The Evidence for Excess Risk of Cancer and Non-Cancer Disease at Low Doses and Dose Rates.

The question of whether there are excess radiation-associated health risks at low dose is controversial. We present evidence of excess cancer risks in a number of (largely pediatrically or in utero exposed) groups exposed to low doses of radiation (<0.1 Gy). Moreover, the available data on biological mechanisms do not provide support for the idea of a low-dose threshold or hormesis for any of these endpoints. There are emerging data suggesting risks of cardiovascular disease and cataract at low doses, but this is less well established. This large body of evidence does not suggest and, indeed, is not statistically compatible with any very large threshold in dose (>10 mGy), or with possible beneficial effects from exposures. The presented data suggest that exposure to low-dose radiation causes excess cancer risks and quite possibly also excess risks of various non-cancer endpoints.

Care for Adolescents With Polycystic Ovary Syndrome: Development and Prescribing Patterns of a Multidisciplinary Clinic.

STUDY OBJECTIVE: Based on updated guidelines and expressed patient needs, we created a multidisciplinary clinic including endocrinology, gynecology/adolescent medicine, dermatology, psychology, and nutrition to provide comprehensive care to adolescent girls with polycystic ovary syndrome (PCOS). We describe the patient population presenting to this clinic, and prescribing patterns when a multidisciplinary approach is used. DESIGN: Retrospective chart review. SETTING: Tertiary care hospital. PARTICIPANTS: Female patients, aged 11-24 years, presenting for initial assessment in a multidisciplinary PCOS clinic. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Medical history, physical examination findings, laboratory measurements and prescribed therapies. RESULTS: A total of 92 patients seen from 2014 to 2018 are described (age 15.9 years, range 11-24 years, body mass index 35.6 kg/m2, range 19.9-53.5). Metabolic syndrome features were common: 26% had a prediabetes hemoglobin A1c (>5.6%), 83% had a high-density lipoprotein (HDL) <50 mg/dL, 40% had a systolic blood pressure >120 mm Hg, and 43% had an alanine aminotransferase level of >30 U/L. Dermatologic findings included acne 93%, hirsutism 38%, acanthosis nigricans 85%, hidradenitis suppurativa 16%, and androgenic alopecia 2%. Of the patients, 33% had a diagnosis of depression or anxiety, 16% of patients had a diagnosis of obstructive sleep apnea, and an additional 59% had symptoms warranting a sleep study The most commonly prescribed medications were topical acne preparations (62%), followed by estrogen-containing hormonal therapy (56%) and metformin (40%). CONCLUSION: In adolescents with PCOS and obesity, metabolic, dermatologic, and psychologic co-morbidities are common. The use of a multidisciplinary clinic model including dermatology in addition to endocrinology, gynecology, psychology, and lifestyle experts provides care for most aspects of PCOS.

Trends in Estimated Thyroid, Salivary Gland, Brain, and Eye Lens Doses From Intraoral Dental Radiography Over Seven Decades (1940 TO 2009).

The purpose of this study is to support retrospective dose estimation for epidemiological studies by providing estimates of historical absorbed organ doses to the brain, lens of the eye, salivary glands, and thyroid from intraoral dental radiographic examinations performed from 1940 to 2009. We simulated organ doses to an adult over 10 y time periods from 1940 to 2009, based on commonly used sets of x-ray machine settings collected from the literature. Simulations to estimate organ dose were performed using personal computer x-ray Monte Carlo software. Overall, organ doses were less than 1 mGy for a single intraoral radiograph for all decades. From 1940 to 2009, doses to the brain, eye lens, salivary glands, and thyroid decreased by 86, 96, 95, and 89%, respectively. Of these four organs, the salivary glands received the highest doses, with values decreasing from about 0.23 mGy in the 1940s to 0.025 mGy in the 2000s for a single intraoral radiograph. Based on simulations using collected historical data on x-ray technical parameters, improvements in technology and optimization of the technical settings used to perform intraoral dental radiography have resulted in a decrease in absorbed dose to the brain, eye lens, salivary glands, and thyroid over the period from 1940 to 2009.

The State Scientific Automated Medical Registry, Kazakhstan: an important resource for low-dose radiation health research.

Direct quantitative assessment of health risks following exposure to ionizing radiation is based on findings from epidemiological studies. Populations affected by nuclear bomb testing are among those that allow such assessment. The population living around the former Soviet Union's Semipalatinsk nuclear test site is one of the largest human cohorts exposed to radiation from nuclear weapons tests. Following research that started in the 1960s, a registry that contains information on more than 300,000 individuals residing in the areas neighboring to the test site was established. Four nuclear weapons tests, conducted from 1949 to 1956, resulted in non-negligible radiation exposures to the public, corresponding up to approximately 300 mGy external dose. The registry contains relevant information about those who lived at the time of the testing as well as about their offspring, including biological material. An international group of scientists worked together within the research project SEMI-NUC funded by the European Union, and concluded that the registry provides a novel, mostly unexplored, and valuable resource for the assessment of the population risks associated with environmental radiation exposure. Suggestions for future studies and pathways on how to use the best dose assessment strategies have also been described in the project. Moreover, the registry could be used for research on other relevant public health topics.

Breast cancer risk and protracted low-to-moderate dose occupational radiation exposure in the US Radiologic Technologists Cohort, 1983-2008.

BACKGROUND: Although high-dose ionising radiation is associated with increased breast cancer risks, the association with protracted low-dose-rate exposures remains unclear. The US Radiologic Technologist study provides an opportunity to examine the association between low-to-moderate dose radiation and breast cancer incidence and mortality. METHODS: One thousand nine hundred and twenty-two self-reported first primary cancers were diagnosed during 1983-2005 among 66 915 female technologists, and 586 breast cancer deaths occurred during 1983-2008 among 83 538 female cohort members. Occupational breast dose estimates were based on work histories, historical data, and, after the mid-1970s, individual film badge measurements. Excess relative risks were estimated using Poisson regression with birth cohort stratification and adjustment for menopause, reproductive history, and other risk factors. RESULTS: Higher doses were associated with increased breast cancer incidence, with an excess relative risk at 100 mGy of 0.07 (95% confidence interval (CI): -0.005 to 0.19). Associations were strongest for technologists born before 1930 (excess relative risk at 100 mGy=0.16; 95% CI: 0.03-0.39) with similar patterns for mortality among technologists born before 1930. CONCLUSIONS: Occupational radiation to the breast was positively associated with breast cancer risk. The risk was more pronounced for women born before 1930 who began working before 1950 when mean annual doses (37 mGy) were considerably higher than in later years (1.3 mGy). However, because of the uncertainties and possible systematic errors in the occupational dose estimates before 1960, these findings should be treated with caution.

Emergency Dose Estimation Using Optically Stimulated Luminescence from Human Tooth Enamel.

Human teeth were studied for potential use as emergency Optically Stimulated Luminescence (OSL) dosimeters. By using multiple-teeth samples in combination with a custom-built sensitive OSL reader, (60)Co-equivalent doses below 0.64 Gy were measured immediately after exposure with the lowest value being 27 mGy for the most sensitive sample. The variability of OSL sensitivity, from individual to individual using multiple-teeth samples, was determined to be 53%. X-ray and beta exposure were found to produce OSL curves with the same shape that differed from those due to ultraviolet (UV) exposure; as a result, correlation was observed between OSL signals after X-ray and beta exposure and was absent if compared to OSL signals after UV exposure. Fading of the OSL signal was "typical" for most teeth with just a few of incisors showing atypical behavior. Typical fading dependences were described by a bi-exponential decay function with "fast" (decay time around of 12 min) and "slow" (decay time about 14 h) components. OSL detection limits, based on the techniques developed to-date, were found to be satisfactory from the point-of-view of medical triage requirements if conducted within 24 hours of the exposure.

UV effects in tooth enamel and their possible application in EPR dosimetry with front teeth.

The effects of ultraviolet (UV) radiation on ionizing radiation biodosimetry were studied in human tooth enamel samples using the technique of electron paramagnetic resonance (EPR) in X-band. For samples in the form of grains, UV-specific EPR spectra were spectrally distinct from those produced by exposure to gamma radiation. From larger enamel samples, the UV penetration depth was determined to be in the 60-120 mum range. The difference in EPR spectra from UV exposure and from exposure to gamma radiation samples was found to be a useful marker of UV equivalent dose (defined as the apparent contribution to the gamma dose in mGy that results from UV radiation absorption) in tooth enamel. This concept was preliminarily tested on front teeth from inhabitants of the region of the Semipalatinsk Nuclear Test Site (Kazakhstan) who might have received some exposure to gamma radiation from the nuclear tests conducted there as well as from normal UV radiation in sunlight. The technique developed here to quantify and subtract the UV contribution to the measured tooth is currently limited to cumulative dose measurements with a component of UV equivalent dose equal to or greater than 300 mGy.

Optically stimulated luminescence (OSL) of tooth enamel and its potential use in post-radiation exposure triage.

Optically stimulated luminescence (OSL) properties of dental enamel are discussed with a view to the development of an in vivo dose assessment technique for medical triage following a radiological/nuclear accident or terrorist event. In the OSL technique, past radiation exposure is assessed by stimulating the sample with light of one wavelength and monitoring the luminescence at another wavelength, under the assumption that the luminescence originates from the recombination of radiation-induced charges trapped at metastable defects in the enamel and that the intensity of the luminescence signal is in proportion to the absorbed radiation dose. Several primary findings emerged from this research: (a) sensitivities varied considerably between different teeth and also between fragments of the same tooth, (b) OSL signals were found to decay rapidly during the first 12 h after irradiation and more slowly afterward, (c) the fading rate of the luminescence signal varied between fragments, and (d) blue light stimulation yields greater sensitivity than infra-red stimulation, while the OSL signal obtained with a high-intensity pulsed green-light laser was found not to be correlated with the radiation dose. Significant challenges remain to developing a practical in vivo technique, including the development of calibration procedures and lowering minimum detectable doses.

Validation of 131I ecological transfer models and thyroid dose assessments using Chernobyl fallout data from the Plavsk district, Russia.

Within the project "Environmental Modelling for Radiation Safety" (EMRAS) organized by the IAEA in 2003 experimental data of (131)I measurements following the Chernobyl accident in the Plavsk district of Tula region, Russia were used to validate the calculations of some radioecological transfer models. Nine models participated in the inter-comparison. Levels of (137)Cs soil contamination in all the settlements and (131)I/(137)Cs isotopic ratios in the depositions in some locations were used as the main input information. 370 measurements of (131)I content in thyroid of townspeople and villagers, and 90 measurements of (131)I concentration in milk were used for validation of the model predictions. A remarkable improvement in models performance comparing with previous inter-comparison exercise was demonstrated. Predictions of the various models were within a factor of three relative to the observations, discrepancies between the estimates of average doses to thyroid produced by most participant not exceeded a factor of ten.

Radiation dose to the brain and subsequent risk of developing brain tumors in pediatric patients undergoing interventional neuroradiology procedures.

Radiation dose to the brain and subsequent lifetime risk of diagnosis of radiation-related brain tumors were estimated for pediatric patients undergoing intracranial embolization. Average dose to the whole brain was calculated using dosimetric data from the Radiation Doses in Interventional Radiology Study for 49 pediatric patients who underwent neuroradiological procedures, and lifetime risk of developing radiation-related brain tumors was estimated using published algorithms based on A-bomb survivor data. The distribution of absorbed dose within the brain can vary significantly depending on field size and movement during procedures. Depending on the exposure conditions and age of the patient, organ-averaged brain dose was estimated to vary from 6 to 1600 mGy. The lifetime risk of brain tumor diagnosis was estimated to be increased over the normal background rates (57 cases per 10,000) by 3 to 40% depending on the dose received, age at exposure, and gender. While significant uncertainties are associated with these estimates, we have quantified the range of possible dose and propagated the uncertainty to derive a credible range of estimated lifetime risk for each subject. Collimation and limiting fluoroscopy time and dose rate are the most effective means to minimize dose and risk of future induction of radiation-related tumors.

Childhood cancer in the offspring born in 1921-1984 to US radiologic technologists.

We examined the risk of childhood cancer (<20 years) among 105 950 offspring born in 1921-1984 to US radiologic technologist (USRT) cohort members. Parental occupational in utero and preconception ionising radiation (IR) testis or ovary doses were estimated from work history data, badge dose data, and literature doses (the latter doses before 1960). Female and male RTs reported a total of 111 and 34 haematopoietic malignancies and 115 and 34 solid tumours, respectively, in their offspring. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. Leukaemia (n=63) and solid tumours (n=115) in offspring were not associated with maternal in utero or preconception radiation exposure. Risks for lymphoma (n=44) in those with estimated doses of <0.2, 0.2-1.0, and >1.0 mGy vs no exposure were non-significantly elevated with HRs of 2.3, 1.8, and 2.7. Paternal preconception exposure to estimated cumulative doses above the 95th percentile (82 mGy, n=6 cases) was associated with a non-significant risk of childhood cancer of 1.8 (95% CI 0.7-4.6). In conclusion, we found no convincing evidence of an increased risk of childhood cancer in the offspring of RTs in association with parental occupational radiation exposure.

Ultrasound-detected thyroid nodule prevalence and radiation dose from fallout.

Settlements near the Semipalatinsk Test Site (SNTS) in northeastern Kazakhstan were exposed to radioactive fallout during 1949-1962. Thyroid disease prevalence among 2994 residents of eight villages was ascertained by ultrasound screening. Malignancy was determined by cytopathology. Individual thyroid doses from external and internal radiation sources were reconstructed from fallout deposition patterns, residential histories and diet, including childhood milk consumption. Point estimates of individual external and internal dose averaged 0.04 Gy (range 0-0.65) and 0.31 Gy (0-9.6), respectively, with a Pearson correlation coefficient of 0.46. Ultrasound-detected thyroid nodule prevalence was 18% and 39% among males and females, respectively. It was significantly and independently associated with both external and internal dose, the main study finding. The estimated relative biological effectiveness of internal compared to external radiation dose was 0.33, with 95% confidence bounds of 0.09-3.11. Prevalence of papillary cancer was 0.9% and was not significantly associated with radiation dose. In terms of excess relative risk per unit dose, our dose-response findings for nodule prevalence are comparable to those from populations exposed to medical X rays and to acute radiation from the Hiroshima and Nagasaki atomic bombings.

Optically Stimulated Luminescence (OSL) of dental enamel for retrospective assessment of radiation exposure.

This paper briefly reviews the optically stimulated luminescence (OSL) properties of dental enamel and discusses the potential and challenges of OSL for filling the technology gap in biodosimetry required for medical triage following a radiological/nuclear accident or terrorist event. The OSL technique uses light to stimulate a radiation-induced luminescence signal from materials previously exposed to ionizing radiation. This luminescence originates from radiation-induced defects in insulating crystals and is proportional to the absorbed dose of ionizing radiation. In our research conducted to date, we focused on fundamental investigations of the OSL properties of dental enamel using extracted teeth and tabletop OSL readers. The objective was to obtain information to support the development of the necessary instrumentation for retrospective dosimetry using dental enamel in laboratory, or for in situ and non-invasive accident dosimetry using dental enamel in emergency triage. An OSL signal from human dental enamel was detected using blue, green, or IR stimulation. Blue/green stimulation associated with UV emission detection seems to be the most appropriate combination in the sense that there is no signal from un-irradiated samples and the shape of the OSL decay is clear. Improvements in the minimum detection level were achieved by incorporating an ellipsoidal mirror in the OSL system to maximize light collection. Other possibilities to improve the sensitivity and research steps necessary to establish the feasibility of the technique for retrospective assessment of radiation exposure are also discussed.

Uptake of 40K and 137Cs in native plants of the Marshall Islands.

Uptake of 137Cs and 40K was studied in seven native plant species of the Marshall Islands. Plant and soil samples were obtained across a broad range of soil 137Cs concentrations (0.08-3900 Bq/kg) and a narrower range of 40K soil concentrations (2.3-55 Bq/kg), but with no systematic variation of 40K relative to 137Cs. Potassium-40 concentrations in plants varied little within the range of 40K soil concentrations observed. Unlike the case for 40K, 137Cs concentrations increased in plants with increasing 137Cs soil concentrations though not precisely in a proportionate manner. The best-fit relationship between soil and plant concentrations was P = aSb where a and b are regression coefficients and P and S are plant and soil concentrations, respectively. The exponent b for 40K was zero, implying plant concentrations were a single value, while b for 137Cs varied between 0.51 and 0.82, depending on the species. For both 40K and 137Cs, we observed a decreasing concentration ratio (where concentration ratio=plant concentration/soil concentration) with increasing soil concentrations. For the CR values, the best-fit relationship was of the form CR = aSb/S = aSb(-1). For the 40K CR functions, the exponent b - 1 was close to - 1 for all species. For the 137Cs CR functions, the exponent b - 1 varied from -0.19 to -0.48. The findings presented here, aswell as those by other investigators, collectively argue against the usefulness of simplistic ratio models to accurately predict uptake of either 40K or 137Cs in plants over wide ranges of soil concentration.

Effects of entanglement concentration on Tg and local segmental motions.

The process of spin-coating to fabricate thin polymer films with high molecular weight can produce samples with entanglement concentrations that are far below the equilibrium value. It is not clear whether or not such low entanglement concentrations are responsible for the depression of the glass temperature in thin polymer films. In this work, we measure the calorimetric glass temperature and viscoelastic response of polystyrenes with molecular weights ranging from 3x10(3) to 43.7x10(6) g/mol, for both bulk material and for samples freeze-dried from dilute solution. We conclude that the reduction of the glass temperature observed in thin polymer films cannot be due to the reduced entanglement concentration in the samples.

Enthalpy recovery of a glass-forming liquid constrained in a nanoporous matrix: negative pressure effects.

The T(g) of organic liquids confined to nanoporous matrices and that of thin polymer films can decrease dramatically from the bulk value. One possible explanation for this phenomenon is the development of hydrostatic tension during vitrification under confinement that results in a concomitant increase in the free volume. Here we present experimental evidence and modeling results for ortho-terphenyl (o-TP) confined in pores as small as 11.6 nm that indicate that, although there is an important hydrostatic tension in the liquid in the pores, it does not develop until near the reduced T(g) of the constrained material --well below the bulk T(g). Enthalpy recovery for the o-TP in the nanopores exhibits accelerated physical aging relative to the bulk, as well as a leveling off of the fictive temperature at equilibrium values greater than the aging temperature. An adaptation of the structural recovery model that incorporates vitrification under isochoric conditions is able to provide a quantitative explanation for the apparently anomalous aging observed in nanopore confined liquids and in thin polymeric films. The results strongly support the existence of an intrinsic size effect as the cause of the reduced T(g).

Altered expression of estrogen receptor coregulators during human breast tumorigenesis.

The hypothesis that altered expression of specific coactivators/repressors of the estrogen receptor occurs during human breast tumorigenesis in vivo is examined in this study. Using in situ hybridization and reverse transcription-PCR assays, the expression of two coactivators (SRA and AIB1) and one repressor (REA) of the estrogen receptor was compared between matched breast tumors and adjacent normal human breast tissue. The levels of SRA and AIB1 mRNA were increased in tumors compared with normal tissues (n = 19; Wilcoxon matched pairs test; P < 0.01). In contrast, the expression of REA mRNA was not different between tumors and normal tissues (n = 19; Wilcoxon; P = 0.110). The ratios of AIB1:REA and SRA:REA were higher (Wilcoxon; P < 0.05) in tumors compared with normal tissues. Furthermore, SRA:AIB1 was higher (Wilcoxon; P = 0.0058) in tumors compared with normal tissues. Although our study is small, these data are consistent with the above hypothesis and suggest that such alterations may have a role in the altered estrogen action occurring during breast tumorigenesis.

Cognitive impairment in individuals currently using methamphetamine.

Although there are increasing reports of methamphetamine use, studies examining the cognitive consequences of methamphetamine have not been performed on a population currently using the drug. To characterize this population, 65 people currently using MA regularly and 65 non-users were given a battery of cognitive tests. The battery included recall, recognition, Digit Symbol, Trail Making A & B, Stroop, Wisconsin Card Sort, backward digit span, and the FAS test of verbal fluency. The methamphetamine users were significantly more impaired on recall tasks, digit symbol, Stroop color words, and Trail Making B, but scores fell within the normal ranges on the other measures.

A comparison of injecting and noninjecting methamphetamine users.

The injection of illicit drugs exposes the user to a variety of risks that are not associated with other routes of administration. Information regarding differences between injecting and noninjecting methamphetamine (MA) users is provided. The population studied included MA dependent men and women (n = 427) from the Matrix Institute on Addictions in San Bernardino County, California. The sample was divided into two groups according to their injecting status; 55 individuals (13%) reported injecting, and 372 (87%) reported no history of injecting MA. Differences were found in specific use patterns and in medical, criminal, and psychological histories between the two groups.