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The pre-conceptual layout for an electron cyclotron system (ECS) in DEMO is described. The present DEMO ECS considers only equatorial ports for both plasma heating and neoclassical tearing mode (NTM) control. This differs from ITER, where four launchers in upper oblique ports are dedicated to NTM control and one equatorial EC port for heating and current drive (H&CD) purposes as basic configuration. Rather than upper oblique ports, DEMO has upper vertical ports to allow the vertical removal of the large breeding blanket segments. While ITER is using front steering antennas for NTM control, in DEMO the antennas are recessed behind the breeding blanket and called mid-steering antennas, referred to the radially recessed position to the breeding blanket. In the DEMO pre-conceptual design phase two variants are studied to integrate the ECS in equatorial ports. The first option integrates waveguide bundles at four vertical levels inside EC port plugs with antennas with fixed and movable mid-steering mirrors that are powered by gyrotrons, operating at minimum two different multiples of the fundamental resonance frequency of the microwave output window. Alternatively, the second option integrates fixed antenna launchers connected to frequency step-tunable gyrotrons. The first variant is described in this paper, introducing the design and functional requirements, presenting the equatorial port allocation, the port plug design including its maintenance concept, the basic port cell layout, the transmission line system with diamond windows from the tokamak up to the RF building and the gyrotron sources. The ECS design studies are supported by neutronic and tokamak integration studies, quasi-optical and plasma physics studies, which will be summarized. Physics and technological gaps will be discussed and an outlook to future work will be given. © 2021

Significance A massive atmospheric release of radioactive 106Ru occurred in Eurasia in 2017, which must have been caused by a sizeable, yet undeclared nuclear accident. This work presents the most compelling monitoring dataset of this release, comprising 1,100 atmospheric and 200 deposition data points from the Eurasian region. The data suggest a release from a nuclear reprocessing facility located in the Southern Urals, possibly from the Mayak nuclear complex. A release from a crashed satellite as well as a release on Romanian territory (despite high activity concentrations) can be excluded. The model age of the radioruthenium supports the hypothesis that fuel was reprocessed ≤2 years after discharge, possibly for the production of a high-specific activity 144Ce source for a neutrino experiment in Italy., In October 2017, most European countries reported unique atmospheric detections of aerosol-bound radioruthenium (106Ru). The range of concentrations varied from some tenths of µBq·m−3 to more than 150 mBq·m−3. The widespread detection at such considerable (yet innocuous) levels suggested a considerable release. To compare activity reports of airborne 106Ru with different sampling periods, concentrations were reconstructed based on the most probable plume presence duration at each location. Based on airborne concentration spreading and chemical considerations, it is possible to assume that the release occurred in the Southern Urals region (Russian Federation). The 106Ru age was estimated to be about 2 years. It exhibited highly soluble and less soluble fractions in aqueous media, high radiopurity (lack of concomitant radionuclides), and volatility between 700 and 1,000 °C, thus suggesting a release at an advanced stage in the reprocessing of nuclear fuel. The amount and isotopic characteristics of the radioruthenium release may indicate a context with the production of a large 144Ce source for a neutrino experiment.

Gyrotron R&D within the EUROfusion Work Package Heating and Current Drive (WPHCD) is addressing the challenging requirements posed on gyrotrons by the European concept for a demonstration fusion power plant (EU DEMO). These requirements, as specified within WPHCD, ask for highly reliable and robust long-pulse operation of the gyrotron, delivering 2 MW of microwave power at frequencies above 200 GHz with a high overall efficiency above 60% and the option for fast frequency step-tunability. To meet these targets, which are clearly beyond today's state-of-the-art, the R&D activities within WPHCD are organized in five main branches: these are the experimental verification of the advanced coaxial gyrotron technology at long pulses, the development of a coaxial gyrotron meeting the EU DEMO requirements, the development of multi-stage depressed collectors for enhanced energy recovery, the development of large broadband diamond windows to allow fast frequency tunability of the gyrotron, and the studies on further innovations and improvement of critical gyrotron components, in view of optimization of performance, reliability, and industrialization. The paper presents the progress made on these activities, the recent results, and the near-term planning. The major recent achievements include (i) the experimental validation of the fabrication of the new, water-cooled components for the longer-pulse coaxial gyrotron at Karlsruhe Institute of Technology, by demonstrating 2.2 MW at 170 GHz with 33% efficiency without depressed collector, (ii) the design of key components for a 2 MW, 170/204 GHz dual-frequency coaxial gyrotron, (iii) the design of a two-stage depressed collector with 77% efficiency, (iv) the first-ever production, in an industrial plasma reactor, of large chemical vapor deposition diamond wafers of 180 mm diameter, (v) the procurement of an advanced electron gun with coated emitter edges, and (vi) advances in the theoretical and numerical modelling for investigating improved concepts for the gyrotron beam tunnel and cavity. © EURATOM 2019.

Long-term options for a steady-state DEMOnstration power plant may require the availability of gyrotrons with an operating frequency significantly above 200 GHz together with an RF output power of more than 1 MW and a total gyrotron efficiency of better than 60%. Frequency tuning in steps of around 2–3 GHz might be needed for control of plasma stability. Multi-purpose operation at frequencies with leaps of about 30 GHz might be considered for plasma start-up, heating and current drive at different operation scenarios. The combination of those requirements clearly challenges present-day technological limits. The R&D work within the EUROfusion WP HCD EC Gyrotron R&D and Advanced Developments is focusing on named targets. In particular, a centre frequency of around 240 GHz is under investigation. The coaxial-cavity gyrotron technology, and, as a possible fallback solution, the conventional hollow-cavity are under investigation. Both options are studied with regards to maximum achievable output power versus efficiency, operation stability and tolerances. Concerning the coaxial-cavity technology, an additional experimental investigation shall verify the predicted operation capabilities. Various promising concepts for multi-stage depressed collectors (MSDC) are under investigation. The research and development are completed by advancing the simulation and test tools capabilities significantly. © 2017 The Authors

We report on the inhibitory activity of the NSAIDs meloxicam, carprofen, phenylbutazone and flunixin, on blood cyclooxygenases in the horse using in vitro enzyme-linked assays. As expected, comparison of IC50 indicated that meloxicam and carprofen are more selective inhibitors of COX-2 than phenylbutazone and flunixin; meloxicam was the most advantageous for horses of four NSAIDs examined. However at IC80, phenylbutazone (+134.4%) and flunixin (+29.7%) had greater COX-2 selectivity than at IC50, and meloxicam (-41.2%) and carprofen (-12.9%) had lower COX-2 selectivity than at IC50. We therefore propose that the selectivity of NSAIDs should be assessed at the 80% as well as 50% inhibition level.

The scaphoid is the most commonly fractured carpal bone, and preferable treatment of undisplaced fractures is controversial. In order to assess the socio-economic impact of treatment modalities, we analysed the cost of conservative management of 54 undisplaced scaphoid fractures. Global costs amounted to 14.077 Swiss francs (9385 euros) per patient. Direct costs represent only 10% of global costs. No significant correlation was found between costs and timing of diagnosis, hand dominance or complications. Thirty-four percent of patients were able to resume their job with the wrist immobilised without complication, but at an obvious impact on indirect and global costs. If early resumption of professional activities during conservative treatment of undisplaced scaphoid fractures does not impair successful fracture healing, patients should be encouraged to return to work as early as possible, as is routinely done after percutaneous fracture fixation. This will contribute to massively reducing the cost of conservative treatment.

In 1982, the European Organization for Research and Treatment of Cancer (EORTC) Radiotherapy Group established the Quality Assurance (QA) programme. During the past 20 years, QA procedures have become a major part of the activities of the group. The methodology and steps of the QA programme over the past 20 years are briefly described. Problems and conclusions arising from the results of the long-lasting QA programme in the EORTC radiotherapy group are discussed and emphasised. The EORTC radiotherapy group continues to lead QA in the European radiotherapy community. Future challenges and perspectives are proposed.

The European Organization for Research and Treatment of Cancer (EORTC) Radiotherapy Group initiated its mailed thermoluminescence dosimetry (TLD) programme in 1986. The aim of the present study was to evaluate the clinical relevance of variations in beam output detected in the period 1993 to 1996. A total of 140 beam outputs were checked (26 for cobalt-60 units and 114 for linear accelerators) in 35 centres. Clinical dose-response data for tumour control and normal tissue morbidity were used to assess the variation in clinical outcome resulting from variability in beam output. For 75 checked beams with nominal accelerating potentials (n. a.p.) of 6 MV or less the mean ratio, +/- standard deviation (S.D.) of measured to stated output was 1.004+/-0.020. For 65 beams with n. a.p. of 8 MV or more, the ratio was 1.009+/-0.021. Even with this relatively high level of precision, broad distributions of estimated tumour control or normal tissue morbidity were found. In the 10% of the beams with the most pronounced underdosage, the loss in tumour control probability was estimated at 7-8 percentage points. Likewise, in the 10% of the beams with the most pronounced overdosage, the increase in mild/moderate morbidity was 19-22 percentage points. For severe morbidity the same beams raised the estimated incidence of severe complications from 5% to 9-10%. An estimation of the loss of uncomplicated cure probability was about 1% for both high and low energy beams. Sequential mailings considerably improved the uniformity of clinical outcome. We conclude that small deviations in beam output may lead to clinically important variations in outcome. Substantial reductions in the variation between measured and stated output can be achieved by sequential mailings. Mailed TLD checks should be an integral part of a continuously ongoing quality assurance activity in radiotherapy.

Wedge factor ( WF ) variation with field size and depth has been analysed for 6 and 15 MV X-ray beams. The measured field size effect is 1.4% in the worst case, whereas the WF shows a linear dependence with depth giving a maximum variation of 0.22%/cm (60 ° wedge, 6 MV beam). An empirical correction for WF depth dependence on wedge thickness is proposed.

The results of a dummy run involving nine centers participating in a study comparing radiotherapy alone with radiotherapy plus hormone therapy in patients with high metastatic risk prostatic cancer (EORTC protocol 22863) show that, in all centers but one, patients are treated in the same way. However, they have also indicated that protocol compliance could be improved by a better assessment of the target volume, by taking into account of the use of protective shields and of variations in radiological density, by determining beam position on a large number of slices, and by the use of CT scan images for treatment planning.

The concept of a Master Protocol for phase III studies was raised at the Steering Committee of the EORTC Radiotherapy Group, in order to make the work of the study coordinators easier, when writing protocols and to give them more homogeneity. The Master Protocol defines and clarifies in a logical order the different steps which must be taken when designing a randomized trial - from the rationale to the references. It pays particular attention to eligibility criteria, volumes of interest defined in agreement with ICRU Report 50 (gross tumor volume, clinical target volume, planning target volume and organs at risk), simulation procedure, treatment technique, normal tissue sparing, dose computation, equipment, dose specification (also in agreement with ICRU Report 50). Last but not least, the different procedures of quality assurance for protocols and patients are also defined (site visits, dummy run procedure, in vivo dosimetry, individual case review) to allow working plans to be made in advance. We are aware that this work is not exhaustive, but hope that the contents will be of help to those who are writing a protocol.

Using a cell adhesion matrix monolayer culture system, we assayed the intrinsic radiosensitivity of 108 biopsies or surgical specimens of head and neck, colo-rectum, or cervix uteri carcinomas. After irradiating single cell suspensions with increasing doses (0–4 Gy), surviving fractions at 2 Gy (SF-2), initial slope α were estimated after a linear quadratic fitting of the curves. For cultures from biopsies or surgical specimens of head and neck carcinomas, the overall success rate was 65%. The pattern of the causes of failure for mass cultures was similar in other institutions investigating intrinsic radiosensitivity of squamous cell carcinomas. Within the same anatomic site and histological type, rumors were characterized by a wide range of in vitro radiosensitivity. In a series of 28 patients with head and neck cancers, the mean and standard deviation values of SF-2 were 0.30 ± 0.34. Likewise, α coefficients had an average of 0.61 ± 0.96 Gy−1. Cultures from colo-rectal cancers seem to have a higher mean level of intrinsic radioresistance (mean SF-2 = 0.49) than that of cells from head and neck tumors. Papanicolaou (PAP) staining and immuno-chemistry studies using monoclonal antibodies showed that stromal expression was a major problem for techniques using pre-coated plates. Nevertheless, the pattern of cumulative distribution of SF-2 values is not significantly different for cultures characterized by fibroblast overgrowth. In conclusion, notwithstanding variations in fibroblast growth, the comparative analysis of data published so far on intrinsic radiosensitivity shows that similar distributions of individual survival parameter values are yielded in the laboratories involved in this research field. Nevertheless, further studies on culture characterization, using monoclonal antibodies and flow cytometry, should be carried out to quantify better the impact of fibroblast contamination on culture response to irradiation. © Wiley-Liss, Inc.

A consensus on a quality assurance programme of the treatment of early breast cancer was reached in a multidisciplinary meeting of surgeons, pathologists, radiotherapists, physicists and radiographers. Guidelines for treatment preparation and execution have been set up, including careful location and excision with marking of the primary tumour. The target volumes for irradiation of the whole breast and boost area have been defined. Radiation dose prescription rules, specification and checking procedures are given, together with measures to achieve a homogeneous dose within the target volume. The rules for a quality assurance programme in each clinic are designed for checking equipment and treatment method.

Autologous chondrocyte implantation (ACI) is a frequently used procedure for full-thickness cartilage lesions in the knee joint. However, to date, there are just a few prospective, randomized clinical studies and most publications are case series on small and heterogenic cohorts with short-term follow-up. To date, ACI is a surgical treatment option for single traumatic lesions on the distal femur in young active subjects with a recent lesion. Lesion size should be between 3 and 8 cm2,6 mm in depth, tidemark preserved without penetration of the subchondral bone. Absolute contraindications for ACI include osteoarthrosis, kissing lesions, lesions size greater than 10 cm2 or deeper than 8 mm, ligament instability, partial or total meniscectomy, axis malalignment5. Further studies are mandatory to determine the precise indications to the technique and to show its superiority on the established treatment of chondral lesions.

Evaluation of diagnostic accuracy of high-spatial-resolution sonography (HSR-S) in occult scaphoid fractures.HSR-S was performed in 24 patients with clinically suspected fracture and normal radiographs. Three levels of clinical suspicion were considered (high, intermediate, and low). Three levels of sonographic suspicion were defined on the basis of cortical interruption, radiocarpal effusion, and scapho-trapezium-trapezoid effusion. Three positive criteria were interpreted as being highly indicative of fracture. Data from sonograms were compared with computed tomography (CT) scans.CT scanning demonstrated a fracture of the scaphoid in five patients. The global sensitivity of HSR-S for detection of occult scaphoid fracture was 100% and the specificity 79%. All patients with demonstrated occult fracture had a high sonography index of suspicion. A high sonography index of suspicion was correlated with 100% sensitivity, specificity, positive predictive value, and negative predictive value.HSR-S is a reliable, available, and cost-effective method in early diagnosis of occult fractures of the scaphoid. The presence of three defined criteria is required to assess the diagnosis.

In 1982, the European Organization for Research and Treatment of Cancer (EORTC) Radiotherapy Group established the Quality Assurance (QA) programme. During the past 20 years, QA procedures have become a major part of the activities of the group. The methodology and steps of the QA programme over the past 20 years are briefly described. Problems and conclusions arising from the results of the long-lasting QA programme in the EORTC radiotherapy group are discussed and emphasised. The EORTC radiotherapy group continues to lead QA in the European radiotherapy community. Future challenges and perspectives are proposed.

The safe application of ionising radiation for diagnosis and therapy requires a high level of knowledge of the underlying processes and of quality assurance. Sophisticated modern equipment can be used effectively for complicated diagnostic and therapeutic techniques only with adequate physics support. In the light of recent analyses and recommendations by national and international societies a joint working group of representatives from ESTRO (European Society for Therapeutic Radiology and Oncology) and from EFOMP (European Federation of Organisations for Medical Physics) was set up to assess the necessary staffing levels for physics support to radiotherapy. The method used to assess the staffing levels, the resulting recommendations and examples of their practical application are described.

In recent years, numerous publications have shown the feasibility and usefulness of in vivo dosimetry as an essential tool of quality assurance programs in radiotherapy [ 1,3,6,11]. In the context of this meeting on high dose/high precision radiotherapy, the presentations and discussions on in vivo dosimetry centred on its value for investigating the quality of specific treatment techniques: accuracy and reproducibility in dose delivery, benchmark role of in vivo dosimetyy, frequency of in vivo measurements and action levels for corrective actions.

A consensus on a quality assurance programme of the treatment of early breast cancer was reached in a multidisciplinary meeting of surgeons, pathologists, radiotherapists, physicists and radiographers. Guidelines for treatment preparation and execution have been set up, including careful location and excision with marking of the primary tumour. The target volumes for irradiation of the whole breast and boost area have been defined. Radiation dose prescription rules, specification and checking procedures are given, together with measures to achieve a homogeneous dose within the target volume. The rules for a quality assurance programme in each clinic are designed for checking equipment and treatment method.

ADPKD is the most widespread genetic nephropathy. Only twenty-five per cent of patients are symptomatic. In order to prevent the disease it is important early screening by ultrasonography that shows a typical picture only in adults. Familiar history is determinant for diagnosis in intrauterine age, in newborns and in infants. Ultrasonographic diagnosis is certain only after twenty-five weeks of pregnancy.

In 111 patients with essential hypertension (World Health Organization stage I or II), we examined the relationship between renal hemodynamics and left ventricular hypertrophy. Left ventricular structure was determined by two-dimensional guided M-mode echocardiography, renal blood flow by iodine I 131 aminohippuric acid clearance, and glomerular filtration rate by creatinine clearance. The glomerular filtration rate correlated with left ventricular mass (r = .52) and left ventricular cross-sectional area (r = .21). Conversely, at a similar age, body mass index, body surface area, and arterial pressure, hypertensive patients with left ventricular hypertrophy disclosed a higher glomerular filtration rate and filtration fraction than those without left ventricular hypertrophy, whereas renal blood flow and renal vascular resistance measurements were not significantly different. Thus, at similar levels of arterial pressure and renal blood flow, glomerular hyperfiltration was linked to early cardiac structural changes in essential hypertension. We conclude that, in a hypertensive patient with normal renal function, a high glomerular filtration rate may be an indicator for early target organ damage in essential hypertension.

The central nervous system of young children is particularly sensitive to neurological damage due to excessive lead exposure. The lead stored in a tooth is permanent and related to the quantity of ingested lead. The lead is assayed by measuring the characterisitc radiation from lead in a tooth in situ irradiated with gamma rays from a cobalt-57 source. The sensitivity of the method is adequate to measure lead levels commonly associated with environmental background. The X-ray exposure to the tooth necessary for this determination is approximately one tenth of that required for a routine dental examination.

Hyperlipoproteinemia was found in 200 patients affected by chronic renal failure on maintenance hemodialysis, due to increase in Total Cholesterol, VLDL-TG, LDL, TG, LDL and VLDL. In 30 of these patients, the analysis was extended to the dosing of decreased Total Serum HDL-Cholesterol, HDL2, HDL3, Apoprotein A and Apoprotein A1 values, and of increased Apoprotein B values. These findings further contribute to proving accelerated atherogenesis in the patients examined.

Cardiac performance, as judged by preload, afterload, and myocardial contractility, was evaluated by non-invasive M-mode echocardiography before and after acute oral administration of calcium entry blockers (nitrendipine and verapamil), angiotensin converting enzyme (ACE) inhibitors (captopril and lisinopril), and a dopamine receptor agonist (fenoldopam) in patients with mild to moderate essential hypertension. Left ventricular end diastolic volume was taken as an index of preload, end systolic stress as an index of afterload, and the ratio of systolic pressure to end systolic volume (SBP:ESV), ejection fraction (EF), and mean velocity of circumferential fibre shortening (Vcf) as indices of contractility. Reductions of afterload and mean arterial pressure were achieved with all antihypertensive agents involved (mean percentage change +/- s.e.m.: 15 +/- 2% and 10 +/- 1%, respectively, P0.05) but the afterload reduction with lisinopril was greatest (21 +/- 9%; P0.01). The dopamine receptor agonist fenoldopam decreased by preload 24% (P0.05) and increased all of the three parameters of myocardial contractility (SBP:SV 66%; EF 17%, Vcf 19%; P0.01). In contrast, no effect on these parameters was observed with either calcium entry blocker or either ACE inhibitor.