scholarly journals Issues in Interpreting Epidemiologic Studies of Populations Exposed to Low-Dose, High-Energy Photon Radiation

2020 ◽  
Vol 2020 (56) ◽  
pp. 176-187 ◽  
Author(s):  
Ethel S Gilbert ◽  
Mark P Little ◽  
Dale L Preston ◽  
Daniel O Stram
Keyword(s):  
Measurement Errors ◽  
Statistical Power ◽  
Low Dose ◽  
Risk Model ◽  
Atomic Bomb ◽  
Statistical Tests ◽  
High Energy ◽  
Epidemiologic Studies ◽  
Photon Radiation ◽  
High Dose

Abstract This article addresses issues relevant to interpreting findings from 26 epidemiologic studies of persons exposed to low-dose radiation. We review the extensive data from both epidemiologic studies of persons exposed at moderate or high doses and from radiobiology that together have firmly established radiation as carcinogenic. We then discuss the use of the linear relative risk model that has been used to describe data from both low- and moderate- or high-dose studies. We consider the effects of dose measurement errors; these can reduce statistical power and lead to underestimation of risks but are very unlikely to bring about a spurious dose response. We estimate statistical power for the low-dose studies under the assumption that true risks of radiation-related cancers are those expected from studies of Japanese atomic bomb survivors. Finally, we discuss the interpretation of confidence intervals and statistical tests and the applicability of the Bradford Hill principles for a causal relationship.

scholarly journals Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects

2012 ◽  
Vol 108 (9) ◽  
pp. 1652-1657 ◽  
Author(s):  
Elke Theuwissen ◽  
Ellen C. Cranenburg ◽  
Marjo H. Knapen ◽  
Elke J. Magdeleyns ◽  
Kirsten J. Teunissen ◽  
...  
Keyword(s):  
Vitamin K ◽  
Statistical Power ◽  
Thrombin Generation ◽  
Low Dose ◽  
Coagulation Factors ◽  
Peak Height ◽  
Matrix Gla Protein ◽  
High Dose ◽  
Age Related ◽  
Intervention Trials

Vitamin K is required for the carboxylation of Gla-proteins in the liver (coagulation factors) and extra-hepatic tissues, such as bone (osteocalcin, OC), and arterial wall (matrix Gla-protein, MGP). Although the coagulation factors are essentially fully carboxylated under normal conditions, 10–40 % of OC and MGP remains undercarboxylated. We were therefore interested to study the dose–response effects of extra intake of menaquinones on the carboxylation of the extra-hepatic Gla-proteins. A total of forty-two healthy Dutch men and women aged between 18 and 45 years were randomised into seven groups to receive: placebo capsules or menaquinone-7 (MK-7) capsules at a daily dose of 10, 20, 45, 90, 180 or 360 μg. Circulating uncarboxylated OC (ucOC), carboxylated OC (cOC) and desphospho-uncarboxylated MGP were measured by ELISA. The ucOC:cOC ratio was calculated from circulating ucOC and cOC values. Endogenous thrombin potential and peak height were determined by calibrated automated thrombography. To increase the statistical power, we collapsed the treatment groups into three dosage groups: placebo, low-dose supplementation (doses below RDA, Commission Directive 2008/100/EC), and high-dose supplementation (doses around RDA, Commission Directive 2008/100/EC). MK-7 supplementation at doses in the order of the RDA (Commission Directive 2008/100/EC) increased the carboxylation of circulating OC and MGP. No adverse effects on thrombin generation were observed. Extra MK-7 intake at nutritional doses around the RDA (Commission Directive 2008/100/EC) improved the carboxylation of the extra-hepatic vitamin K-dependent proteins. Whether this improvement contributes to public health, i.e. increasing the protection against age-related diseases needs further investigation in specifically designed intervention trials.

scholarly journals Carcinogenesis induced by low-dose radiation

2017 ◽  
Vol 51 (4) ◽  
pp. 369-377 ◽  
Author(s):  
Igor Piotrowski ◽  
Katarzyna Kulcenty ◽  
Wiktoria Maria Suchorska ◽  
Agnieszka Skrobała ◽  
Małgorzata Skórska ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Low Dose ◽  
Atomic Bomb ◽  
Threshold Model ◽  
Occupational Exposures ◽  
High Dose ◽  
Low Dose Radiation ◽  
Oncologic Patients ◽  
Risk Of Cancer ◽  
Dose Radiation

AbstractBackgroundAlthough the effects of high dose radiation on human cells and tissues are relatively well defined, there is no consensus regarding the effects of low and very low radiation doses on the organism. Ionizing radiation has been shown to induce gene mutations and chromosome aberrations which are known to be involved in the process of carcinogenesis. The induction of secondary cancers is a challenging long-term side effect in oncologic patients treated with radiation. Medical sources of radiation like intensity modulated radiotherapy used in cancer treatment and computed tomography used in diagnostics, deliver very low doses of radiation to large volumes of healthy tissue, which might contribute to increased cancer rates in long surviving patients and in the general population. Research shows that because of the phenomena characteristic for low dose radiation the risk of cancer induction from exposure of healthy tissues to low dose radiation can be greater than the risk calculated from linear no-threshold model. Epidemiological data collected from radiation workers and atomic bomb survivors confirms that exposure to low dose radiation can contribute to increased cancer risk and also that the risk might correlate with the age at exposure.ConclusionsUnderstanding the molecular mechanisms of response to low dose radiation is crucial for the proper evaluation of risks and benefits that stem from these exposures and should be considered in the radiotherapy treatment planning and in determining the allowed occupational exposures.

Reduction of Secondary Defects in High Energy O-Implanted Si by High Energy Si Irradiation

1992 ◽  
Vol 279 ◽  
Author(s):  
S. L. Ellingboe ◽  
M. C. Ridgway
Keyword(s):  
High Temperature ◽  
Defect Structure ◽  
Low Dose ◽  
Defect Formation ◽  
Volume Fraction ◽  
High Energy ◽  
High Dose ◽  
High Temperature Annealing ◽  
Before And After ◽  
Secondary Defect

ABSTRACTThe effect of 4.2 MeV, low dose Si irradiation before annealing of 1 MeV, high dose O-implanted Si has been studied. Si irradiation results in differences in the defect structure both before and after high temperature annealing. With no Si irradiation, annealing results in polycrystalline Si (polySi) formation and microtwinning at the front SiO2/Si interface. With Si irradiation, the polySi volume fraction is greatly reduced after annealing, twinned Si having grown in its place. Si irradiation has no effect on Si inclusions within the SiO2 layer. The dependence of secondary defect formation on Si dose and implant temperature is presented. In particular, Si irradiation at low implant temperatures (150°C) and moderate doses (5×1016 cm−2) is shown to be most effective in the reduction of the polySi volume fraction at the front SiO2/Si interface.

scholarly journals Evaluation of Confounding and Selection Bias in Epidemiological Studies of Populations Exposed to Low-Dose, High-Energy Photon Radiation

2020 ◽  
Vol 2020 (56) ◽  
pp. 133-153 ◽  
Author(s):  
Mary K Schubauer-Berigan ◽  
Amy Berrington de Gonzalez ◽  
Elisabeth Cardis ◽  
Dominique Laurier ◽  
Jay H Lubin ◽  
...  
Keyword(s):  
Selection Bias ◽  
Low Dose ◽  
Indirect Evidence ◽  
High Energy ◽  
Photon Radiation ◽  
Main Concern ◽  
Primary Concern ◽  
Medical Studies ◽  
Survivor Bias ◽  
Cancer Studies

Abstract Background Low-dose, penetrating photon radiation exposure is ubiquitous, yet our understanding of cancer risk at low doses and dose rates derives mainly from high-dose studies. Although a large number of low-dose cancer studies have been recently published, concern exists about the potential for confounding to distort findings. The aim of this study was to describe and assess the likely impact of confounding and selection bias within the context of a systematic review. Methods We summarized confounding control methods for 26 studies published from 2006 to 2017 by exposure setting (environmental, medical, or occupational) and identified confounders of potential concern. We used information from these and related studies to assess evidence for confounding and selection bias. For factors in which direct or indirect evidence of confounding was lacking for certain studies, we used a theoretical adjustment to determine whether uncontrolled confounding was likely to have affected the results. Results For medical studies of childhood cancers, confounding by indication (CBI) was the main concern. Lifestyle-related factors were of primary concern for environmental and medical studies of adult cancers and for occupational studies. For occupational studies, other workplace exposures and healthy worker survivor bias were additionally of interest. For most of these factors, however, review of the direct and indirect evidence suggested that confounding was minimal. One study showed evidence of selection bias, and three occupational studies did not adjust for lifestyle or healthy worker survivor bias correlates. Theoretical adjustment for three factors (smoking and asbestos in occupational studies and CBI in childhood cancer studies) demonstrated that these were unlikely to explain positive study findings due to the rarity of exposure (eg, CBI) or the relatively weak association with the outcome (eg, smoking or asbestos and all cancers). Conclusion Confounding and selection bias are unlikely to explain the findings from most low-dose radiation epidemiology studies.

Epidemiologic Issues Related to Nasopharyngeal Radium Exposures

1996 ◽  
Vol 115 (5) ◽  
pp. 422-428
Author(s):  
Roy E. Shore
Keyword(s):  
Sample Size ◽  
Statistical Power ◽  
Radiation Risk ◽  
Epidemiologic Study ◽  
Epidemiologic Studies ◽  
High Dose ◽  
Large Sample Size ◽  
Organ Doses ◽  
Scientific Advance ◽  
The Impact

A number of topics are discussed related to the potential for and pitfalls in undertaking epidemiologic studies of the late effects of nasopharyngeal radium irradiation. The available evidence indicates that linear extrapolation of risk estimates from high-dose studies is a reasonable basis for estimating risk from radium exposure or other situations in which the radiation exposures were fairly low and fractionated. Epidemiologic study of populations given nasopharyngeal radium irradiation is worthwhile scientifically if several criteria can be met. It is very Important that any such study has adequate statistical power, which is a function of the doses to the organs of interest and the radiation risk coefficients for those organs, as wed as the available sample size. If the organ doses are low, a prohibitively large sample size would be required. Other problems with low-dose studies include the likelihood of false-positive results when a number of health end points are evaluated and the impact of dose uncertainties, small biases, and confounding factors that make the interpretation uncertain. Cluster studies or studies of self-selected cohorts of irradiated patients are not recommended because of the potential for severe bias with such study designs. The ability to define subgroups of the population who have heightened genetic susceptibility may become a reality in the next few years as genes conferring susceptibility to brain cancers or other head and neck tumors are identified; this scientific advance would have the potential to alter greatly the prospects and approaches of epidemiologic studies.

scholarly journals THE ROLE OF TREATMENT WITH HIGH-DOSE CORTICOSTEROIDS IN SEVERE LEPTOSPIROSIS WITH PULMONARY COMPLICATIONS

2019 ◽  
pp. 63-71
Author(s):  
MARIA SATYA PARAMITHA ◽  
SUTRISUNA ◽  
MYRA PUSPITASARI
Keyword(s):  
Systematic Review ◽  
Statistical Power ◽  
Low Dose ◽  
Pulmonary Complications ◽  
High Dose ◽  
Therapeutic Effects ◽  
Statistical Heterogeneity ◽  
Significant Difference ◽  
Severe Leptospirosis

Objective: To investigate the effectiveness of high-dose corticosteroids in patients with severe leptospirosis, especially in reducing morbidity and mortality rates. Methods: Literature searches were conducted using PubMed® and SCOPUS®. One systematic review and one systematic review with meta-analysis were selected from three chosen studies. Results: The systematic review from Rodrigo et al. only included qualitative synthesis from four interventional studies. Early administration of methylprednisolone can be beneficial; however, low number and poor methodological quality of the studies question the validity of this review. Duggal et al. stated that there was no significant difference in the therapeutic effects of early high-dose corticosteroids (P ³ 0.05; 95% CI: 0.81–1.37), early low-dose corticosteroids (P ³ 0.05; 95% CI: 0.3–1.03), and late low-dose corticosteroids (P ³ 0.05; 95% CI: 0.11–2.52). Limited number of studies and high statistical heterogeneity, however, are major drawbacks for this review. Conclusion: Evidence about the role of high-dose corticosteroids in severe leptospirosis patients with pulmonary complications, especially their benefits, is still limited. Additional randomized, controlled trials with adequate statistical power still need to be conducted.

Vergleich der biologischen Strahlenwirkung des β--Emitters 186Re mit 662 keV Photonenstrahlung auf die humane B-Zelllinie BV-173

2021 ◽  
Vol 60 (06) ◽  
pp. 438-444
Author(s):  
Jennifer Staudt ◽  
Christian Happel ◽  
Wolfgang Tilman Kranert ◽  
Benjamin Bockisch ◽  
Frank Grünwald
Keyword(s):  
Dose Rate ◽  
Low Dose ◽  
Biological Effects ◽  
Survival Curve ◽  
Photon Radiation ◽  
High Dose ◽  
Survival Curves ◽  
Photon Irradiation ◽  
Low Dose Rate ◽  
Accumulated Dose

Abstract Aim Aim of the study was to determine the effects of the β--emitter 186Re and 662 keV photon radiation in order to compare the biological effects of low dose rate (186Re) to high dose rate irradiation. Methods Prae-B-lymphocytes were exposed to 662 keV photon radiation or incubated with a liquid solution of 186Re. Cell count and viability were compared over the observation period of seven days, survival curves constructed and analysed at time of lowest cell-viability. Results Biphasic cell survival curves resulted for both radiation types. Survival curves were obtained at 24 h for photon radiation and 72 h for 186Re. The biphasic survival curve after photon radiation exposure can be explained by radiation hypersensitivity at doses below 1 Gy resulting in a D0 of 3.3 Gy. Doses exceeding 1.0 Gy showed a D0 of 10 Gy. The biphasic survival curve in case of 186Re incubation represents repair of sub lethal damage in the first section of the curve (D0 11.1 Gy) – in this case, biological effects of the β--emitter are attenuated by repair. Beyond an accumulated dose of 1.6 Gy, 186Re showed a steeper slope with a D0 of 4 Gy, corresponding to 2.5 times higher biological effects compared to acute photon irradiation (10 Gy). Conclusion Low dose rate radiation resulted in low biological effects at low doses. There is a threshold of accumulated dose above which biological effects of 186Re-incubation exceed those of photon irradiation.

Acetaminophen: Neonatal hepatotoxicity due to late pregnancy exposure

1987 ◽  
Vol 45 ◽  
pp. 718-719
Author(s):  
G.A. Miranda ◽  
M.A. Arroyo ◽  
C.A. Lucio ◽  
M. Mongeotti ◽  
S.S. Poolsawat
Keyword(s):  
Low Dose ◽  
Fetal Liver ◽  
Late Pregnancy ◽  
Toxic Chemicals ◽  
Control Group ◽  
High Dose ◽  
Over The Counter ◽  
Liver And Kidney ◽  
Neonatal Liver ◽  
Childbearing Women

Exposure to drugs and toxic chemicals, during late pregnancy, is a common occurrence in childbearing women. Some studies have reported that more than 90% of pregnant women use at least 1 prescription; of this, 60% used more than one. Another study indicated that 80% of the consumed drugs were not prescribed, and of this figure, 95% were “over-the-counter” drugs. Acetaminophen, the safest of all over-the-counter drugs, has been reported to induce fetal liver necrosis in man and animals and to have abortifacient and embryocidal action in mice. This study examines the degree to which acetaminophen affects the neonatal liver and kidney, when a fatty diet is simultaneously fed to the mother during late pregnancy.Timed Swiss Webster female mice were gavaged during late pregnancy (days 16-19) with fat suspended acetaminophen at a high dose, HD = 84.50 mg/kg, and a low dose, LD = 42.25 mg/kg; a control group received fat alone.

Evaluation of hippocampus in rhesus monkeys after chronic (1-year) inhalation exposure to marijuana: I. Electron microscopy

1990 ◽  
Vol 48 (3) ◽  
pp. 398-399
Author(s):  
A.M. Andrews ◽  
S.W. Wilson ◽  
A.C. Scallet ◽  
S.F. Ali ◽  
J. Bailey ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Rhesus Monkeys ◽  
Low Dose ◽  
Inhalation Exposure ◽  
Synaptic Cleft ◽  
High Dose ◽  
Withdrawal Time ◽  
Treatment Groups ◽  
Ultrastructural Evidence ◽  
Male Rhesus

Exposure of rhesus monkeys (Macaca mulatta) to marijuana via inhalation or to intravenous delta-9-tetrahydrocannabinol (THC), reportedly caused ultrastructural evidence of increased synaptic width. Chronic marijuana smoke in a single rhesus monkey examined after a six month withdrawal time caused ultrastructure changes in the septal, hippocampal and amygdala regions; the synaptic cleft was widened, electron opaque material was found in the cleft and in the pre- and postsynaptic regions, with some clumping of the synaptic vesicles. The objective of our study was to assess neuropathological alterations produced by chronic inhalation of marijuana smoke.Nineteen male rhesus monkeys, 3-5 years of age and weighing 3-8 kg, were divided into four treatment groups: a) sham control, b) placebo smoke (7 days/ week) c) low dose marijuana (2 times/week with 5 days/week sham) and d) high dose marijuana (7 times/week). A smoke exposure consisted of smoke from one cigarette (2.6% THC) burned down to 10 mm butt length. Smoke was administered via smoke generator (ADL II, Arthur D. Little, Inc. Cambridge, MA) and nose-mouth only masks (local production) equipped with one-way valves.

Benefit/Risk Profile of Combined Antiplatelet Therapy with Ticlopidine and Aspirin

1991 ◽  
Vol 65 (05) ◽  
pp. 504-510 ◽  
Author(s):  
Raffaele De Caterina ◽  
Rosa Sicari ◽  
Walter Bernini ◽  
Guido Lazzerini ◽  
Giuliana Buti Strata ◽  
...  
Keyword(s):  
Platelet Function ◽  
Low Dose ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Stable Coronary Artery Disease ◽  
High Dose ◽  
Single Drug ◽  
Before And After ◽  
Serum Thromboxane ◽  
Artery Disease

SummaryTiclopidine (T) and aspirin (ASA) are two antiplatelet drugs both capable of prolonging bleeding time (BT), with a different mechanism of action. A synergism in BT prolongation has been reported and is currently considered an argument for not recommending their combination. However, a profound suppression of platelet function might be a desirable counterpart of a marked prolongation of BT, with a possible use in selected clinical situations. We therefore studied ex vivo platelet function (aggregation by ADP 0.5-1-2.5 μM; adrenaline 0.75-2.5 μM; collagen 1.5-150 μg/ml; arachidonic acid 1 mM; PAF 1 μM; adrenaline 0.17 μM + ADP 0.62 μM; serum thromboxane ([TX]B2 generation) and BT (Mielke) in 6 patients with stable coronary artery disease receiving such combination. Patients underwent sequential laboratory evaluations at baseline, after 7 days of T 250 mg b.i.d., before and after the intravenous administration of ASA 500 mg, respectively, and, finally, after a minimum of 7 days of sole ASA oral administration (50 mg/day). The experimental design, therefore, allowed a comparison of T and ASA effects (2nd and 4th evaluation), and an assessment of the combination effect (3rd evaluation). Platelet aggregation in response to all doses of ADP was depressed more by T than by ASA. Conversely, responses to adrenaline, and arachidonate were affected more by ASA than by T. For all other agents, differences were not significant. T + ASA combination was more effective (p <0.05) than either treatment alone in depressing responses to high-dose collagen (% over control, mean ± SEM: T: 95 ± 3; ASA: 96 ± 5; T + ASA: 89 ± 4). Serum TXB2 (basal, ng/ml: 380 ± 54) did not change with T (372 ± 36), dropped to <1 ng/ml on ASA injection and slightly re-increased to 9.1 ± 3.1 ng/ml on oral low-dose ASA. BT (basal 7.4 ± 0.6 min) was affected similarly by T (9.2 ± 0.8) or ASA (9.7 ± 0.9) alone, but increased to 15.0 ± 0.7 min on combination treatment (106% increase over control). Thus, the strong synergism in BT prolongation by ASA-T combination has a counterpart in the inhibition of platelet function in response to strong stimuli such as high-dose collagen, not otherwise affected significantly by single-drug treatment. This effect is a possible rationale for the clinical evaluation of T + ASA combination.

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