old and younger with newly diagnosed, biopsy-proven PCNSL received one cycle of CHOD followed by two cycles of BVAM. Patients then received WBRT, 30.6 Gy, if a complete response was evoked, or 50.4 Gy if the response was less than complete; both doses were given in 1.8-Gy daily fractions. The primary efficacy endpoint was 1-year survival. Results Thirty-six patients (19 men, 17 women) enrolled between 1995 and 2000. Median age was 60.5 years (range, 34 to 69 years). Thirty (83%) patients had baseline Eastern Cooperative Oncology Group performance scores of 0 to 1. All 36 patients were eligible for survival and response evaluations. Median time to progression was 12.3 months, and median survival was 18.5 months. The percentages of patients alive at 1, 2, and 3 years were 64%, 36%, and 33%, respectively. The best response was complete response in 10 patients and immediate progression in 7 patients. Ten (28%) patients had at least one grade 3 or higher neurologic toxicity. Conclusions This regimen did improve the survival of PCNSL patients but also caused substantial toxicity. The improvement in survival is less than that reported with high-dose methotrexate-based therapies.

Purpose: To conduct a controlled trial of bevacizumab for the treatment of symptomatic radiation necrosis of the brain. Methods and Materials: A total of 14 patients were entered into a placebo-controlled randomized double-blind study of bevacizumab for the treatment of central nervous system radiation necrosis. All patients were required to have radiographic or biopsy proof of central nervous system radiation necrosis and progressive neurologic symptoms or signs. Eligible patients had undergone irradiation for head-and-neck carcinoma, meningioma, or low- to mid-grade glioma. Patients were randomized to receive intravenous saline or bevacizumab at 3-week intervals. The magnetic resonance imaging findings 3 weeks after the second treatment and clinical signs and symptoms defined the response or progression. Results: The volumes of necrosis estimated on T2-weighted fluid-attenuated inversion recovery and T1-weighted gadolinium-enhanced magnetic resonance imaging scans demonstrated that although no patient receiving placebo responded (0 of 7), all bevacizumab-treated patients did so (5 of 5 randomized and 7 of 7 crossover) with decreases in T2-weighted fluid-attenuated inversion recovery and T1-weighted gadolinium-enhanced volumes and a decrease in endothelial transfer constant. All bevacizumab-treated patients - and none of the placebo-treated patients - showed improvement in neurologic symptoms or signs. At a median of 10 months after the last dose of bevacizumab in patients receiving all four study doses, only 2 patients had experienced a recurrence of magnetic resonance imaging changes consistent with progressive radiation necrosis; one patient received a single additional dose of bevacizumab and the other patient received two doses. Conclusion: The Class I evidence of bevacizumab efficacy from the present study in the treatment of central nervous system radiation necrosis justifies consideration of this treatment option for people with radiation necrosis secondary to the treatment of head-and-neck cancer and brain cancer. © 2011 Elsevier Inc.

Adequate prediction of the activation and transmutation response of materials under fusion neutron irradiation is heavily reliant on the quality of the nuclear data used in inventory calculations. Foil irradiation experiments have been conducted using a 14 MeV DT neutron source hosted at AWE Aldermaston in the UK as part of an effort to improve and increase the integral data available for input to the nuclear cross section database. An automated processing system has been developed to handle the huge number of γ -spectra generated from these experiments. As well as providing a framework in which to process a large number of separate experiments automatically and in a consistent manner, the system also allows for the time-dependent γ -spectra available for an individual experiment to be considered as a whole, thereby improving the accuracy of measurements in comparison to those based on a single time-integrated spectrum.

This paper presents preliminary integral cross section data recently measured at the ASP 14 MeV neutron irradiation facility. Reaction cross sections were derived from neutron activated elemental foils following measurement of resulting activation product gamma emissions as a function of time and energy using a HPGe detector, with associated signal processing and data post processing tools. Selected measurements are compared with facility spectrum-averaged cross sections, calculated using the latest release of the FISPACT-II inventory code and TENDL-2011 groupwise cross section data. Examples are shown as plots of the C/E ratio. Measurements are compared with integral data derived from other neutron irradiation facilities. Together, with differential cross section measurements taken from the EXFOR database maintained by the IAEA, we briefly highlight how C/E plots contribute to validation and improvement of activation libraries.

The evolution of radiation damage under heavy-ion irradiation in thin foils of pure bcc Fe has been investigated by simulation and experiment. Simulations showed that vacancy loops are about as mobile as interstitial loops, and can be lost to the surface of a foil. Consistent with this, in situ real-time dynamic observations of the damage evolution showed that loops, many of which are believed to be of vacancy nature, were mobile and were often lost during irradiation. Atomistic simulations of vacancy defects in Fe showed that spherical voids, rather than vacancy loops, represent the lowest energy configurations for clusters of vacancies of any size. The simulations also indicated that the stability of loops strongly varies depending on their size. Closed loops above a critical diameter (∼2 nm) are highly metastable due to the difficulty of their transformation into voids. The greater stability of voids explains why the loop yield in Fe and other ferritic materials is very low.

The accurate diagnosis and management of patients who have infiltrating low-grade gliomas is increasing in importance. Recent advances in molecular characterization, imaging, and treatment of these tumors underscore this current focus of investigations.

This study explored the use of complementary and alternative medicine (CAM) approaches and their relationship with demographic and disease characteristics and quality of life (QOL) in the primary brain tumor (PBT) population. One hundred one PBT patients were enrolled in this study. The results showed that 34% of patients reported using CAM. Forty-one percent reported using more than one type of CAM. The average cost of each CAM used per month was 69 dollars, with 20% of patients spending more than 100 dollars per month. The majority (74%) reported that their physicians were unaware of their use of CAM. Data analysis found a higher performance status to be the only factor significantly related to use of CAM therapy (P < 0.005). There was no difference in patient report of QOL between users and nonusers of CAM therapies. The high number of patients who do not report CAM use has potential implications for evaluation of symptoms and response to therapy in this population. This may be especially relevant in those patients with higher functional status participating in clinical trials.

Investigation of current and planned fusion devices, as well as conceptual power plants, requires well-validated tools to predict the activation of materials. This has led to the production of the European Activation System (EASY), which provides such a capability. The version used here, EASY-2003, is widely distributed and has been used to carry out activation calculations on a large number of materials. However, there was also a need for a comprehensive handbook of activation data that could be quickly referred to, rather than resorting to running codes. This paper discusses the process of generating, over a period of 8 months, the data for a handbook that presents the important activation data for all the naturally occurring elements from hydrogen to uranium. The main computational methods are outlined briefly, but the bulk of the paper is focused toward a description of the different ways in which the data are presented, including new presentations of activation data, called ‘importance diagrams’.

The designation of a tumor as anaplastic astrocytoma (AA) reflects a distinct histologic classification of malignant glioma characterized by an abundance of pleomorphic astrocytes with evidence of mitosis. Although these tumors are malignant, they have a better prognosis and a higher likelihood of response to treatment than glioblastoma. Despite advances in brain tumor imaging, making an accurate diagnosis requires the evaluation of tumor tissue and is essential for treatment planning. Currently, most patients undergo maximal surgical debulking of tumor followed by external beam radiation, often with subsequent adjuvant chemotherapy. However, despite the use of these treatment modalities, most tumors recur within a few years and these recurrent tumors are more refractory to subsequent therapies. This review examines the diagnosis, prognosis, and treatment of AAs. Ongoing clinical research investigations are also summarized, reflecting advances in our knowledge of the molecular pathogenesis of these tumors and providing hope for significant improvements in patient outcomes.