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BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death worldwide. It has been known for some considerable time that radiation is associated with excess risk of CVD. A recent systematic review of radiation and CVD highlighted substantial inter-study heterogeneity in effect, possibly a result of confounding or modifications of radiation effect by non-radiation factors, in particular by the major lifestyle/environmental/medical risk factors and latent period. METHODS: We assessed effects of confounding by lifestyle/environmental/medical risk factors on radiation-associated CVD and investigated evidence for modifying effects of these variables on CVD radiation dose-response, using data assembled for a recent systematic review. RESULTS: There are 43 epidemiologic studies which are informative on effects of adjustment for confounding or risk modifying factors on radiation-associated CVD. Of these 22 were studies of groups exposed to substantial doses of medical radiation for therapy or diagnosis. The remaining 21 studies were of groups exposed at much lower levels of dose and/or dose rate. Only four studies suggest substantial effects of adjustment for lifestyle/environmental/medical risk factors on radiation risk of CVD; however, there were also substantial uncertainties in the estimates in all of these studies. There are fewer suggestions of effects that modify the radiation dose response; only two studies, both at lower levels of dose, report the most serious level of modifying effect. CONCLUSIONS: There are still large uncertainties about confounding factors or lifestyle/environmental/medical variables that may influence radiation-associated CVD, although indications are that there are not many studies in which there are substantial confounding effects of these risk factors.

BACKGROUND: Many high-dose groups demonstrate increased leukaemia risks, with risk greatest following childhood exposure; risks at low/moderate doses are less clear. METHODS: We conducted a pooled analysis of the major radiation-associated leukaemias (acute myeloid leukaemia (AML) with/without the inclusion of myelodysplastic syndrome (MDS), chronic myeloid leukaemia (CML), acute lymphoblastic leukaemia (ALL)) in ten childhood-exposed groups, including Japanese atomic bomb survivors, four therapeutically irradiated and five diagnostically exposed cohorts, a mixture of incidence and mortality data. Relative/absolute risk Poisson regression models were fitted. RESULTS: Of 365 cases/deaths of leukaemias excluding chronic lymphocytic leukaemia, there were 272 AML/CML/ALL among 310,905 persons (7,641,362 person-years), with mean active bone marrow (ABM) dose of 0.11 Gy (range 0-5.95). We estimated significant (P

There is direct evidence of risks at moderate and high levels of radiation dose for highly radiogenic cancers such as leukaemia and thyroid cancer. For many cancer sites, however, it is necessary to assess risks via extrapolation from groups exposed at moderate and high levels of dose, about which there are substantial uncertainties. Crucial to the resolution of this area of uncertainty is the modelling of the dose-response relationship and the importance of both systematic and random dosimetric errors for analyses in the various exposed groups. It is well recognised that measurement error can alter substantially the shape of this relationship and hence the derived population risk estimates. Particular attention has been devoted to the issue of shared errors, common in many datasets, and particularly important in occupational settings. We propose a modification of the regression calibration method which is particularly suited to studies in which there is a substantial amount of shared error, and in which there may also be curvature in the true dose response. This method can be used in settings where there is a mixture of Berkson and classical error. In fits to synthetic datasets in which there is substantial upward curvature in the true dose response, and varying (and sometimes substantial) amounts of classical and Berkson error, we show that the coverage probabilities of all methods for the linear coefficient [Formula: see text] are near the desired level, irrespective of the magnitudes of assumed Berkson and classical error, whether shared or unshared. However, the coverage probabilities for the quadratic coefficient [Formula: see text] are generally too low for the unadjusted and regression calibration methods, particularly for larger magnitudes of the Berkson error, whether this is shared or unshared. In contrast Monte Carlo maximum likelihood yields coverage probabilities for [Formula: see text] that are uniformly too high. The extended regression calibration method yields coverage probabilities that are too low when shared and unshared Berkson errors are both large, although otherwise it performs well, and coverage is generally better than these other three methods. A notable feature is that for all methods apart from extended regression calibration the estimates of the quadratic coefficient [Formula: see text] are substantially upwardly biased.

Predation pressure and herbivory exert cascading effects on coral reef health and stability. However, the extent of these cascading effects can vary considerably across space and time. This variability is likely a result of the complex interactions between coral reefs' biotic and abiotic dimensions. A major biological component that has been poorly integrated into the reefs' trophic studies is the microbial community, despite its role in coral death and bleaching susceptibility. Viruses that infect bacteria can control microbial densities and may positively affect coral health by controlling microbialization. We hypothesize that viral predation of bacteria has analogous effects to the top-down pressure of macroorganisms on the trophic structure and reef health. Here, we investigated the relationships between live coral cover and viruses, bacteria, benthic algae, fish biomass, and water chemistry in 110 reefs spanning inhabited and uninhabited islands and atolls across the Pacific Ocean. Statistical learning showed that the abundance of turf algae, viruses, and bacteria, in that order, were the variables best predicting the variance in coral cover. While fish biomass was not a strong predictor of coral cover, the relationship between fish and corals became apparent when analyzed in the context of viral predation: high coral cover (> 50%) occurred on reefs with a combination of high predator fish biomass (sum of sharks and piscivores > 200 g m-2) and high virus-to-bacteria ratios (> 10), an indicator of viral predation pressure. However, these relationships were non-linear, with reefs at the higher and lower ends of the coral cover continuum displaying a narrow combination of abiotic and biotic variables, while reefs at intermediate coral cover showed a wider range of parameter combinations. The results presented here support the hypothesis that viral predation of bacteria is associated with high coral cover and, thus, coral health and stability. We propose that combined predation pressures from fishes and viruses control energy fluxes, inhibiting the detrimental accumulation of ecosystem energy in the microbial food web.

BackgroundWhile there is a robust literature on environmental exposure to iodine-131 (131I) in childhood and adolescence and the risk of thyroid cancer and benign nodules, little is known about its effects on thyroid volume.MethodsTo assess the effect of 131I dose to the thyroid on the volume of the thyroid gland, we examined the data from the baseline screening of the Belarusian-American Cohort Study of residents of Belarus who were exposed to the Chernobyl fallout at ages ≤18 years. Thyroid dose estimates were based on individual thyroid activity measurements made shortly after the accident and dosimetric data from questionnaires obtained 10-15 years later at baseline screening. During baseline screening, thyroid gland volume was assessed from thyroid ultrasound measurements. The association between radiation dose and thyroid volume was modeled using linear regression where radiation dose was expressed with power terms to address non-linearity. The model was adjusted for attained age, sex, and place of residence, and their modifying effects were examined.ResultsThe analysis was based on 10,703 subjects. We found a statistically significant positive association between radiation dose and thyroid volume (P

There is limited evidence that non-leukaemic lymphoid malignancies are radiogenic. As radiation-related cancer risks are generally higher after childhood exposure, we analysed pooled lymphoid neoplasm data in nine cohorts first exposed to external radiation aged  0.4). In six cohorts with estimates of lymphatic tissue dose, borderline significant increased risks (p-trend = 0.02-0.07) were observed for NHL + CLL, NHL, and CLL. Further pooled epidemiological studies are needed with longer follow-up, central outcome review by expert hematopathologists, and assessment of radiation doses to lymphoid tissues.

Abstract Thyroid enlargement can cause problems with swallowing or breathing and a decrease in accuracy of screening for thyroid cancer. Exposure to radioactive iodines after the 1986 Chernobyl accident is known to increase risk of thyroid cancer in those exposed at a young age, but little is known about its effects on thyroid volume, which could have important clinical implications. The objective of this study is to characterize the dose-response association between iodine-131 (131I) exposure and thyroid volume using data from a Belarusian-American cohort study of residents of Belarus exposed during childhood. Persons exposed to Chernobyl fallout in Belarus at the age of 18 years or younger had individual 131I doses to the thyroid gland estimated from direct thyroid activity measurements, radioecological and biokinetic models, and interview data on whereabouts and dietary habits collected during baseline screening in 1996-2001 (N=11,970; median age 21 years). Thyroid volume was estimated from thyroid ultrasound measurements during screening. Individuals with diagnoses of benign or malignant tumors of thyroid gland, any thyroid surgery or aplasia, and missing thyroid volume measurements were excluded (n=1,104). Dose and thyroid volume were log-transformed due to right-skewed distributions. We used a multivariable linear regression to estimate the dose-response association between 131I dose to the thyroid and thyroid volume accounting for confounding effects of sex, age at screening, and place of residence at the time of screening, a proxy for endemic iodine deficiency. To examine nonlinear effects, we added a quadratic term for the log-transformed dose. Among 10,866 participants, dose to thyroid ranged from 0.0005 to 39 gray (Gy) (median=0.3 Gy). In a linear regression model adjusted for confounders, log thyroid volume was best described by a linear-quadratic function of log dose (p

A meta-analytic summary effect estimate often is calculated as an inverse-variance-weighted average of study-specific estimates of association. The variances of published estimates of association often are derived from their associated confidence intervals under assumptions typical of Wald-type statistics, such as normality of the parameter. However, in some research areas, such as radiation epidemiology, epidemiological results typically are obtained by fitting linear relative risk models, and associated likelihood-based confidence intervals are often asymmetric; consequently, reasonable estimates of variances associated with study-specific estimates of association may be difficult to infer from the standard approach based on the assumption of a Wald-type interval. Here, a novel method is described for meta-analysis of published results from linear relative risk models that uses a parametric transformation of published results to improve on the normal approximation used to assess confidence intervals. Using simulations, it is illustrated that the meta-analytic summary obtained using the proposed approach yields less biased summary estimates, with better confidence interval coverage, than the summary obtained using the more classical approach to meta-analysis. The proposed approach is illustrated using a previously published example of meta-analysis of epidemiological findings regarding circulatory disease following exposure to low-level ionizing radiation.

Traditionally, medicine has held that some human body sites are sterile and that the introduction of microbes to these sites results in infections. This paradigm shifted significantly with the discovery of the human microbiome and acceptance of these commensal microbes living across the body. However, the central nervous system (CNS) is still believed by many to be sterile in healthy people. Using culture-independent methods, we examined the virome of cerebrospinal fluid (CSF) from a cohort of mostly healthy human subjects. We identified a community of DNA viruses, most of which were identified as bacteriophages. Compared to other human specimen types, CSF viromes were not ecologically distinct. There was a high alpha diversity cluster that included feces, saliva, and urine, and a low alpha diversity cluster that included CSF, body fluids, plasma, and breast milk. The high diversity cluster included specimens known to have many bacteria, while other specimens traditionally assumed to be sterile formed the low diversity cluster. There was an abundance of viruses shared among CSF, breast milk, plasma, and body fluids, while each generally shared less with urine, feces, and saliva. These shared viruses ranged across different virus families, indicating that similarities between these viromes represent more than just a single shared virus family. By identifying a virome in the CSF of mostly healthy individuals, it is now less likely that any human body site is devoid of microbes, which further highlights the need to decipher the role that viral communities may play in human health.

Background: Chronic spontaneous urticaria (CSU) is a common, debilitating skin disorder characterized by recurring episodes of raised, itchy and sometimes painful wheals lasting longer than 6 weeks. CSU is mediated by mast cells which are absent from peripheral blood. However, lineage−CD34hiCD117int/hiFcεRI+ cells in blood have previously been shown to represent a mast cell precursor. Methods: We enumerated FcεRI−, FcεRI+ and FcεRIhi lineage−CD34+CD117+ cells using flow cytometry in blood of patients with CSU (n = 55), including 12 patients receiving omalizumab and 43 not receiving omalizumab (n = 43). Twenty‐two control samples were studied. Disease control and patient response to omalizumab was evaluated using the urticaria control test. We performed single‐cell RNA sequencing (scRNA‐Seq) on lineage−CD34hiCD117hi blood cells from a subset of patients with CSU (n = 8) and healthy controls (n = 4). Results: CSU patients had more lineage−CD34+CD117+FcεRI+ blood cells than controls. Lineage−CD34+CD117+FcεRI+ cells were significantly higher in patients with CSU who had an objective clinical response to omalizumab when compared to patients who had poor disease control 90 days after initiation of omalizumab. scRNA‐Seq revealed that lineage−CD34+CD117+FcεRI+ cells contained both lymphoid and myeloid progenitor lineages, with omalizumab responsive patients having proportionally more myeloid progenitors. The myeloid progenitor lineage contained small numbers of true mast cell precursors along with more immature FcεRI− and FcεRI+ myeloid progenitors. Conclusion: Increased blood CD34+CD117+FcεRI+ cells may reflect enhanced bone marrow egress in the setting of CSU. High expression of these cells strongly predicts better clinical responses to the anti‐IgE therapy, omalizumab. [ABSTRACT FROM AUTHOR]

In this article we review the history of key epidemiological studies of populations exposed to ionizing radiation. We highlight historical and recent findings regarding radiation-associated risks for incidence and mortality of cancer and non-cancer outcomes with emphasis on study design and methods of exposure assessment and dose estimation along with brief consideration of sources of bias for a few of the more important studies. We examine the findings from the epidemiological studies of the Japanese atomic bomb survivors, persons exposed to radiation for diagnostic or therapeutic purposes, those exposed to environmental sources including Chornobyl and other reactor accidents, and occupationally exposed cohorts. We also summarize results of pooled studies. These summaries are necessarily brief, but we provide references to more detailed information. We discuss possible future directions of study, to include assessment of susceptible populations, and possible new populations, data sources, study designs and methods of analysis. [ABSTRACT FROM AUTHOR]

Anthropogenic stressors like overfishing, land based runoff, and increasing temperatures cause the degradation of coral reefs, leading to the loss of corals and other calcifiers, increases in competitive fleshy algae, and increases in microbial pathogen abundance and hypoxia. To test the hypothesis that corals would be healthier by moving them off the benthos, a common garden experiment was conducted in which corals were translocated to midwater geodesic spheres (hereafter called Coral Reef Arks or Arks). Coral fragments translocated to the Arks survived significantly longer than equivalent coral fragments translocated to Control sites (i.e., benthos at the same depth). Over time, average living coral surface area and volume were higher on the Arks than the Control sites. The abundance and biomass of fish were also generally higher on the Arks compared to the Control sites, with more piscivorous fish on the Arks. The addition of Autonomous Reef Monitoring Structures (ARMS), which served as habitat for sessile and motile reef-associated organisms, also generally significantly increased fish associated with the Arks. Overall, the Arks increased translocated coral survivorship and growth, and exhibited knock-on effects such as higher fish abundance. [ABSTRACT FROM AUTHOR]

Over the last two decades, there has been emerging evidence suggesting that ionizing radiation exposures could be associated with elevated risks of cardiovascular disease (CVD), particularly ischemic heart disease (IHD). Excess CVD risks have been observed in a number of exposed groups, with generally similar risk estimates both at low and high radiation doses and dose rates. In 2014, we reported for the first time significantly higher risks of IHD mortality when radiation doses were delivered over a protracted period of time (an inverse dose-fractionation effect) in the Canadian Fluoroscopy Cohort Study. Here we review the current evidence on the dose-fractionation effect of radiation exposure, discuss potential implication for radiation protection policies and suggest further directions for research in this area. [ABSTRACT FROM AUTHOR]

Background: Although childhood exposure to radioactive iodine-131 (I-131) is an established risk factor for thyroid cancer, evidence for an association with thyroid nodules is less clear. The objective of this study is to evaluate the association between childhood I-131 exposure and prevalence of ultrasound-detected thyroid nodules overall and by nodule histology/cytology (neoplastic/suspicious/non-neoplastic), size (<10 mm/≥10 mm), and number (single/multiple). Methods: This is a cross-sectional study of radiation dose (mean = 0.53 gray, range: 0.0003–31 gray) and screen-detected thyroid nodules conducted in 1998–2000 (median population age 21.5 years) in a cohort of 13,243 residents of Ukraine who were under 18 years at the time of the Chornobyl accident on April 26, 1986. Excess odds ratios per gray (excess odds ratio [EOR]/Gy) and confidence intervals (CIs) were estimated using logistic regression. Results: Among 13,078 eligible individuals, we identified 358 (2.7%) with at least one thyroid nodule. Significantly increased dose–response associations were found for all nodules and nodule groups with doses <5 Gy except individuals with non-neoplastic nodules. Among individuals with doses <5 Gy, the EOR/Gy for neoplastic nodules (5.35; CI: 2.19–15.5) was significantly higher than for non-neoplastic nodules (0.24; CI: 0.07–0.74), but the EOR/Gy did not vary by nodule size or number. Conclusions: Childhood exposure to I-131 is associated with an increased risk of thyroid nodules detected 12–14 years following exposure, and the risk for neoplastic nodules is higher than for non-neoplastic nodules. Analyses of incident thyroid nodules may help clarify dose–response patterns by nodule characteristics and provide insights into thyroid nodule etiology. [ABSTRACT FROM AUTHOR]