Technical developments at the NASA Space Radiation Laboratory

The NASA Space Radiation Laboratory (NSRL) located at Brookhaven National Laboratory (BNL) is a center for space radiation research in both the life and physical sciences. BNL is a multidisciplinary research facility operated for the Office of Science of the US Department of Energy (DOE). The BNL scientific research portfolio supports a large and diverse science and technology program including research in nuclear and high-energy physics, material science, chemistry, biology, medial science, and nuclear safeguards and security. NSRL, in operation since July 2003, is an accelerator-based facility which provides particle beams for radiobiology and physics studies (Lowenstein in Phys Med 17(supplement 1):26–29 2001). The program focus is to measure the risks and to ameliorate the effects of radiation encountered in space, both in low earth orbit and extended missions beyond the earth. The particle beams are produced by the Booster synchrotron, an accelerator that makes up part of the injector sequence of the DOE nuclear physics program’s Relativistic Heavy Ion Collider. Ion species from protons to gold are presently available, at energies ranging from <100 to >1,000 MeV/n. The NSRL facility has recently brought into operation the ability to rapidly switch species and beam energy to supply a varied spectrum onto a given specimen. A summary of past operation performance, plans for future operations and recent and planned hardware upgrades will be described. Work performed under the auspices of the auspices of the US National Aeronautics and Space Administration and the US Department of Energy.     

COTS Silicon diodes as radiation detectors in proton and heavy charged particle radiotherapy 1

Modern radiotherapy facilities for cancer treatment such as the Heavy Ion Therapy Center (HIT) in Heidelberg, Germany, allow for sub-millimeter precision in dose deposition. For measurement of such dose distributions and characterization of the particle beams, detectors with high spatial resolution are necessary. Here, a detector based on the commercially available COTS photodiode (BPW-34) is presented. When applied in hadronic beams of protons and carbon ions, the detector reproduces dose distribution well, but its response decreases rapidly by radiation damage. However, for MeV photon beams, the detector exhibits a similar behavior as found in diode detectors usually applied in radiotherapy.     

Biobanken

Biobanks have become an indispensable component of biomedical research. However, the long-term and unrestricted use of data and biomaterials included in most biobanks pose several legal, ethical and organizational challenges. Therefore, the German Telematics Platform for Medical Research Networks (TMF) has instigated a number of projects addressing the problems arising from the establishment and maintenance of biobanks, each time aiming at the provision of generic solutions to the research community in the form of texts and concepts. After a representative review of existing biobanks in Germany and Europe we provide an overview of the TMF work on biobanking. In addition, two infrastructural projects will be reviewed which should render biobanking in Germany and Europe more efficient and transparent in the future, namely the “Biobanking and Biomolecular Resources Research Infrastructure”(BBMRI) of the European Commission and the National Biobank Register that is currently being set up by the TMF.     

Ion beam radiobiology and cancer: Time to update ourselves

High-energy protons and carbon ions exhibit an inverse dose profile allowing for increased energy deposition with penetration depth. Additionally, heavier ions like carbon beams have the advantage of a markedly increased biological effectiveness characterized by enhanced ionization density in the individual tracks of the heavy particles, where DNA damage becomes clustered and therefore more difficult to repair, but is restricted to the end of their range. These superior biophysical and biological profiles of particle beams over conventional radiotherapy permit more precise dose localization and make them highly attractive for treating anatomically complex and radioresistant malignant tumors but without increasing the severe side effects in the normal tissue. More than half a century since Wilson proposed their use in cancer therapy, the effects of particle beams have been extensively investigated and the biological complexity of particle beam irradiation begins to unfold itself. The goal of this review is to provide an as comprehensive and up-to-date summary as possible of the different radiobiological aspects of particle beams for effective application in cancer treatment.     

Design of a new tracking device for on-line beam range monitor in carbon therapy

Charged particle therapy is a technique for cancer treatment that exploits hadron beams, mostly protons and carbon ions. A critical issue is the monitoring of the beam range so to check the correct dose deposition to the tumor and surrounding tissues. The design of a new tracking device for beam range real-time monitoring in pencil beam carbon ion therapy is presented. The proposed device tracks secondary charged particles produced by beam interactions in the patient tissue and exploits the correlation of the charged particle emission profile with the spatial dose deposition and the Bragg peak position. The detector, currently under construction, uses the information provided by 12 layers of scintillating fibers followed by a plastic scintillator and a pixelated Lutetium Fine Silicate (LFS) crystal calorimeter. An algorithm to account and correct for emission profile distortion due to charged secondaries absorption inside the patient tissue is also proposed. Finally detector reconstruction efficiency for charged particle emission profile is evaluated using a Monte Carlo simulation considering a quasi-realistic case of a non-homogenous phantom.     

What can particle therapy add to the treatment of prostate cancer?

The treatment of prostate cancer with either protons or carbon ions is not a novelty, and several thousands of patients were treated with hadrontherapy in the past decades. The standard treatment approach consisted in two lateral opposed fields for both protons and carbon ions, mostly delivered with scattered beams and using conventional fractionation and hypofractionation for protons and carbon ions, respectively. Similar (RBE-weighted and BED) doses to photon therapy (XRT) have been delivered, with comparable results in terms of both local control and toxicity. The advancements in dose deposition and image guidance of the early ‘00s that improved the quality of XRT treatments and then allowed for hypofractionation, are being matched with some delay by hadrontherapy in these very years. Pencil beam scanning is now the norm in proton therapy, and volumetric image guidance is being developed in all new hadrontherapy facilities. There is therefore the possibility of truly taking advantage of superior dose distributions of hadrons and safely apply it to innovative treatment protocols, such as an intraprostatic boost and the treatment of larger volume for advanced stage disease. This full integration between the best of technology and new clinical approaches is probably necessary in order to obtain clinical results that are truly superior to the current state of the art of XRT.     

Heavy charged particle radiobiology: using enhanced biological effectiveness and improved beam focusing to advance cancer therapy

Ionizing radiation causes many types of DNA damage, including base damage and single- and double-strand breaks. Photons, including X-rays and γ-rays, are the most widely used type of ionizing radiation in radiobiology experiments, and in radiation cancer therapy. Charged particles, including protons and carbon ions, are seeing increased use as an alternative therapeutic modality. Although the facilities needed to produce high energy charged particle beams are more costly than photon facilities, particle therapy has shown improved cancer survival rates, reflecting more highly focused dose distributions and more severe DNA damage to tumor cells. Despite early successes of charged particle radiotherapy, there is room for further improvement, and much remains to be learned about normal and cancer cell responses to charged particle radiation.     

“Broadbeam” irradiation of mammalian cells using a vertical microbeam facility

A “broadbeam” facility is demonstrated for the vertical microbeam at Surrey’s Ion Beam Centre, validating the new technique used by Barazzuol et al. (Radiat Res 177:651–662, 2012). Here, droplets with a diameter of about 4 mm of 15,000 mammalian cells in suspension were pipetted onto defined locations on a 42-mm-diameter cell dish with each droplet individually irradiated in “broadbeam” mode with 2 MeV protons and 4 MeV alpha particles and assayed for clonogenicity. This method enables multiple experimental data points to be rapidly collected from the same cell dish. Initially, the Surrey vertical beamline was designed for the targeted irradiation of single cells with single counted ions. Here, the benefits of both targeted single-cell and broadbeam irradiations being available at the same facility are discussed: in particular, high-throughput cell irradiation experiments can be conducted on the same system as time-intensive focused-beam experiments with the added benefits of fluorescent microscopy, cell recognition and time-lapse capabilities. The limitations of the system based on a 2 MV tandem accelerator are also discussed, including the uncertainties associated with particle Poisson counting statistics, spread of linear energy transfer in the nucleus and a timed dose delivery. These uncertainties are calculated with Monte Carlo methods. An analysis of how this uncertainty affects relative biological effect measurements is made and discussed.     

PADC nuclear track detector for ion spectroscopy in laser-plasma acceleration

The transparent polymer polyallyl-diglycol-carbonate (PADC), also known as CR-39, is widely used as detector for heavy charged particles at low fluence. It allows for detection of single protons and ions via formation of microscopic tracks after etching in NaOH or KOH solutions. PADC combines a high sensitivity and high specificity with inertness towards electromagnetic noise. Present fields of application include laser-ion acceleration, inertial confinement fusion, radiobiological studies with cell cultures, and dosimetry of nuclear fragments in particle therapy. These require precise knowledge of the energy-dependent response of PADC to different ion species. We present calibration data for a new type of detector material, Radosys RS39, to protons (0.2–3 MeV) and carbon ions (0.6–12 MeV). RS39 is less sensitive to protons than other types of PADC. Its response to carbon ions, however, is similar to other materials. Our data indicate that RS39 allows for measuring carbon ion energies up to 10 MeV only from the track diameters. In addition, it can be used for discrimination between protons and carbon ions in a single etching process.     

A new redox loop formality involving metal-catalysed hydroxide-ion translocation. A hypothetical Cu loop mechanism for cytochrome oxidase

A new hypothetical type of redox loop is described, which translocates hydroxide instead of protons. Conventional protonmotive redox loops use carriers of protons with electrons (e.g. QH2/Q systems) to couple electron transfer to the translocation of protons. The putative hydroxidemotive redox loop uses carriers of hydroxide ions against electrons (e.g. transition-metal centres) to couple electron transfer to the translocation of hydroxide ions. This simple idea leads to the proposal of a hydroxidemotive Cu loop mechanism that may possibly be applicable to the CuA or CuB centre of cytochrome oxidase, and might thus account for the coupling of electron transfer to net proton translocation in that osmoenzyme.     

Analytical Model for Estimating Terrestrial Cosmic Ray Fluxes Nearly Anytime and Anywhere in the World: Extension of PARMA/EXPACS

By extending our previously established model, here we present a new model called “PHITS-based Analytical Radiation Model in the Atmosphere (PARMA) version 3.0,” which can instantaneously estimate terrestrial cosmic ray fluxes of neutrons, protons, ions with charge up to 28 (Ni), muons, electrons, positrons, and photons nearly anytime and anywhere in the Earth’s atmosphere. The model comprises numerous analytical functions with parameters whose numerical values were fitted to reproduce the results of the extensive air shower (EAS) simulation performed by Particle and Heavy Ion Transport code System (PHITS). The accuracy of the EAS simulation was well verified using various experimental data, while that of PARMA3.0 was confirmed by the high R ² values of the fit. The models to be used for estimating radiation doses due to cosmic ray exposure, cosmic ray induced ionization rates, and count rates of neutron monitors were validated by investigating their capability to reproduce those quantities measured under various conditions. PARMA3.0 is available freely and is easy to use, as implemented in an open-access software program EXcel-based Program for Calculating Atmospheric Cosmic ray Spectrum (EXPACS). Because of these features, the new version of PARMA/EXPACS can be an important tool in various research fields such as geosciences, cosmic ray physics, and radiation research.     

Tracing the politics of changing postwar research practices: the export of ‘American’ radioisotopes to European biologists

This paper examines the US Atomic Energy Commission’s radioisotope distribution program, established in 1946, which employed the uranium piles built for the wartime bomb project to produce specific radioisotopes for use in scientific investigation and medical therapy. As soon as the program was announced, requests from researchers began pouring into the Commission’s office. During the first year of the program alone over 1000 radioisotope shipments were sent out. The numerous requests that came from scientists outside the United States, however, sparked a political debate about whether the Commission should or even could export radioisotopes. This controversy manifested the tension between the aims of the Marshall Plan and growing US national security concerns after World War II. Proponents of international circulation of radioisotopes emphasized the political and scientific value of collaborating with European scientists, especially biomedical researchers. In the end, radioisotopes were shipped from the Commission’s Oak Ridge facility to many laboratories in England and continental Europe, where they were used in biochemical research on animals, plants, and microbes. However, the issue of radioisotope export continued to draw political fire in the United States, even after the establishment of national atomic energy facilities elsewhere.     

Prevalence of chronic complications, metabolic control and nutritional intake in type 1 diabetes: comparison between different European regions. EURODIAB Complications Study group.

This study compares the prevalence of chronic complications, the quality of metabolic control and the nutritional intake in people with type 1 diabetes in different European regions. The EURODIAB Complications Study included a sample of 3250 European patients with type 1 diabetes stratified for gender, age and diabetes duration. All examinations were performed using standardised, validated methods. HBA1c, LDL-cholesterol and fasting triglycerides were higher in the eastern European centres than in the southern or north-western European centres. Acute (severe ketoacidosis, severe hypoglycaemia) and chronic diabetes complications (retinopathy, nephropathy, neuropathy, cardiovascular disease) were all considerably more frequent in the eastern European centres. HbA1c was lower in the German centres than in the total EURODIAB cohort or in the north-western European centres, but severe hypoglycaemia and proliferative retinopathy were more common. Persons from the eastern European and the German centres consumed undesirably high amounts of cholesterol, total and saturated fat. Overall, improvements in the prevention, detection and management of diabetes complications in persons with type 1 diabetes are essential throughout Europe, particularly in eastern European regions. Since elevated LDL-cholesterol levels and hypertension were strikingly common in this relatively young cohort of European people with type 1 diabetes, generally more attention should be directed towards an adequate management of these cardiovascular risk factors.     

The Challenging Road towards a Unified Animal Research Network in Europe

Animal models are key in biomedical research as a proof of concept to study complex processes in a physiological context. Despite the small yet crucial role animals play in fundamental and applied research, the value of animal research is recurrently undermined. Lack of openness and transparency encourages misconceptions, which can have a dramatic negative impact on science and medicine. Research centres should use all available resources to ensure that relevant details about their use of animals in research are readily accessible. More concerted efforts by professional advocacy groups devoted to informing about the benefits of biomedical animal research are also crucial. The European Animal Research Association acts as an umbrella organisation providing support to national advocacy groups and coordinating actions in countries in which no advocacy group exists.     

How science will help us move forward in 2021

In 2021, the genetics and genomics community needs to communicate to policymakers how the field of human genetics and genomics is transforming biomedical research and medicine, including its essential role in combatting COVID-19. This is important for ensuring that policies enable a thriving scientific enterprise and provide resources for research advances.

In 2021, the genetics and genomics community needs to communicate to policymakers how the field of human genetics and genomics is transforming biomedical research and medicine, including its essential role in combatting COVID-19. This is important for ensuring that policies enable a thriving scientific enterprise and provide resources for research advances.     

A generic curriculum development model for the biomedical physics component of the educational and training programmes of the non-physics healthcare professions

The objective of the study was the construction of a generic curriculum development model for the use of biomedical physics (BMP) educators teaching the non-physics healthcare professions (HCP) in Europe. A comprehensive, qualitative cross-sectional Europe-wide survey of the curricula delivered by BMP in Faculties of Medicine and Health Sciences (FMHS) was carried out. Curricular content was collected from faculty web-sites, curricular documents and textbooks. The survey data was supplemented with semi-structured interviews and direct observation during onsite visits. The number of faculties studied was 118 from 67 universities spread all over Europe, whilst the number of onsite visits/interviews was 15 (geographically distributed as follows: Eastern Europe 6, North Western Europe 5, and South Western Europe 4). EU legislation, recommendations by European national medical councils, educational benchmark statements by higher education quality assurance agencies, research journals concerning HCP education and other documents relevant to standards in clinical practice and undergraduate education were also analyzed. Best practices and BMP learning outcomes were elicited from the curricular materials, interviews and documentation and these were subsequently used to construct the curriculum development model. A structured, comprehensive BMP learning outcomes inventory was designed in the format required by the European Qualifications Framework (EQF). The structures of the inventory and curriculum development model make them ideally suited for use by BMP involved in European curriculum development initiatives for the HCP.     

EU-OPENSCREEN—chemical tools for the study of plant biology and resistance mechanisms

EU-OPENSCREEN is an academic research infrastructure initiative in Europe for enabling researchers in all life sciences to take advantage of chemical biology approaches to their projects. In a collaborative effort of national networks in 16 European countries, EU-OPENSCREEN will develop novel chemical compounds with external users to address questions in, among other fields, systems and network biology (directed and selective perturbation of signalling pathways), structural biology (compound-target interactions at atomic resolution), pharmacology (early drug discovery and toxicology) and plant biology (response of wild or crop plants to environmental and agricultural substances). EU-OPENSCREEN supports all stages of a tool development project, including assay adaptation, high-throughput screening and chemical optimisation of the ‘hit’ compounds. All tool compounds and data will be made available to the scientific community. EU-OPENSCREEN integrates high-capacity screening platforms throughout Europe, which share a rationally selected compound collection comprising up to 300,000 (commercial and proprietary compounds collected from European chemists). By testing systematically this chemical collection in hundreds of assays originating from very different biological themes, the screening process generates enormous amounts of information about the biological activities of the substances and thereby steadily enriches our understanding of how and where they act.     

Maize introduction into Europe: the history reviewed in the light of molecular data

The resolution that can be obtained from molecular genetic markers affords new prospects for understanding the dispersion of agricultural species from their primary origin centres. In order to study the introduction and the dispersion of maize in Europe, we have characterised a large and representative set of maize populations of both American and European origins for their variation at 29 restriction fragment length polymorphism loci. Polymorphism was higher for American populations than for European populations (respectively, 12.3 and 9.6 alleles per locus, on average), and only a few alleles were specific to European populations. Investigation of genetic similarity between populations from both continents made it possible to identify various types of American maize introduced into Europe at different times or in different places and which have given rise to distinctive European races. Beyond confirming the importance of Caribbean germplasm, the first maize type to be introduced into Europe, this research revealed that introductions of Northern American flint populations have played a key role in the adaptation of maize to the European climate. According to a detailed historical investigation, the introduction of these populations must have occurred shortly after the discovery of the New World.     

Research at the European Synchrotron Radiation Facility medical beamline.

The application of synchrotron radiation in medical research has become a mature field of research at synchrotron facilities worldwide. In the relatively short time that synchrotrons have been available to the scientific community, their characteristic beams of UV and X-ray radiation have been applied to virtually all areas of medical science which use ionizing radiation. The ability to tune intense monochromatic beams over wide energy ranges differentiates these sources from standard clinical and research tools. At the European Synchrotron Radiation Facility (Grenoble, France), a major research facility is operational on an advanced wiggler radiation beamport, ID17. The beamport is designed to carry out a broad range of research ranging from cell radiation biology to in vivo human studies. Medical imaging programs at ID17 include transvenous coronary angiography, computed tomography, mammography and bronchography. In addition, a major research program on microbeam radiation therapy is progressing. This paper will present a very brief overview of the beamline and the imaging and therapy programs.