The ICRU Proposal for New Operational Quantities for External Radiation.

Report Committee 26 of the ICRU proposes a set of operational quantities for radiation protection for external radiation, directly based on effective dose and for an extended range of particles and energies. It is accompanied by quantities for estimating deterministic effects to the eye lens and the local skin. The operational quantities are designed to overcome the conceptual and technical shortcomings of those presently in use. This paper describes the proposed operational quantities, and highlights the improvements with respect to the present, legal monitoring quantities.

ICRP, 123. Assessment of radiation exposure of astronauts in space. ICRP Publication 123.

During their occupational activities in space, astronauts are exposed to ionising radiation from natural radiation sources present in this environment. They are, however, not usually classified as being occupationally exposed in the sense of the general ICRP system for radiation protection of workers applied on Earth. The exposure assessment and risk-related approach described in this report is clearly restricted to the special situation in space, and should not be applied to any other exposure situation on Earth. The report describes the terms and methods used to assess the radiation exposure of astronauts, and provides data for the assessment of organ doses. Chapter 1 describes the specific situation of astronauts in space, and the differences in the radiation fields compared with those on Earth. In Chapter 2, the radiation fields in space are described in detail, including galactic cosmic radiation, radiation from the Sun and its special solar particle events, and the radiation belts surrounding the Earth. Chapter 3 deals with the quantities used in radiological protection, describing the Publication 103 (ICRP, 2007) system of dose quantities, and subsequently presenting the special approach for applications in space; due to the strong contribution of heavy ions in the radiation field, radiation weighting is based on the radiation quality factor, Q, instead of the radiation weighting factor, wR. In Chapter 4, the methods of fluence and dose measurement in space are described, including instrumentation for fluence measurements, radiation spectrometry, and area and individual monitoring. The use of biomarkers for the assessment of mission doses is also described. The methods of determining quantities describing the radiation fields within a spacecraft are given in Chapter 5. Radiation transport calculations are the most important tool. Some physical data used in radiation transport codes are presented, and the various codes used for calculations in high-energy radiation fields in space are described. Results of calculations and measurements of radiation fields in spacecraft are given. Some data for shielding possibilities are also presented. Chapter 6 addresses methods of determining mean absorbed doses and dose equivalents in organs and tissues of the human body. Calculated conversion coefficients of fluence to mean absorbed dose in an organ or tissue are given for heavy ions up to Z=28 for energies from 10 MeV/u to 100 GeV/u. For the same set of ions and ion energies, mean quality factors in organs and tissues are presented using, on the one hand, the Q(L) function defined in Publication 60 (ICRP, 1991), and, on the other hand, a Q function proposed by the National Aeronautics and Space Administration. Doses in the body obtained by measurements are compared with results from calculations, and biodosimetric measurements for the assessment of mission doses are also presented. In Chapter 7, operational measures are considered for assessment of the exposure of astronauts during space missions. This includes preflight mission design, area and individual monitoring during flights in space, and dose recording. The importance of the magnitude of uncertainties in dose assessment is considered. Annex A shows conversion coefficients and mean quality factors for protons, charged pions, neutrons, alpha particles, and heavy ions(2 < Z ≤2 8), and particle energies up to 100 GeV/u.

Improved diagnosis of central venous catheter-related bloodstream infections using the HB&L UROQUATTRO™ system.

The diagnosis of catheter-related bloodstream infections (CRBSIs) in febrile patients with indwelling central venous catheters (CVCs) needs improvement. To diagnose CRBSIs more efficiently, we have developed a novel culture approach using the catheter tips removed from febrile patients. CVCs and blood cultures from 1,070 patients with only CVC-related infections were obtained over a period of 3 years (January 2009 to December 2011). The CVCs were evaluated by a semi-quantitative catheter culture method according to Maki's method and by our novel method, which is based on the use of the HB&L UROQUATTRO™ system (Alifax, Padova, Italy). Using our new method, 571 (571/1,070) of the infections were confirmed as CRBSIs. The remaining 487 patients had infections that were associated with hematologic malignancies, neutropenia, prior exposure to antibiotics, and a decreased CVC removal rate. Twelve samples were identified as false-positives. The percentage of patients with CRBSIs confirmed using the HB&L UROQUATTRO™ system was 53.36 % versus 34.95 % (p-value 0.004) using Maki's method (374/1,070 CVC Maki-positive samples). Our results indicate that our new culture method allows for an improved CRBSI diagnosis rate. A significant number of tip cultures (18.41 %) tested positive for CRBSIs using our system but were negative when tested using Maki's method. Moreover, the use of the HB&L UROQUATTRO™ system allowed us to significantly reduce diagnosis time; a negative CRBSI diagnosis could be made within 6 h and a positive diagnosis could be made within 22-28 h.

The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND): test development and reliability.

The motor skills of patients with spinal muscular atrophy, type I (SMA-I) are very limited. It is difficult to quantify the motor abilities of these patients and as a result there is currently no validated measure of motor function that can be utilized as an outcome measure in clinical trials of SMA-I. We have developed the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders ("CHOP INTEND") to evaluate the motor skills of patients with SMA-I. The test was developed following the evaluation of 26 infants with SMA-I mean age 11.5 months (1.4-37.9 months) with the Test of Infant Motor Performance and The Children's Hospital of Philadelphia Test of Strength in SMA, a newly devised motor assessment for SMA. Items for the CHOP INTEND were selected by an expert panel based on item mean and standard deviation, item frequency distribution, and Chronbach's alpha. Intra-rater reliability of the resulting test was established by test-retest of 9 infants with SMA-I over a 2 month period; Intraclass correlation coefficient (ICC) (3,1)=0.96. Interrater reliability was by video analysis of a mixed group of infants with neuromuscular disease by 4 evaluators; ICC (3,4)=0.98 and in a group of 8 typically developing infants by 5 evaluators ICC (3,5)=0.93. The face validity of the CHOP INTEND is supported by the use of an expert panel in item selection; however, further validation is needed. The CHOP INTEND is a reliable measure of motor skills in patients with SMA-I and neuromuscular disorders presenting in infancy.

Measurements and simulations of the radiation exposure to aircraft crew workplaces due to cosmic radiation in the atmosphere.

As required by the European Directive 96/29/Euratom, radiation exposure due to natural ionizing radiation has to be taken into account at workplaces if the effective dose could become more than 1 mSv per year. An example of workers concerned by this directive is aircraft crew due to cosmic radiation exposure in the atmosphere. Extensive measurement campaigns on board aircrafts have been carried out to assess ambient dose equivalent. A consortium of European dosimetry institutes within EURADOS WG5 summarized experimental data and results of calculations, together with detailed descriptions of the methods for measurements and calculations. The radiation protection quantity of interest is the effective dose, E (ISO). The comparison of results by measurements and calculations is done in terms of the operational quantity ambient dose equivalent, H(10). This paper gives an overview of the EURADOS Aircraft Crew In-Flight Database and it presents a new empirical model describing fitting functions for this data. Furthermore, it describes numerical simulations performed with the Monte Carlo code FLUKA-2005 using an updated version of the cosmic radiation primary spectra. The ratio between ambient dose equivalent and effective dose at commercial flight altitudes, calculated with FLUKA-2005, is discussed. Finally, it presents the aviation dosimetry model AVIDOS based on FLUKA-2005 simulations for routine dose assessment. The code has been developed by Austrian Research Centers (ARC) for the public usage (http://avidos.healthphysics.at).

The Hammersmith functional score correlates with the SMN2 copy number: a multicentric study.

Previous studies showed that SMN2 copy number correlates inversely with the disease severity. Our aim was to evaluate SMN2 copy numbers and the Hammersmith functional motor scale in 87 patients with SMA II in order to establish whether, within SMAII, the number of copies correlates with the severity of functional impairment. Our results showed a relative variability of functional scores, but a significant correlation between the number of SMN2 genes and the level of function.

Randomized, double-blind, placebo-controlled trial of phenylbutyrate in spinal muscular atrophy.

OBJECTIVE: To assess the efficacy of phenylbutyrate (PB) in patients with spinal muscular atrophy in a randomized, double-blind, placebo-controlled trial involving 10 Italian centers. METHODS: One hundred seven children were assigned to receive PB (500 mg/kg/day) or matching placebo on an intermittent regimen (7 days on/7 days off) for 13 weeks. The Hammersmith functional motor scale (primary outcome measure), myometry, and forced vital capacity were assessed at baseline and at weeks 5 and 13. RESULTS: Between January and September 2004, 107 patients aged 30 to 154 months were enrolled. PB was well tolerated, with only one child withdrawing because of adverse events. Mean improvement in functional score was 0.60 in the PB arm and 0.73 in placebo arm (p = 0.70). Changes in the secondary endpoints were also similar in the two study arms. CONCLUSIONS: Phenylbutyrate was not effective at the regimen, schedule, and duration used in this study.

Human exposure to space radiation: role of primary and secondary particles.

Human exposure to space radiation implies two kinds of risk, both stochastic and deterministic. Shielding optimisation therefore represents a crucial goal for long-term missions, especially in deep space. In this context, the use of radiation transport codes coupled with anthropomorphic phantoms allows to simulate typical radiation exposures for astronauts behind different shielding, and to calculate doses to different organs. In this work, the FLUKA Monte Carlo code and two phantoms, a mathematical model and a voxel model, were used, taking the Galactic Cosmic Rays (GCR) spectra from the model of Badhwar and O'Neill. The time integral spectral proton fluence of the August 1972 Solar Particle Event (SPE) was represented by an exponential function. For each aluminium shield thickness, besides total doses the contributions from primary and secondary particles for different organs and tissues were calculated separately. More specifically, organ-averaged absorbed doses, dose equivalents and a form of 'biological dose', defined on the basis of initial (clustered) DNA damage, were calculated. As expected, the SPE doses dramatically decreased with increasing shielding, and doses in internal organs were lower than in skin. The contribution of secondary particles to SPE doses was almost negligible; however it is of note that, at high shielding (10 g cm(-2)), most of the secondaries are neutrons. GCR organ doses remained roughly constant with increasing Al shielding. In contrast to SPE results, for the case of cosmic rays, secondary particles accounted for a significant fraction of the total dose.

Reliability of the Hammersmith functional motor scale for spinal muscular atrophy in a multicentric study.

The aim of this study was to validate the Hammersmith functional motor scale for children with spinal muscular atrophy in a large cohort of 90 non-ambulant children with spinal muscular atrophy type 2 or 3. All had a baseline assessment (T0) and were reassessed either at 3 months (T1) (n = 66) or at 6 months (T2) (n = 24). Inter-observer reliability, tested on 13 children among 3 examiners, was > 95%. Of the 66 children examined after 3 months 4 had adverse effects in between assessments and were excluded from the analysis. Forty-two (68%) of the remaining 62 reassessed had no variation in scores between T0 and T1 and 13 (21%) were within +/- 1 point. 9 (37.5%) of the 24 children reassessed after 6 months had no variation in scores between T0 and T2 and another 9 (37.5%) had variations within +/- 1 point. Our study confirms previous observations of the reliability of the scale and helps to establish a baseline for assessing changes of functional ability over 3 and 6 month intervals. This information can be valuable in view of therapeutic trials.

The FLUKA code: new developments and application to 1 GeV/n iron beams.

The modeling of ion transport and interactions in matter is a subject of growing interest, driven by the continuous increase of possible application fields. These include hadron therapy, dosimetry, and space missions, but there are also several issues involving fundamental research, accelerator physics, and cosmic ray physics, where a reliable description of heavy ion induced cascades is important. In the present work, the capabilities of the FLUKA code for ion beams will be briefly recalled and some recent developments presented. Applications of the code to the simulation of therapeutic carbon, nitrogen and oxygen ion beams, and of iron beams, which are of direct interest for space mission related experiments, will be also presented together with interesting consideration relative to the evaluation of dosimetric quantities. Both applications involve ion beams in the AGeV range.

FLUKA simulation of TEPC response to cosmic radiation.

The aircrew exposure to cosmic radiation can be assessed by calculation with codes validated by measurements. However, the relationship between doses in the free atmosphere, as calculated by the codes and from results of measurements performed within the aircraft, is still unclear. The response of a tissue-equivalent proportional counter (TEPC) has already been simulated successfully by the Monte Carlo transport code FLUKA. Absorbed dose rate and ambient dose equivalent rate distributions as functions of lineal energy have been simulated for several reference sources and mixed radiation fields. The agreement between simulation and measurements has been well demonstrated. In order to evaluate the influence of aircraft structures on aircrew exposure assessment, the response of TEPC in the free atmosphere and on-board is now simulated. The calculated results are discussed and compared with other calculations and measurements.

A mathematical model of aircraft for evaluating the effects of shielding structure on aircrew exposure.

To investigate the influence of the aircraft structures and contents on the exposure of aircrew to the galactic component of cosmic rays, a mathematical model of an aeroplane has been developed. The irradiation of the mathematical model in the cosmic ray environment has been simulated using the Monte Carlo transport code FLUKA. Effective dose andambient dose-equivalent rates have been determined inside the aircraft at several locations along the fuselage at a typicaI civil aviation altitude. A significant effect of the shielding of aircraft structures has been observed on the ambient dose-equivalent rates, while the impact on the effective dose rates seems to be minor. Care should be taken in positioning the detectors onboard when the measurements are aimed at validating the codes.

Monte Carlo calculation of the angular distribution of cosmic rays at flight altitudes.

The angular distribution of the secondary radiation produced by the galactic component of cosmic rays has been determined by simulating the penetration of the primary spectra in the Earth's atmosphere. The simulations have been carried out with the latest version of the FLUKA code. Particles have been scored at various altitudes according to their angle of incidence for some significant values of vertical cut-off rigidity and solar modulation parameter. The calculated results at typical cruise altitudes for a civil aircraft are presented. The data at 10.7 km have been fitted with simple mathematical equations. It has been demonstrated that the major contribution to the doses at aviation altitudes arises from downward-directed particles. The isotropic irradiation usually assumed for the evaluation of aircrew exposure could be a very poor approximation.

Dosimetric considerations on TEPC fluka-simulation and measurements.

The response of a tissue equivalent proportional counter (TEPC) has been simulated with the Monte Carlo transport code FLUKA. The absorbed dose distribution of lineal energy y has been determined for several monoenergetic photon and neutron sources. The agreement between the calculated results and the measurements carried out with different well-known sources is well demonstrated. Work is in progress in order to evaluate the response of the instrument in the cosmic ray environment.

The impact of ICRP publication 92 on the conversion coefficients in use for cosmic ray dosimetry.

ICRP Publication 92 presents a proposal to achieve coherence between radiation weighting factors and quality factors. In particular, the radiation weighting factors for incident protons and neutrons have been revised and new values have been proposed. On the basis of the proposed values, sets of conversion coefficients fluence-to-effective dose for protons and neutrons have been derived for the irradiation geometries of interest for cosmic ray dosimetry.

Evaluation of the influence of aircraft shielding on the aircrew exposure through an aircraft mathematical model.

In order to investigate the influence of aircraft shielding on the galactic component of cosmic rays, an aircraft mathematical model has been developed by the combinatorial geometry package of the Monte-Carlo transport code FLUKA. The isotropic irradiation of the aircraft in the cosmic ray environment has been simulated. Effective dose and ambient dose equivalent rates have been determined inside the aircraft at several locations along the fuselage, at a typical civil aviation altitude (10 580 m), for vertical cut-off rigidity of 0.4 GV (poles) and 17.6 GV (equator) and deceleration potential of 465 MV. The values of both quantities were generally lower than those in the free atmosphere. They depend, in an intricate manner, on the location within the aircraft, quantity of fuel, number of passengers, etc. The position onboard of crew members should be taken into account when assessing individual doses. Likewise due consideration must be taken when positioning detectors which are used to measure H*(10). Care would be needed to avoid ambiguity when comparing the results of calculation with the experimental data.

The FLUKA code for space applications: recent developments.

The FLUKA Monte Carlo transport code is widely used for fundamental research, radioprotection and dosimetry, hybrid nuclear energy system and cosmic ray calculations. The validity of its physical models has been benchmarked against a variety of experimental data over a wide range of energies, ranging from accelerator data to cosmic ray showers in the earth atmosphere. The code is presently undergoing several developments in order to better fit the needs of space applications. The generation of particle spectra according to up-to-date cosmic ray data as well as the effect of the solar and geomagnetic modulation have been implemented and already successfully applied to a variety of problems. The implementation of suitable models for heavy ion nuclear interactions has reached an operational stage. At medium/high energy FLUKA is using the DPMJET model. The major task of incorporating heavy ion interactions from a few GeV/n down to the threshold for inelastic collisions is also progressing and promising results have been obtained using a modified version of the RQMD-2.4 code. This interim solution is now fully operational, while waiting for the development of new models based on the FLUKA hadron-nucleus interaction code, a newly developed QMD code, and the implementation of the Boltzmann master equation theory for low energy ion interactions.

Role of shielding in modulating the effects of solar particle events: Monte Carlo calculation of absorbed dose and DNA complex lesions in different organs.

Distributions of absorbed dose and DNA clustered damage yields in various organs and tissues following the October 1989 solar particle event (SPE) were calculated by coupling the FLUKA Monte Carlo transport code with two anthropomorphic phantoms (a mathematical model and a voxel model), with the main aim of quantifying the role of the shielding features in modulating organ doses. The phantoms, which were assumed to be in deep space, were inserted into a shielding box of variable thickness and material and were irradiated with the proton spectra of the October 1989 event. Average numbers of DNA lesions per cell in different organs were calculated by adopting a technique already tested in previous works, consisting of integrating into "condensed-history" Monte Carlo transport codes--such as FLUKA--yields of radiobiological damage, either calculated with "event-by-event" track structure simulations, or taken from experimental works available in the literature. More specifically, the yields of "Complex Lesions" (or "CL", defined and calculated as a clustered DNA damage in a previous work) per unit dose and DNA mass (CL Gy-1 Da-1) due to the various beam components, including those derived from nuclear interactions with the shielding and the human body, were integrated in FLUKA. This provided spatial distributions of CL/cell yields in different organs, as well as distributions of absorbed doses. The contributions of primary protons and secondary hadrons were calculated separately, and the simulations were repeated for values of Al shielding thickness ranging between 1 and 20 g/cm2. Slight differences were found between the two phantom types. Skin and eye lenses were found to receive larger doses with respect to internal organs; however, shielding was more effective for skin and lenses. Secondary particles arising from nuclear interactions were found to have a minor role, although their relative contribution was found to be larger for the Complex Lesions than for the absorbed dose, due to their higher LET and thus higher biological effectiveness.

On the conversion coefficients for cosmic ray dosimetry.

Calculations of fluence-to-effective dose conversion coefficients have typically been limited to the standard irradiation geometries of the human body: anterior-to-posterior (AP), posterior-to-anterior (PA), lateral from the right side to the left side (RLAT), lateral from the left side to the right side (LLAT), rotational around the vertical axis (ROT), and isotropic incidence from all directions (ISO). In order to estimate the doses to air crew members exposed to cosmic radiation, the geometrical conditions of irradiation are usually assumed to be isotropic. However, the assumption of isotropic irradiation is in many cases invalid for the high energy component of the radiation field, which is often peaked in the forward direction. Therefore, it was considered useful to extend the calculations of conversion coefficients to other geometries. New sets of conversion coefficients fluence-to-effective dose are presented for the semi-isotropic irradiation of the human body and for the irradiation from the top. Their application to cosmic ray dosimetry is discussed.