Typical Dose Research Articles

Detecting demineralization of enamel and cementum after gamma irradiation using radiographic densitometry.

The purpose of this study was to evaluate the ability of radiographic densitometry in detecting the early demineralization of human enamel and cementum in irradiated and non-irradiated teeth. Sixty extracted teeth were divided into two groups: irradiated group and non-irradiated group. After irradiation, the groups were subjected to demineralization-remineralization (PH) cycling. Radiographic densitometric measurements (gray values) of a selected area of interest in the enamel and in the cementum of each tooth were performed at baseline and after PH cycling. After PH cycling, there was a significant reduction in gray values for both groups. The difference between "baseline" and "after PH cycling" values represents the reduction in the mineral content of the hard tissue, i.e., the demineralization. Results show that the demineralization of irradiated tooth enamel and cementum was significantly higher compared to that of non-irradiated tissues as determined by gray-level values. It is concluded that densitometric measurements by means of digital radiographs allow for the detection of demineralization of enamel and cementum, and can be used successfully for diagnosis of the early carious lesions in patients who received head and neck radiotherapy. This will allow implementation of remineralizing therapy and avoid the risk of progression of radiation caries. Furthermore, it is concluded that gamma irradiation with typical therapeutic doses for head and neck carcinoma is a direct cause of demineralization of tooth enamel and cementum.

Method for Real-Time Tissue Quantification of Indocyanine Green Revealing Optimal Conditions for Near Infrared Fluorescence Guided Surgery.

Near infrared fluorescence guided surgery (NIRFGS) offers better distinction between cancerous and normal tissues compared to surgeries relying on a surgeon's senses of sight and touch. Because of the greater accuracy in determining tumor tissue margins, NIRFGS within clinics continues to grow. However, NIRFGS lacks standardization of the indocyanine green (ICG) dose and the preoperative period allowed after ICG administration. In an aim to find optimal doses and preoperative periods for NIRFGS standardization, we developed a method that quantitatively determines ICG levels within tissues in real-time. We find that not only do the dose and the preoperative periods influence tumor-to-background ratios (TBRs), but both also heavily influence subject-to-subject variances of these ratios. Optimal detection conditions are observed when larger than typical ICG doses are administered and longer than typical preoperative periods are allowed. Larger doses lead to increased TBRs, but longer preoperative periods are necessary to reduce TBR variances to those observed when using smaller doses. Our results suggest that a clinical investigation into maximum tolerable ICG doses and prolonging preoperative periods in NIRFGS is warranted.

Study of radiotoxic 210Po in Indian tobacco using liquid scintillation spectrometry

Abstract A fast radioanalytical method has been developed to measure 210Po in tobacco samples. After microwave digestion polonium is extracted quantitatively from a 1 M hydrochloric acid solution into a solution of triisooctylamine in toluene. The extract was measured by liquid scintillation counting in α mode. Caused by the high counting efficiency the counting time per sample can be reduced significantly compared to conventional α spectrometry, allowing for high sample throughput. The method was applied to 11 brands of cigarettes, beedis and or chewing tobaccos from India. Based on the resulting activity concentrations and typical consumption habits, annual and lifetime equivalent doses were calculated. They were found to be ~100–700 μSv/a or ~5–35 mSv, respectively.

Recombinant Tissue Plasminogen Activator-conjugated Nanoparticles Effectively Targets Thrombolysis in a Rat Model of Middle Cerebral Artery Occlusion.

The efficacy and safety of recombinant tissue plasminogen activator (rtPA) need to be improved due to its low bioavailability and requirement of large dose administration. The purpose of this study was to develop a fibrin-targeted nanoparticle (NP) drug delivery system for thrombosis combination therapy. We conjugated rtPA to poly(ethylene glycol)- poly(e-caprolactone) (PEG-PCL) nanoparticles (rtPA-NP) and investigated its physicochemical characteristics such as particle size, zeta potential, enzyme activity of conjugated rtPA and its storage stability at 4°C. The thrombolytic activity of rtPA-NP was evaluated in vitro and in vivo as well as the half-life of rtPA-NP, the properties to fibrin targeting and its influences on systemic hemostasis in vivo. The results showed that rtPA-NP equivalent to 10% of a typical dose of rtPA could dissolve fibrin clots and were demonstrated to have a neuroprotective effect after focal cerebral ischemia as evidenced by decreased infarct volume and improved neurological deficit (P<0.001). RtPA-NP did not influence the in vivo hemostasis or coagulation system. The half-life of conjugated rtPA was shown to be approximately 18 times longer than that of free rtPA. These experiments suggested that rtPA-conjugated PEG-PCL nanoparticles might be a promising fibrin-targeted delivery system for a combination treatment of thrombosis.

Genomic and Transcriptomic Insights into How Bacteria Withstand High Concentrations of Benzalkonium Chloride Biocides.

Benzalkonium chlorides (BAC) are commonly used biocides in broad-spectrum disinfectant solutions. How microorganisms cope with BAC exposure remains poorly understood, despite its importance for disinfection and disinfectant-induced antibiotic resistance. To provide insights into these issues, we exposed two isolates of an opportunistic pathogen, Pseudomonas aeruginosa, to increasing concentrations of BAC. One isolate was preadapted to BAC, as it originated from a bioreactor fed with subinhibitory concentrations of BAC for 3 years, while the other originated from a bioreactor that received no BAC. Replicated populations of both isolates were able to survive high concentrations of BAC, up to 1,200 and 1,600 mg/liter for the non- and preadapted strains, respectively, exceeding typical application doses. Transcriptome sequencing (RNA-seq) analysis revealed upregulation of efflux pump genes and decreased expression of porins related to BAC transport as well as reduced growth rate. Increased expression of spermidine (a polycation) synthase genes and mutations in the pmrB (polymyxin resistance) gene, which cause a reduction in membrane negative charge, suggested that a major adaptation to exposure to the cationic surfactant BAC was to actively stabilize cell surface charge. Collectively, these results revealed that P. aeruginosa adapts to BAC exposure by a combination of mechanisms and provided genetic markers to monitor BAC-resistant organisms that may have applications in the practice of disinfection.IMPORTANCE BAC are widely used as biocides in disinfectant solutions, food-processing lines, domestic households, and health care facilities. Due to their wide use and mode of action, there has been rising concern that BAC may promote antibiotic resistance. Consistent with this idea, at least 40 outbreaks have been attributed to infection by disinfectant- and antibiotic-resistant pathogens such as P. aeruginosa However, the underlying molecular mechanisms that bacteria use to deal with BAC exposure remain poorly elucidated. Elucidating these mechanisms may be important for monitoring and limiting the spread of disinfectant-resistant pathogens. Using an integrated approach that combined genomics and transcriptomics with physiological characterization of BAC-adapted isolates, this study provided a comprehensive understanding of the BAC resistance mechanisms in P. aeruginosa Our findings also revealed potential genetic markers to detect and monitor the abundance of BAC-resistant pathogens across clinical or environmental settings. This work contributes new knowledge about high concentrations of benzalkonium chlorides disinfectants-resistance mechanisms at the whole-cell genomic and transcriptomic level.

Cardiac Structure Injury After Radiotherapy for Breast Cancer: Cross-Sectional Study With Individual Patient Data.

Purpose Incidental cardiac irradiation can cause cardiac injury, but little is known about the effect of radiation on specific cardiac segments. Methods For 456 women who received breast cancer radiotherapy between 1958 and 2001 and then later experienced a major coronary event, information was obtained on the radiotherapy regimen they received and on the location of their cardiac injury. For 414 women, all with documented location of left ventricular (LV) injury, doses to five LV segments were estimated. For 133 women, all with documented location of coronary artery disease with ≥ 70% stenosis, doses to six coronary artery segments were estimated. For each segment, numbers of women with left-sided and right-sided breast cancer were compared. Results Of women with LV injury, 243 had left-sided breast cancer and 171 had right-sided breast cancer (ratio of left v right, 1.42; 95% CI, 1.17 to 1.73), reflecting the higher typical LV radiation doses in left-sided cancer (average dose left-sided, 8.3 Gy; average dose right-sided, 0.6 Gy; left minus right dose difference, 7.7 Gy). For individual LV segments, the ratios of women with left- versus right-sided radiotherapy were as follows: inferior, 0.94 (95% CI, 0.70 to 1.25); lateral, 1.42 (95% CI, 1.04 to 1.95); septal, 2.09 (95% CI, 1.37 to 3.19); anterior, 1.85 (95% CI, 1.39 to 2.46); and apex, 4.64 (95% CI, 2.42 to 8.90); corresponding left-minus-right dose differences for these segments were 2.7, 4.9, 7.2, 10.4, and 21.6 Gy, respectively ( Ptrend < .001). For women with coronary artery disease, the ratios of women with left- versus right-radiotherapy for individual coronary artery segments were as follows: right coronary artery proximal, 0.48 (95% CI, 0.26 to 0.91); right coronary artery mid or distal, 1.69 (95% CI, 0.85 to 3.36); circumflex proximal, 1.46 (95% CI, 0.72 to 2.96); circumflex distal, 1.11 (95% CI, 0.45 to 2.73); left anterior descending proximal, 1.89 (95% CI, 1.07 to 3.34); and left anterior descending mid or distal, 2.33 (95% CI, 1.19 to 4.59); corresponding left-minus-right dose differences for these segements were -5.0, -2.5, 1.6, 3.5, 9.5, and 38.8 Gy ( Ptrend = .002). Conclusion For individual LV and coronary artery segments, higher radiation doses were strongly associated with more frequent injury, suggesting that all segments are sensitive to radiation and that doses to all segments should be minimized.

Monte Carlo study of out-of-field exposure in carbon-ion radiotherapy with a passive beam: Organ doses in prostate cancer treatment

PurposeThe aim of this work was to estimate typical dose equivalents to out-of-field organs during carbon-ion radiotherapy (CIRT) with a passive beam for prostate cancer treatment. Additionally, sensitivity analyses of organ doses for various beam parameters and phantom sizes were performed. MethodsBecause the CIRT out-of-field dose depends on the beam parameters, the typical values of those parameters were determined from statistical data on the target properties of patients who received CIRT at the Heavy-Ion Medical Accelerator in Chiba (HIMAC). Using these typical beam-parameter values, out-of-field organ dose equivalents during CIRT for typical prostate treatment were estimated by Monte Carlo simulations using the Particle and Heavy-Ion Transport Code System (PHITS) and the ICRP reference phantom. ResultsThe results showed that the dose decreased with distance from the target, ranging from 116 mSv in the testes to 7 mSv in the brain. The organ dose equivalents per treatment dose were lower than those either in 6-MV intensity-modulated radiotherapy or in brachytherapy with an Ir-192 source for organs within 40 cm of the target. Sensitivity analyses established that the differences from typical values were within ∼30% for all organs, except the sigmoid colon. ConclusionsThe typical out-of-field organ dose equivalents during passive-beam CIRT were shown. The low sensitivity of the dose equivalent in organs farther than 20 cm from the target indicated that individual dose assessments required for retrospective epidemiological studies may be limited to organs around the target in cases of passive-beam CIRT for prostate cancer.

Erythritol, at insecticidal doses, has harmful effects on two common agricultural crop plants.

Erythritol, a non-nutritive polyol, is the main component of the artificial sweetener Truvia®. Recent research has indicated that erythritol may have potential as an organic insecticide, given its harmful effects on several insects but apparent safety for mammals. However, for erythritol to have practical use as an insecticide in agricultural settings, it must have neutral to positive effects on crop plants and other non-target organisms. We examined the dose-dependent effects of erythritol (0, 5, 50, 500, 1000, and 2000 mM) on corn (Zea mays) and tomato (Solanum lycopersicum) seedling growth and seed germination. Erythritol caused significant reductions in both belowground (root) and aboveground (shoot) dry weight at and above the typical minimum insecticidal dose (500 mM erythritol) in tomato plants, but not in corn plants. Both corn and tomato seed germination was inhibited by erythritol but the tomato seeds appeared to be more sensitive, responding at concentrations as low as 50 mM erythritol (in contrast to a minimum damaging dose of 1000 mM erythritol for corn seeds). Our results suggest erythritol may have damaging non-target effects on certain plant crops when used daily at the typical doses needed to kill insect pests. Furthermore, if erythritol’s damaging effects extend to certain weed species, it also may have potential as an organic herbicide.

Effects of Vitamin B6 (Pyridoxine) and a B Complex Preparation on Dreaming and Sleep.

Anecdotal evidence indicates that supplementation with vitamin B6 (pyridoxine) before bed can enhance dream vividness and recall. In a single pilot study, Ebben, Lequerica, and Spielman (2002) found that vitamin B6 had a dose-dependent effect of increasing scores on a composite measure of dream vividness, bizarreness, emotionality, and color. The present research replicated this study using a larger and more diverse sample of 100 participants from across Australia. We conducted a randomized, double-blind, placebo-controlled investigation of the effects on dreaming and sleep of ingesting 240 mg vitamin B6 (pyridoxine hydrochloride) before bed for five consecutive days. We also included an exploratory condition involving a B complex preparation containing a range of B vitamins. We found that vitamin B6 significantly increased the amount of dream content participants recalled but did not significantly affect dream vividness, bizarreness, or color, nor did it significantly affect other sleep-related variables. In contrast, participants in the B complex group showed significantly lower self-rated sleep quality and significantly higher tiredness on waking. We discuss the potential for using vitamin B6 in research on lucid dreaming.

High doses of laser phototherapy can increase proliferation in melanoma stromal connective tissue.

It is well established that laser phototherapy (LP) is contraindicated directly over cancer cells, due to its bio modulatory effects in cell and blood vessel proliferation. The aim of the present study was to analyze the influence of typical low-level laser therapy (LLLT) and high intensity laser therapy (HILT) and an in-between dose of 9J on collagen fibers and blood vessels content in melanoma tumors (B16F10) implanted in mice. Melanoma tumor cells were injected in male Balb C mice which were distributed in four groups: control (no irradiated) or irradiated by 3, 9, or 21J (150; 450, or 1050J/cm2). LP was performed in daily sessions for 3days with a InGaAlP-660nm (mean output: 50mW, spot size: 2mm2). Tumor volume was analyzed using (1) picrosirius staining to quantify collagen fibers content and (2) Verhoeff's method to quantify blood vessels content. Tumor growth outcome measured in the 3-J group was not significantly different from controls. Nine and 21-J groups, presented significant and dose-dependent increases in tumor volume. Quantitative analysis of the intensity of collagen fibers and their organization in stroma and peri-tumoral microenvironment showed significant differences between irradiated and control group. Blood vessels count of 21-J group outnumbered the other groups. High doses (≥9J) of LP showed a dose-dependent tumor growth, different collagen fibers characteristics, and eventually blood vessel growth, while a typical LLLT dose (3J) appeared harmless on melanoma cell activity.

Short Drug-Light Intervals Improve Liposomal Chemophototherapy in Mice Bearing MIA PaCa-2 Xenografts.

Chemophototherapy (CPT) is an emerging tumor treatment that combines phototherapy and chemotherapy. Long-circulating (LC) liposomes can stably incorporate 2 mol % porphyrin-phospholipid (PoP) in the bilayer and load doxorubicin (Dox) to generate LC-Dox-PoP liposomes, for single-agent CPT. Following intravenous administration to mice, LC-Dox-PoP liposomes (2 mg/kg Dox) circulated with similar blood concentration ranges produced by a typical human clinical dose of DOXIL (50 mg/m2 Dox). This dosing approach aims to achieve physiologically relevant Dox and PoP concentrations as well as CPT vascular responses in mice bearing subcutaneous human pancreatic MIA PaCa-2 xenografts. Phototreatment with 2 mg/kg LC-Dox-PoP induced vascular permeabilization, leading to a 12.5-fold increase in Dox tumor influx estimated by a pharmacokinetic model, based on experimental data. Shorter drug-light intervals (0.5-3 h) led to greater tumoral drug deposition and improved treatment outcomes, compared to longer drug-light intervals. At 2 mg/kg Dox, CPT with LC-Dox-PoP liposomes induced tumor regression and growth inhibition, whereas chemotherapy using several other formulations of Dox did not. LC-Dox-PoP liposomes were well tolerated at the 2 mg/kg dose.

Ultraviolet radiation in the Atacama Desert.

The world's highest levels of surface ultraviolet (UV) irradiance have been measured in the Atacama Desert. This area is characterized by its high altitude, prevalent cloudless conditions, and a relatively low total ozone column. In this paper, we provide estimates of the surface UV (monthly UV index at noon and annual doses of UV-B and UV-A) for all sky conditions in the Atacama Desert. We found that the UV index at noon during the austral summer is expected to be greater than 11 in the whole desert. The annual UV-B (UV-A) doses were found to range from about 3.5kWh/m2 (130 kWh/m2) in coastal areas to 5kWh/m2 (160kWh/m2) on the Andean plateau. Our results confirm significant interhemispherical differences. Typical annual UV-B doses in the Atacama Desert are about 40% greater than typical annual UV-B doses in northern Africa. Mostly due to seasonal changes in the ozone, the differences between the Atacama Desert and northern Africa are expected to be about 60% in the case of peak UV-B levels (i.e. the UV-B irradiances at noon close to the summer solstice in each hemisphere). Interhemispherical differences in the UV-A are significantly lower since the effect of the ozone in this part of the spectrum is minor.

Image guidance doses delivered during radiotherapy: Quantification, management, and reduction: Report of the AAPM Therapy Physics Committee Task Group 180

With radiotherapy having entered the era of image guidance, or image-guided radiation therapy (IGRT), imaging procedures are routinely performed for patient positioning and target localization. The imaging dose delivered may result in excessive dose to sensitive organs and potentially increase the chance of secondary cancers and, therefore, needs to be managed. This task group was charged with: a) providing an overview on imaging dose, including megavoltage electronic portal imaging (MV EPI), kilovoltage digital radiography (kV DR), Tomotherapy MV-CT, megavoltage cone-beam CT (MV-CBCT) and kilovoltage cone-beam CT (kV-CBCT), and b) providing general guidelines for commissioning dose calculation methods and managing imaging dose to patients. We briefly review the dose to radiotherapy (RT) patients resulting from different image guidance procedures and list typical organ doses resulting from MV and kV image acquisition procedures. We provide recommendations for managing the imaging dose, including different methods for its calculation, and techniques for reducing it. The recommended threshold beyond which imaging dose should be considered in the treatment planning process is 5% of the therapeutic target dose. Although the imaging dose resulting from current kV acquisition procedures is generally below this threshold, the ALARA principle should always be applied in practice. Medical physicists should make radiation oncologists aware of the imaging doses delivered to patients under their care. Balancing ALARA with the requirement for effective target localization requires that imaging dose be managed based on the consideration of weighing risks and benefits to the patient.

Normal tissue doses from MV image-guided radiation therapy (IGRT) using orthogonal MV and MV-CBCT.

PurposeThe aim of this study was to measure and compare the mega‐voltage imaging dose from the Halcyon medical linear accelerator (Varian Medical Systems) with measured imaging doses with the dose calculated by Eclipse treatment planning system.MethodsAn anthropomorphic thorax phantom was imaged using all imaging techniques available with the Halcyon linac — MV cone‐beam computed tomography (MV‐CBCT) and orthogonal anterior‐posterior/lateral pairs (MV‐MV), both with high‐quality and low‐dose modes. In total, 54 imaging technique, isocenter position, and field size combinations were evaluated. The imaging doses delivered to 11 points in the phantom (in‐target and extra‐target) were measured using an ion chamber, and compared with the imaging doses calculated using Eclipse.ResultsFor high‐quality MV‐MV mode, the mean extra‐target doses delivered to the heart, left lung, right lung and spine were 1.18, 1.64, 0.80, and 1.11 cGy per fraction, respectively. The corresponding mean in‐target doses were 3.36, 3.72, 2.61, and 2.69 cGy per fraction, respectively. For MV‐MV technique, the extra‐target imaging dose had greater variation and dependency on imaging field size than did the in‐target dose. Compared to MV‐MV technique, the imaging dose from MV‐CBCT was less sensitive to the location of the organ relative to the treatment field. For high‐quality MV‐CBCT mode, the mean imaging doses to the heart, left lung, right lung, and spine were 8.45, 7.16, 7.19, and 6.51 cGy per fraction, respectively. For both MV‐MV and MV‐CBCT techniques, the low‐dose mode resulted in an imaging dose about half of that in high‐quality mode.ConclusionThe in‐target doses due to MV imaging using the Halcyon ranged from 0.59 to 9.75 cGy, depending on the choice of imaging technique. Extra‐target doses from MV‐MV technique ranged from 0 to 2.54 cGy. The MV imaging dose was accurately calculated by Eclipse, with maximum differences less than 0.5% of a typical treatment dose (assuming a 60 Gy prescription). Therefore, the cumulative imaging and treatment plan dose distribution can be expected to accurately reflect the actual dose.

Spatially fractionated (GRID) radiation therapy using proton pencil beam scanning (PBS): Feasibility study and clinical implementation.

GRID therapy is an effective treatment for bulky tumors. Linear accelerator (Linac)-produced photon beams collimated through blocks or multileaf collimators (MLCs) are the most common methods used to deliver this therapy. Utilizing the newest proton delivery method of pencil beam scanning (PBS) can further improve the efficacy of GRID therapy. In this study, we developed a method of delivering GRID therapy using proton PBS, evaluated the dosimetry of this novel technique and applied this method in two clinical cases. In the feasibility study phase, a single PBS proton beam was optimized to heterogeneously irradiate a shallow 20×20×12cm3 target volume centered at a 6cm depth in a water phantom. The beam was constrained to have an identical spot pattern in all layers, creating a "beamlet" at each spot position. Another GRID treatment using PBS was also performed on a deep 15×15×8cm3 target volume centered at a 14cm depth in a water phantom. Dosimetric parameters of both PBS dose distributions were compared with typical photon GRID dose distributions. In the next phase, four patients have been treated at our center with this proton GRID technique. The planning, dosimetry, and measurements for two representative patients are reported. For the shallow phantom target, the depth-dose curve of the PBS plan was uniform within the target (variation <5%) and dropped quickly beyond the target (50% at 12.9cm and 0.5% at 14cm). The lateral profiles of the PBS plan were comparable to those of photon GRID in terms of valley-to-peak ratios. For the deep phantom target, the PBS plan provided smaller valley-to-peak ratios than the photon GRID technique. Pretreatment dose verification QA showed close agreement between the measurements and the plan (pass rate >95% with a gamma index criterion of 3%/3mm). Patients tolerated the treatment well without significant skin toxicity (radiation dermatitis grade ≤1). Proton GRID therapy using a PBS delivery method was successfully developed and implemented clinically. Proton GRID therapy offers many advantages over photon GRID techniques. The use of protons provides a more uniform beamlet dose within the tumor and spares normal tissues located beyond the tumor. This new PBS method will also reduce the dose to proximal organs when treating a deep-seated tumor.

No individual or combined effects of caffeine and beetroot-juice supplementation during submaximal or maximal running.

Dietary supplements such as caffeine and beetroot juice are used by athletes in an attempt to optimize performance and therefore gain an advantage in competition. The aim of this study was to investigate the individual and combined effects of caffeine and beetroot-juice supplementation during submaximal and maximal treadmill running. Seven males (maximal oxygen uptake: 59.0 ± 2.9 mL·kg-1·min-1) and 2 females (maximal oxygen uptake: 53.1 ± 11.4 mL·kg-1·min-1) performed a preliminary trial followed by 4 experimental test sessions. Each test session consisted of two 5-min submaximal running bouts (at ∼70% and 80% of maximal oxygen uptake) and a maximal 1-km time trial (TT) in a laboratory. Participants ingested 70 mL of concentrated beetroot juice containing either 7.3 mmol of nitrate (BR) or no nitrate (PBR) 2.5 h prior to each test session, then either caffeine (C) at 4.8 ± 0.4 (4.3-5.6) mg/kg of body mass or a caffeine placebo (PC) 45 min before each test session. The 4 test sessions (BR-C, BR-PC, PBR-C, and PBR-PC) were presented in a counterbalanced and double-blind manner. No significant differences were identified between the 4 interventions regarding relative oxygen uptake, running economy, respiratory exchange ratio, heart rate (HR), or rating of perceived exertion (RPE) at the 2 submaximal intensities (P > 0.05). Moreover, there were no significant differences in performance, maximum HR, peak blood lactate concentration, or RPE during the maximal TT when comparing the interventions (P > 0.05). In conclusion, no beneficial effects of supplementing with typical doses of caffeine, beetroot juice, or a combination of the two were observed for physiological, perceptual, or performance responses during submaximal or maximal treadmill running exercise.

1H NMR-based metabolomics reveals interactive effects between the carrier solvent methanol and a pharmaceutical mixture in an amphibian developmental bioassay with Limnodynastes peronii

Organic carrier solvents are used in aquatic toxicity testing to improve chemical solubility and facilitate the exploration of dose-response relationships. Both water- and solvent-control groups are normally included in these scenarios to ensure that the solvent itself has no effect on the test organism, but this fails to consider possible interactive effects between carrier solvents and contaminants of interest. We explored this topic by exposing Limnodynastes peronii tadpoles to a mixture of common water-soluble pharmaceuticals (diclofenac, metformin and valproic acid) in the presence and absence of the carrier solvent methanol, according to standard developmental bioassay methodology. Nuclear Magnetic Resonance (NMR) spectroscopy was applied as a platform for untargeted metabolomics, to compare broad sub-lethal hepatotoxicity in solvent- and solvent-free exposure scenarios. Considerable interactive effects were identified between the pharmaceutical mixture and a typical dose of methanol (0.003%). Specifically, pronounced differences were observed between the solvent- and solvent-free exposure groups for leucine, acetate, glutamine, citrate, glycogen, tyrosine, arginine, purine nucleotides and an unidentified metabolite at 6.53 ppm. Various other metabolites exhibited similar disparity related to the use of carrier solvent, but the interactions were non-significant. These results raise important questions about the use of carrier solvents for chemical exposures in aquatic ecotoxicology, and particularly for studies interested in sub-lethal mechanistic information and/or biomarker discovery.

Typical doses and dose rates in studies pertinent to radiation risk inference at low doses and low dose rates.

In order to quantify radiation risks at exposure scenarios relevant for radiation protection, often extrapolation of data obtained at high doses and high dose rates down to low doses and low dose rates is needed. Task Group TG91 on ‘Radiation Risk Inference at Low-dose and Low-dose Rate Exposure for Radiological Protection Purposes’ of the International Commission on Radiological Protection is currently reviewing the relevant cellular, animal and human studies that could be used for that purpose. This paper provides an overview of dose rates and doses typically used or present in those studies, and compares them with doses and dose rates typical of those received by the A-bomb survivors in Japan.

Ozonation of municipal wastewater effluent containing metal sulfides and metal complexes: Kinetics and mechanisms

Ozonation can be applied to mitigate the discharge of organic micropollutants from municipal wastewater treatment plants (WWTPs) to the aquatic environment. The toxicity of metals also present in WWTP effluents strongly depends on their speciation. Therefore, knowledge on the change of the metal speciation during ozonation of a WWTP effluent is essential to assess possible negative impacts. The kinetics and the stoichiometries of the reactions of ozone with three metal sulfides (ZnS, CuS and CdS) and metal-ethylenediaminetetraacetate (EDTA)/nitriloriacetic acid (NTA) complexes of Cu(II), Cd(II), Ni(II), Zn(II), Mg(II) and Pb(II) were investigated. With a stoichiometric factor of 2.6–3.9 moles of ozone per mole of sulfide and apparent second-order rate constants at pH 8 > 104 M−1 s−1, a complete oxidation of the sulfides and a concomitant release of the respective metals is expected during ozonation of a WWTP effluent for enhanced micropollutant abatement. The apparent second-order rate constants at pH 8 for the reactions of metal-EDTA complexes with ozone ranged from 42 M−1s−1 to 2.0 × 104 M−1s−1 and increased in the order Cd(II) < Cu(II) < Mg(II) < Ni(II) < Zn(II). Approximately 40% of Cd(II)-EDTA spiked to a WWTP effluent was oxidized at typical specific ozone doses of 0.5–0.7 gO3/gDOC. For the other metal-EDTA complexes a significantly higher fraction was oxidized. The bioavailable fraction determined by the diffusive-gradient thin films (DGT) method in the WWTP effluent increased during ozonation, due to the oxidative release of the metal ions. Algal toxicity (chlamynomodas reinhardtii) tests with CuS/CdS spiked WWTP effluent revealed a high tolerance toward Cu and Cd in the respective media. A toxic response was only observed at Cu concentrations above 10 μM, which is above typical WWTP effluent concentrations. Biological post-treatment after ozonation generally reduced the bioavailability of the metals, which resulted in a lower toxicity. Therefore, the biological post-treatment serves as an additional barrier to protect the downstream ecology of receiving waters.

Theoretical and experimental comparison of proton and helium-beam radiography using silicon pixel detectors

Ion-beam radiography (iRad) could potentially improve the quality control of ion-beam therapy. The main advantage of iRad is the possibility to directly measure the integrated stopping power. Until now there is no clinical implementation of iRad. Topics of ongoing research include developing dedicated detection systems to achieve the desired spatial resolution (SR) and investigating different ion types as imaging radiation. This work focuses on the theoretical and experimental comparison of proton (pRad) and helium-beam radiography (αRad).The experimental comparison was performed with an in-house developed detection system consisting of silicon pixel detectors. This system enables the measurement of energy deposition of single ions, their tracking, and the identification of the ion type, which is important for αRad due to secondary fragments. A 161 mm-thick PMMA phantom with an air gap of 1 mm placed at different depths was imaged with a 168 MeV u−1 proton/helium-ion beam at the Heidelberg ion-beam therapy center. The image quality in terms of SR and contrast-to-noise ratio (CNR) was evaluated. After validating MC simulations against experiments, pRad and αRad were compared to carbon-beam radiography (cRad) in simulations.The theoretical prediction that the CNR of pRad and αRad is equal at similar imaging doses was experimentally confirmed. The measured SR of αRad was 55% better compared to pRad. The simulated cRads showed the expected improvement in SR and the decreased CNR at the same dose compared to the αRads, however only at dose levels exceeding typical doses of diagnostic x-ray projections. For clinically applicable dose levels, the cRads suffered from an insufficient number of carbon ions per pixel (220 μm × 220 μm).In conclusion, it was theoretically and experimentally shown that αRad provides a better SR than pRad without any disadvantages concerning the CNR. Using carbon ions instead of helium ions leads to a better SR at the cost of higher doses.