Radiological protection in ion beam radiotherapy: practical guidance for clinical use of new technology.

Recently introduced technologies in radiotherapy have significantly improved the clinical outcome for patients. Ion beam radiotherapy, involving proton and carbon ion beams, provides excellent dose distributions in targeted tumours, with reduced doses to the surrounding normal tissues. However, careful treatment planning is required in order to maximise the treatment efficiency and minimise the dose to normal tissues. Radiation exposure from secondary neutrons and photons, particle fragments, and photons from activated materials should also be considered for radiological protection of the patient and medical staff. Appropriate maintenance is needed for the equipment and air in the treatment room, which may be activated by the particle beam and its secondary radiation. This new treatment requires complex procedures and careful adjustment of parameters for each patient. Therefore, education and training for the personnel involved in the procedure are essential for both effective treatment and patient protection. The International Commission on Radiological Protection (ICRP) has provided recommendations for radiological protection in ion beam radiotherapy in Publication 127 Medical staff should be aware of the possible risks resulting from inappropriate use and control of the equipment. They should also consider the necessary procedures for patient protection when new technologies are introduced into clinical practice.

Phase I/II trial of definitive carbon ion radiotherapy for prostate cancer: evaluation of shortening of treatment period to 3 weeks.

BACKGROUND: The purpose of this study was to evaluate the feasibility of a new shortened 3-week treatment schedule of carbon ion radiotherapy (CIRT) for prostate cancer. METHODS: Beginning in May 2010, patients with T1b-T3bN0M0, histologically proven prostate adenocarcinoma were enrolled in the phase II trial of CIRT. Patients received 51.6 GyE in 12 fractions over 3 weeks (protocol 1002). The primary end point was defined as the incidence of late adverse events that were evaluated based on the Common Terminology Criteria for Adverse Events version 4.0. Biochemical failure was determined using the Phoenix definition (nadir +2.0 ng ml(-1)). RESULTS: Forty-six patients were enrolled, and all patients were included in the analysis. The number of low-, intermediate-, and high-risk patients was 12 (26%), 9 (20%), and 25 (54%), respectively. The median follow-up period of surviving patients was 32.3 months. Two patients had intercurrent death without recurrence, and the remaining 44 patients were alive at the time of this analysis. In the analysis of late toxicities, grade 1 (G1) rectal haemorrhage was observed in 3 (7%) patients. The incidence of G1 haematuria was observed in 6 (13%) patients, and G1 urinary frequency was observed in 17 (37%) patients. No ⩾G2 late toxicities were observed. In the analysis of acute toxicities, 2 (4%) patients showed G2 urinary frequency, and no other G2 acute toxicities were observed. CONCLUSIONS: The new shortened CIRT schedule over 3 weeks was considered as feasible. The analysis of long-term outcome is warranted.

ICRP Publication 127: Radiological Protection in Ion Beam Radiotherapy.

Abstract ­: The goal of external-beam radiotherapy is to provide precise dose localisation in the treatment volume of the target with minimal damage to the surrounding normal tissue. Ion beams, such as protons and carbon ions, provide excellent dose distributions due primarily to their finite range, allowing a significant reduction of undesired exposure of normal tissue. Careful treatment planning is required for the given type and localisation of the tumour to be treated in order to maximise treatment efficiency and minimise the dose to normal tissue. Radiation exposure in out-of-field volumes arises from secondary neutrons and photons, particle fragments, and photons from activated materials. These unavoidable doses should be considered from the standpoint of radiological protection of the patient. Radiological protection of medical staff at ion beam radiotherapy facilities requires special attention. Appropriate management and control are required for the therapeutic equipment and the air in the treatment room that can be activated by the particle beam and its secondaries. Radiological protection and safety management should always conform with regulatory requirements. The current regulations for occupational exposures in photon radiotherapy are applicable to ion beam radiotherapy with protons or carbon ions. However, ion beam radiotherapy requires a more complex treatment system than conventional radiotherapy, and appropriate training of staff and suitable quality assurance programmes are recommended to avoid possible accidental exposure of patients, to minimise unnecessary doses to normal tissue, and to minimise radiation exposure of staff.

Quantitative autistic traits ascertained in a national survey of 22 529 Japanese schoolchildren.

OBJECTIVE: Recent epidemiologic studies worldwide have documented a rise in prevalence rates for autism spectrum disorders (ASD). Broadening of diagnostic criteria for ASD may be a major contributor to the rise in prevalence, particularly if superimposed on an underlying continuous distribution of autistic traits. This study sought to determine the nature of the population distribution of autistic traits using a quantitative trait measure in a large national population sample of children. METHOD: The Japanese version of the Social Responsiveness Scale (SRS) was completed by parents on a nationally representative sample of 22 529 children, age 6-15. RESULTS: Social Responsiveness Scale scores exhibited a skewed normal distribution in the Japanese population with a single-factor structure and no significant relation to IQ within the normal intellectual range. There was no evidence of a natural 'cutoff' that would differentiate populations of categorically affected children from unaffected children. CONCLUSION: This study provides evidence of the continuous nature of autistic symptoms measured by the SRS, a validated quantitative trait measure. The findings reveal how paradigms for diagnosis that rest on arbitrarily imposed categorical cutoffs can result in substantial variation in prevalence estimation, especially when measurements used for case assignment are not standardized for a given population.

Effect of dietary Rhodobacter capsulatus on lipid fractions and egg-yolk fatty acid composition in laying hens.

The present study was conducted to investigate the effect of dietary Rhodobacter capsulatus on lipid fractions and egg-yolk fatty acid composition in laying hens. Thirty-six laying hens (30 weeks old) were randomly assigned into two dietary groups fed diets with (0.04%) or without (control) R. capsulatus for a 60-day feeding trial. Dietary R. capsulatus decreased (p < 0.05) serum and hepatic cholesterol and increased (p < 0.05) the excreta cholesterol, and resultant lower (p < 0.05) cholesterol contents in egg yolk. The concentration of polyunsaturated fatty acids (PUFA) and ratio to saturated fatty acids in egg yolk was improved (p < 0.05) by dietary R. capsulatus. The concentration of hepatic bile acid was increased (p < 0.05) and excreta bile acid was decreased (p < 0.01) in the laying hens fed R. capsulatus diet. The incorporation of 1-(14) C-palmitic acid into hepatic lipids and lipid fractions was increased (p < 0.05) in laying hens fed R. capsulatus diet. Moreover, dietary R. capsulatus did not appear to cause any adverse effects on laying hen performances. Therefore, dietary supplementation of R. capsulatus in layer diets may be a feasible means of producing eggs with lower cholesterol and higher PUFA contents for health conscious consumers.

Intracellular signaling cascades induced by relaxin in the stimulation of capacitation and acrosome reaction in fresh and frozen-thawed bovine spermatozoa.

Relaxin is one of the 6-kDa peptide hormones, which acts as a pleiotropic endocrine and paracrine factor. Our previous studies revealed that sperm capacitating medium containing relaxin induced capacitation and acrosome reaction (AR) in fresh and frozen-thawed porcine or bovine spermatozoa. However, the intracellular signaling cascades involved with capacitation or AR induced by relaxin was unknown. Therefore, the present study was designed to investigate the intracellular signaling cascades involved with capacitation and AR induced by relaxin in fresh and frozen-thawed bovine spermatozoa. Spermatozoa were incubated in sperm Tyrode's albumin lactate pyruvate (Sp-TALP) medium supplemented with (40 ng ml(-1)) or without relaxin, and subjected to evaluation of chlortetracycline staining pattern, cholesterol efflux, Ca(2+)-influx, intracellular cyclic adenosine monophosphate (cAMP) and protein tyrosine phosphorylation. Capacitation and AR were increased (P<0.05) in both fresh and frozen-thawed spermatozoa incubated with relaxin. Cholesterol effluxes were greater in the fresh (P<0.01) and frozen-thawed (P<0.05) spermatozoa incubated with relaxin than the spermatozoa incubated without relaxin. Ca(2+)-influxes were also significantly stimulated by relaxin in the fresh (P<0.01) and frozen-thawed (P<0.05) spermatozoa. The Sp-TALP medium containing relaxin influenced the generation of intracellular cAMP in the fresh (P<0.01) and frozen-thawed (P<0.05) spermatozoa, and exhibited higher exposure of protein tyrosine phosphorylation in both sperm types than the medium devoid of relaxin. Therefore, the results postulate that relaxin exerts the intracellular signaling cascades involved with capacitation and AR through accelerating the cholesterol efflux, Ca(2+)-influx, intracellular cAMP and protein tyrosine phosphorylation in fresh and frozen-thawed bovine spermatozoa.

Carbon ion radiotherapy for sacral chordoma.

The National Institute of Radiological Sciences in Chiba, Japan has offered carbon ion radiotherapy (CIRT) since 1994 using carbon ion beams generated by the heavy ion medical accelerator in Chiba (HIMAC). The total number of cases treated with the HIMAC exceeded 5000 in July 2009. Here, we present a retrospective analysis of CIRT for sacral chordoma. The study included 95 patients with medically unresectable sacral chordomas treated between 1996 and 2007. The median age of the patients was 66 years. Of all the patients, 84 had not been treated previously and 11 had a locally recurrent tumour following previous resection. The carbon ion dose ranged from 52.8 to 73.6 GyE (median 70.4 GyE) in a total of 16 fixed fractions over 4 weeks. The median clinical target volume was 370 cm(3). The overall survival rate at 5 years for all 95 patients was 86%, and follow-up survival time was 42 months (range, 13-112 months). The 5-year local control rate was 88% and median time to local failure was 35 months (range, 13-60 months). Of the 95 patients, 91% remained ambulatory with or without a supportive device. Two patients experienced severe skin or soft tissue complications requiring skin grafts. 15 patients experienced severe sciatic nerve complications requiring continuing medication. CIRT appears effective and safe in the management of patients with sacral chordoma and offers a promising alternative to surgery.

Hypocholesterolemic effect of karaya saponin in Japanese laying quails (Coturnix coturnix japonica).

The effect of karaya saponin supplementation on the serum and egg yolk cholesterol and fatty acid composition in egg yolk were investigated in Japanese quails. A total of 80 Japanese quails aged 5 weeks were equally divided into four groups of 20. Four levels (0, 25, 50 and 75 mg/kg feed) of karaya saponin were included in the basal diet and experiment was lasted for 6 weeks. The cholesterol fractions in the egg yolk and serum were measured by enzymatic assay, and the fatty acid composition in egg yolk was determined by gas chromatography. The results revealed that the supplementation of 75 mg/kg karaya saponin significantly reduced (p < 0.05) cholesterol and triglycerides concentration in serum and egg yolk. High-density lipoprotein-cholesterol was increased, low-density lipoprotein-cholesterol and the atherogenic index were decreased (p < 0.05) by the dietary supplementations. Hepatic cholesterol was reduced (p < 0.05) by the 25 mg/kg karaya saponin. A higher degree of yolk colour was improved (p < 0.05) when 75 mg/kg saponin was supplemented in the diet. The concentration of polyunsaturated fatty acids (PUFA) in egg yolk was increased (p < 0.05) in a dose-dependent manner in quails fed the supplemented diet than the control diet. The ratio of PUFA to saturated fatty acids in egg yolk was improved (p < 0.05) by 75 mg/kg feed karaya saponin-supplemented diet. Therefore, the dietary supplementation of 75 mg/kg karaya saponin may be a feasible means of producing quail eggs with lower cholesterol and higher PUFA content for health conscious consumers.

Effect of dietary karaya saponin on serum and egg yolk cholesterol in laying hens.

1. The objective of the study was to investigate the effect of dietary karaya saponin on cholesterol deposition in laying hens. 2. A total of 40 Boris Brown hens were randomly assigned at 20 weeks of age to 4 treatment groups and fed on diets supplemented with 0 (control), 25, 50 or 75 mg/kg karaya saponin for an 8-week experimental period. 3. After 8 weeks of dietary supplementation, karaya-saponin-treated groups had significantly lower serum cholesterol (23·0%) and triglycerides but increased high density lipoproteins cholesterol concentration than controls, irrespective of karaya saponin content in the diet. Egg yolk cholesterol and triglycerides were also significantly reduced by dietary karaya saponin. Hepatic cholesterol and triglycerides were significantly reduced by karaya saponin but bile acids concentration in the faeces and liver were significantly increased by karaya saponin. The concentrations of oleic, linoleic and linolenic acids in the yolk were greater in hens receiving karaya saponin than in controls. Karaya saponin significantly increased egg production, feed efficiency and yolk colour compared with controls. Karaya saponin tended to increase egg weight, feed consumption, Haugh units, albumen weight and yolk index. 4. In conclusion, karaya saponin is a potential agent for reducing yolk cholesterol concentration together with an overall increase of production performance and improvement in egg quality.

Effects of karaya saponin and Rhodobacter capsulatus on yolk cholesterol in laying hens.

1. It has been reported that karaya saponin and Rhodobacter capsulatus individually have hypocholesterolaemic activity in laying hens. This study focuses on the effect of adding karaya saponin with R. capsulatus to hen's diet with regard to serum and egg yolk cholesterol and triglycerides. 2. A total of 56 Boris Brown laying hens were divided into 7 groups at 20 weeks of age. Combinations of 25, 50, 75 mg kg(-1) karaya saponin and R. capsulatus 200 and 400 mg kg(-1) were used as treatment groups. 3. After 8 weeks of supplementation, the effects of all the combinations of karaya saponin and R. capsulatus on serum and egg yolk cholesterol, triglycerides, and high-density lipoprotein (HDL)-cholesterol were greater than either karaya saponin or R. capsulatus alone. The combination of karaya saponin 50 mg kg(-1)+ R. capsulatus 400 mg kg(-1) exhibited the greatest reduction of serum (325%) and yolk (225%) cholesterol and the greatest increase of faecal, liver bile acids and yolk fatty acid (oleic, linoleic and linolenic) concentrations. In addition, egg production and yolk colour were significantly improved by the combined use of karaya saponin and R. capsulatus supplementation. 4. Therefore, the dietary supplementation of karaya saponin and R. capsulatus may lead to the production of a low-cholesterol egg, with production performance maintained at a standard level.

Investigation of the heavy fermion state and superconductivity in Pr(1-x)La(x)Os4Sb12 by the upper critical field slope at Tc.

Measurements of the upper critical field H(c2) near T(c) of Pr(1 - x)La(x)Os(4)Sb(12) were performed by specific heat. The results support the hypothesis of a non-single-ion origin of m* enhancement in PrOs(4)Sb(12), derived from the analysis of the C/T discontinuity at T(c). Both sets of measurements indicate the existence of a crossover concentration, x(cr)≈0.2-0.3, separating heavy fermion-like alloys (x < x(cr)) from normal metals (x > x(cr)). Heavy fermion-like alloys exhibit field-induced long-range antiferro-quadrupolar (AFQ) anomalies in the specific heat, while those with x > x(cr) do not. The curvature in H(c2) versus T near T(c), observed in different measurements on pure PrOs(4)Sb(12), is sample- and method-dependent.

Rationale for carbon ion therapy in high-grade glioma based on a review and a meta-analysis of neutron beam trials.

PURPOSE: The standard treatment of high-grade glioma is still unsatisfactory: the 2-year survival after radiotherapy being only 10-25%. A high linear energy transfer (LET) ionising radiotherapy has been used to overcome tumour radioresistance. An overview of the field is needed to justify future prospective controlled studies on carbon ion therapy. MATERIALS AND METHODS: A meta-analysis of clinical trials on neutron beam therapy and a literature review of clinical investigations on light ion use in high-grade glioma were carried out. RESULTS: Four randomised controlled trials on neutron beam therapy were retained. The meta-analysis showed a non-significant 6% increase of two-year mortality (Relative risk [RR]=1.06 [0.97-1.15]) in comparison with photon therapy. Two phase I/II trials on carbon and neon ion therapy reported for glioblastoma 10% and 31% two-year overall survivals and 13.9 and 19.0 months median survivals, respectively. CONCLUSION: This meta-analysis suggests that neutron beam therapy does not improve the survival of high-grade glioma patients while there is no definitive conclusion yet regarding carbon therapy. The ballistic accuracy and the improved biological efficacy of carbon ions renew the interest in prospective clinical trials on particle beam radiotherapy of glioma and let us expect favourable effects of dose escalation on patients' survival.

Carbon-ion radiotherapy: clinical aspects and related dosimetry.

The features of relativistic carbon-ion beams are attractive from the viewpoint of radiotherapy. They exhibit not only a superior physical dose distribution but also an increase in biological efficiency with depth, because energy loss of the beams increases as they penetrate the body. This paper reviews clinical aspects of carbon-beam radiotherapy using the experience at the National Institute of Radiological Sciences. The paper also outlines the dosimetry related to carbon-beam radiotherapy, including absolute dosimetry of the carbon beam, neutron measurements and radiation protection measurements.

The dilute limit of heavy fermions: evidence of the coherent nature of CeAl(3).

Strongly diluted Ce(x)La(1-x)Al(3) alloys have been studied by the low temperature specific heat in order to elucidate the mechanism that determines their ground state. The results for alloys with Ce concentrations of 0.0005≤x≤0.1 are fairly consistent with a S = 1/2 Kondo behavior. However, the single-ion scaling is observed only below x = 0.01. The true single-ion Kondo temperature is small, 0.2 K, approximately equal to that for dilute CeAl(2). It is about 20 times smaller than that for CeAl(3), indicating the coherent nature of CeAl(3). The single-ion contribution to thermodynamic properties of CeAl(3) is negligible even at temperatures as high as 5 K.

Effect of glutathione on the development of rat embryos following microinsemination.

PURPOSE: The present study was carried out to evaluate the role of glutathione on rat embryo developmental potential after ICSI. We observed the effects of glutathione on the development of non-treated rat embryos, ICSI embryos and embryos with sham injection treatment. The development of glutathione-microinjected embryos was also observed. METHODS: Oocytes and fertilized embryos were obtained from superovulated Wistar-Imamichi rats and cultured in mR1ECM medium. Oocytes and embryos were then allowed to develop to assess the effect of glutathione on the development rate in intact embryos, micro-injected embryos and ICSI embryos. RESULTS: (1) In the intact embryo, the proportion of blastocyst stage development increased when 0.01 mM GSH was added to the medium compared to the control. (2) Microinjection of glutathione (GSSG, GSH) into the embryo increased development at each stage, and the addition of 0.2 nM GSSG or GSH significantly increased blastocyst development, in comparison to that of the control (P < 0.05). (3) Compared to the control, all the GSSG and GSH concentrations improved damaged blastocyst development, where 0.01 mM GSH improved significantly (P < 0.05). (4) The addition of glutathione in the medium increased the rate of blastocyst development after ICSI. A significantly higher number of TE and total cells were obtained in the micro-injected embryo with both of the 0.02 mM GSSG and GSH treatments (P < 0.05). CONCLUSIONS: The addition of glutathione into the culture media can improve early embryo development and is capable of repairing the damage of ICSI rat embryos.

The beneficial effect of fructose and glucose on in vitro maturation and the fertilization of porcine oocytes.

PURPOSE: This study was conducted to investigate the effects of supplementing fructose in the culture medium on in vitro maturation (IVM), in vitro fertilization (IVF), and metabolism of porcine oocytes. METHODS: Porcine oocytes were matured in vitro in modified North Carolina State University 37 medium (NCSU-37) and then supplemented with either glucose (5.5 mM), fructose (5.5 mM), or glucose (2.75 mM) plus fructose (2.75 mM). The maturation and fertilization of oocytes, and the incorporation and oxidation of 14C-glucose, 14C-fructose, and 14C-methionine in oocytes at different stages of development were examined. RESULTS: The supplementation of glucose plus fructose significantly promoted (P < 0.05) oocytes germinal vesicle break down (GVBD), maturation to metaphase II (MII), penetration by spermatozoa, and male pronuclear formation compared with glucose. The incorporation and oxidation of 14C-methionine into the oocyte significantly increased (P < 0.05) with glucose plus fructose supplementation than glucose. A significantly higher (P < 0.05) rate of incorporation and oxidation was achieved with 14C-fructose compared to 14C-glucose. CONCLUSIONS: Glucose plus fructose supplementation improved maturation, penetration by spermatozoa, male pronuclear formation, and energy metabolism by porcine oocytes.

Novel quantum criticality in CeRu2Si2 near absolute zero observed by thermal expansion and magnetostriction.

We report linear thermal expansion and magnetostriction measurements for CeRu2Si2 in magnetic fields up to 52.6 mT and at temperatures down to 1 mK. At high temperatures, this compound showed Landau-Fermi-liquid behavior: The linear thermal expansion coefficient and the magnetostriction coefficient were proportional to the temperature and magnetic field, respectively. In contrast, a pronounced non-Fermi-liquid effect was found below 50 mK. The negative contribution of thermal expansion and magnetostriction suggests the existence of an additional quantum critical point.

Comparison between 3-D and z-axis automatic tube current modulation technique in multidetector-row CT.

In this study, the 3-D automatic tube current modulation (3-D ATCM) technique was compared with the z-axis ATCM technique on multidetector-row CT. Absorbed dose measurements were performed by inserting an ion chamber into the phantoms, and objective image noise shown as the standard deviation of CT value in Hounsfield units was measured on the obtained images. The ratio of absorbed doses with 3-D ATCM technique to z-axis ATCM technique was 94.7% using an elliptical cylinder phantom with an inner cylinder phantom and 96.3% using an elliptical cylinder phantom without an inner cylinder phantom. Differences in objective noise between the 3-D ATCM technique and z-axis ATCM technique were within a tolerable range compared with the setting noise index. Therefore, the 3-D ATCM technique effectively optimises the radiation dose, while maintaining an appropriate image quality compared with z-axis ATCM technique.

Effect of dietary Rhodobacter capsulatus on cholesterol concentration and fatty acid composition in broiler meat.

The study was designed to investigate the effects of dietary Rhodobacter capsulatus on cholesterol concentration and fatty acid composition in broiler meat. A total of 45 two-week-old male broiler chicks were randomly assigned into 3 treatment groups and fed ad libitum diets supplemented with 0 (control), 0.02, and 0.04% R. capsulatus for a 6-wk feeding period. The results of this study revealed that the supplementation of 0.04% R. capsulatus in diet reduced (P < 0.05) cholesterol and triglyceride concentrations in broiler meat. The concentrations (expressed as a percentage of total fatty acids) of oleic acid (18:1), linoleic acid (18:2), and linolenic (18:3) acid in thigh muscle and breast muscle were higher (P < 0.05) in the broilers fed the 0.04% R. capsulatus supplemented diet than in the broilers fed the control diet. The ratio of unsaturated fatty acids to saturated fatty acids was greater (P < 0.05) in both muscles of broilers fed the 0.04% R. capsulatus supplemented diet than the control diet. In addition, the concentrations of serum cholesterol and triglyceride, and hepatic cholesterol and triglyceride were also reduced (P < 0.05) by dietary R. capsulatus. Compared with the control diet, the 0.04% R. capsulatus supplemented diet reduced (P < 0.05) the ratio of low-density lipoprotein-cholesterol to high-density lipoprotein-cholesterol. Moreover, the supplementation of R. capsulatus in broiler diets did not show any adverse effect on production performance. Therefore, these results conclude that the application of R. capsulatus into diet may be feasible to reduce cholesterol concentration and improve the ratio of unsaturated fatty acids to saturated fatty acids in broiler meat.

Carbon ion radiotherapy for vaginal malignant melanoma: a case report.

Malignant melanoma of the vagina is a very rare neoplasm and resistant to conventional radiotherapy. We report a case of vaginal malignant melanoma that was locally well controlled by carbon ion radiotherapy. A 55-year-old postmenopausal woman presented with abnormal vaginal bleeding. On pelvic and imaging examinations, an irregular mass of the posterior vaginal wall sized 7.5 x 5 x 5 cm, an enlarged right inguinal lymph node, and two lung metastases were observed. Histologic diagnosis based on positive immunostaining for HMB-45 was malignant melanoma. She received dacarbazine-based chemotherapy and carbon ion radiotherapy for vaginal and inguinal tumor sites with 57.6 Gy equivalent dose per 16 fractions using five ports. Six months later, she was also given carbon ion radiotherapy for regrowing lung metastasis with 52.8 Gy equivalent dose per four fractions using four ports. She died 19 months after initial treatment due to brain metastases. The primary irradiated tumor disappeared completely 12 months after initial treatment. The vaginal tumor, right inguinal lymph node, and lung tumor treated with carbon ion radiotherapy did not show any evidence of recurrence until her death. Carbon ion radiotherapy may be of value for vaginal malignant melanoma as a conservative approach.