Quantified retrospective biomonitoring of fetal and infant elemental exposure using LA-ICP-MS analysis of deciduous dentin in three contrasting human cohorts.

BACKGROUND: Spatial elemental analysis of deciduous tooth dentin combined with odontochronological estimates can provide an early life (in utero to ~2 years of age) history of inorganic element exposure and status. OBJECTIVE: To demonstrate the importance of data normalization to a certified reference material to enable between-study comparisons, using populations with assumed contrasting elemental exposures. METHODS: We used laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) of dentin to derive a history of elemental composition from three distinct cohort studies: a present day rural cohort, (the New Hampshire Birth Cohort Study (NHBCS; N = 154)), an historical cohort from an urban area (1958-1970), (the St. Louis Baby Tooth Study (SLBT; N = 78)), and a present-day Nigerian cohort established to study maternal HIV transmission (Dental caries and its association with Oral Microbiomes and HIV in young children-Nigeria (DOMHaIN; N = 31)). RESULTS: We report Li, Al, Mn, Cu, Zn, Sr, Ba and Pb concentrations (µg/g) and qualitatively examine As, Cd and Hg across all three cohorts. Rates of detection were highest, both overall and for each cohort individually, for Zn, Sr, Ba and Li. Zinc was detected in 100% of samples and was stably present in teeth at a concentration range of 64 - 86 µg/g. Mercury, As and Cd detection rates were the lowest, and had high variability within individual ablated spots. We found the highest concentrations of Pb in the pre- and postnatal dentin of the SLBT cohort, consistent with the prevalent use of Pb as an additive to gasoline prior to 1975. The characteristic decline in Mn after the second trimester was observed in all cohorts. IMPACT: Spatially resolved elemental analysis of deciduous teeth combined with methods for estimating crown formation times can be used to reconstruct an early-life history of elemental exposure inaccessible via other biomarkers. Quantification of data into absolute values using an external standard reference material has not been conducted since 2012, preventing comparison between studies, a common and highly informative component of epidemiology. We demonstrate, with three contrasting populations, that absolute quantification produces data with the lowest variability, compares well with available data and recommends that future tooth biomarker studies report data in this way.

Early-life participation in cognitively stimulating activities and risk of depression and anxiety in late life.

BACKGROUND: Early-life stressful experiences are associated with increased risk of adverse psychological outcomes in later life. However, much less is known about associations between early-life positive experiences, such as participation in cognitively stimulating activities, and late-life mental health. We investigated whether greater engagement in cognitively stimulating activities in early life is associated with lower risk of depression and anxiety in late life. METHODS: We surveyed former participants of the St. Louis Baby Tooth study, between 22 June 2021 and 25 March 2022 to collect information on participants' current depression/anxiety symptoms and their early-life activities (N = 2187 responded). A composite activity score was created to represent the early-life activity level by averaging the frequency of self-reported participation in common cognitively stimulating activities in participants' early life (age 6, 12, 18), each rated on a 1 (least frequent) to 5 (most frequent) point scale. Depression/anxiety symptoms were measured by Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder Screener (GAD-7). We used logistic regressions to estimate odds ratios (OR) and 95% confidence intervals (CI) of outcome risk associated with frequency of early-life activity. RESULTS: Each one-point increase in the early-life composite cognitive activity score was associated with an OR of 0.54 (95% CI 0.38-0.77) for late-life depression and an OR of 0.94 (95% CI 0.61-1.43) for late-life anxiety, adjusting for age, sex, race, parental education, childhood family structure, and socioeconomic status. CONCLUSIONS: More frequent participation in cognitively stimulating activities during early life was associated with reduced risk of late-life depression.

Strontium-90 in Baby Teeth as a Basis for Estimating U.S. Cancer Deaths From Nuclear Weapons Fallout.

Nuclear weapons testing in the atmosphere during the 1950s and 1960s deposited fallout throughout the world, exposing all humans to food and water before the Limited Test Ban Treaty ended large-scale tests. The largest effort to measure in vivo fallout in humans, performed by Washington University (USA), collected over 300,000 deciduous teeth to document a sustained increase in Strontium-90 (Sr-90) during testing and a sharp decline after the test ban. Sr-90 patterns and trends in teeth were consistent with those of bones and milk. Sr-90 is still detectable in about 100,000 of the teeth, which were never tested. Tooth donors were born during atmospheric testing (1946-1965) and thus exposed to fallout in utero and during infancy/childhood, when exposures pose the greatest health risk. Preliminary analysis of global fallout's health risk in the United States indicates recent cancer mortality in several high-fallout areas exceeded that of states with the lowest fallout, peaking for the cohort born in the early 1960s, when fallout was highest. These findings support subsequent measurement of Sr-90 in deciduous teeth of persons who died of diseases such as cancer, along with controls, a novel approach to assessing fallout hazards.

Comparative efficiency analysis of fiber-array and conventional beam director systems in volume turbulence.

The performance of two prominent laser beam projection system types is analyzed through wave-optics numerical simulations for various atmospheric turbulence conditions, propagation distances, and adaptive optics (AO) mitigation techniques. Comparisons are made between different configurations of both a conventional beam director (BD) using a monolithic-optics-based Cassegrain telescope and a fiber-array BD that uses an array of densely packed fiber collimators. The BD systems considered have equal input power and aperture diameters. The projected laser beam power inside the Airy size disk at the target plane is used as the performance metric. For the fiber-array system, both incoherent and coherent beam combining regimes are considered. We also present preliminary results of side-by-side atmospheric beam projection experiments over a 7-km propagation path using both the AO-enhanced beam projection system with a Cassegrain telescope and the coherent fiber-array BD composed of 21 densely packed fiber collimators. Both wave-optics numerical simulation and experimental results demonstrate that, for similar system architectures and turbulence conditions, coherent fiber-array systems are more efficient in mitigation of atmospheric turbulence effects and generation of a hit spot of the smallest possible size on a remotely located target.

Deep turbulence effects mitigation with coherent combining of 21 laser beams over 7 km.

We demonstrate coherent beam combining and adaptive mitigation of atmospheric turbulence effects over 7 km under strong scintillation conditions using a coherent fiber array laser transmitter operating in a target-in-the-loop setting. The transmitter system is composed of a densely packed array of 21 fiber collimators with integrated capabilities for piston, tip, and tilt control of the outgoing beams wavefront phases. A small cat's-eye retro reflector was used for evaluation of beam combining and turbulence compensation performance at the target plane, and to provide the feedback signal for control of piston and tip/tilt phases of the transmitted beams using the stochastic parallel gradient descent maximization of the power-in-the-bucket metric.

Evaluating for a geospatial relationship between radon levels and thyroid cancer in Pennsylvania.

OBJECTIVES/HYPOTHESIS: To determine whether there is an association between radon levels and the rise in incidence of thyroid cancer in Pennsylvania. STUDY DESIGN: Epidemiological study of the state of Pennsylvania. METHODS: We used information from the Pennsylvania Cancer Registry and the Pennsylvania Department of Energy. From the registry, information regarding thyroid incidence by county and zip code was recorded. Information regarding radon levels per county was recorded from the state. Poisson regression models were fit predicting county-level thyroid incidence and change as a function of radon/lagged radon levels. To account for measurement error in the radon levels, a Bayesian Model extending the Poisson models was fit. Geospatial clustering analysis was also performed. RESULTS: No association was noted between cumulative radon levels and thyroid incidence. In the Poisson modeling, no significant association was noted between county radon level and thyroid cancer incidence (P = .23). Looking for a lag between the radon level and its effect, no significant effect was seen with a lag of 0 to 6 years between exposure and effect (P = .063 to P = .59). The Bayesian models also failed to show a statistically significant association. A cluster of high thyroid cancer incidence was found in western Pennsylvania. CONCLUSIONS: Through a variety of models, no association was elicited between annual radon levels recorded in Pennsylvania and the rising incidence of thyroid cancer. However, a cluster of thyroid cancer incidence was found in western Pennsylvania. Further studies may be helpful in looking for other exposures or associations.

Thyroid cancer characteristics in the population surrounding Three Mile Island.

OBJECTIVES/HYPOTHESIS: To determine differences in disease characteristics between the thyroid cancer populations in the area around the Three Mile Island (TMI) nuclear power plant and the rest of the state of Pennsylvania. STUDY DESIGN: Retrospective cross-sectional study. METHODS: Data from the Pennsylvania Cancer Registry from 1985 to 2008 were reviewed and information regarding age at diagnosis, sex, race, residential status, county of residence, thyroid pathology, thyroid surgery, and staging was recorded. Dauphin, Lancaster, and York counties were defined as the TMI area. RESULTS: Records of 26,357 thyroid cancer patients were reviewed, with 2,611 patients within the TMI area. A higher proportion of papillary thyroid cancer (P < .001) and lower proportion of follicular thyroid cancer (P < .001) were noted in the TMI area population. Thyroid cancer cases from the TMI area were found to be more likely to be diagnosed before the age of 65 years (P < .001), be Pennsylvania born (P < .001), be well differentiated (P < .001), be <10 mm in size (P < .001), and be localized without spread (P < .001). Although the TMI area shows a higher incidence of thyroid cancer as compared to the rest of the state, this was not statistically significant. CONCLUSIONS: The TMI population showed a higher proportion of papillary thyroid cancer and less aggressive pathology and earlier diagnosis compared to the rest of Pennsylvania. No statistically significant difference in thyroid cancer incidence was noted. Overall, the study does not show a clear link with more advanced thyroid cancer and proximity to the TMI nuclear reactors.

An unexpected mortality increase in the United States follows arrival of the radioactive plume from Fukushima: is there a correlation?

The multiple nuclear meltdowns at the Fukushima plants beginning on March 11, 2011, are releasing large amounts of airborne radioactivity that has spread throughout Japan and to other nations; thus, studies of contamination and health hazards are merited. In the United States, Fukushima fallout arrived just six days after the earthquake, tsunami, and meltdowns. Some samples of radioactivity in precipitation, air, water, and milk, taken by the U.S. government, showed levels hundreds of times above normal; however, the small number of samples prohibits any credible analysis of temporal trends and spatial comparisons. U.S. health officials report weekly deaths by age in 122 cities, about 25 to 35 percent of the national total. Deaths rose 4.46 percent from 2010 to 2011 in the 14 weeks after the arrival of Japanese fallout, compared with a 2.34 percent increase in the prior 14 weeks. The number of infant deaths after Fukushima rose 1.80 percent, compared with a previous 8.37 percent decrease. Projecting these figures for the entire United States yields 13,983 total deaths and 822 infant deaths in excess of the expected. These preliminary data need to be followed up, especially in the light of similar preliminary U.S. mortality findings for the four months after Chernobyl fallout arrived in 1986, which approximated final figures.

Elevated in vivo strontium-90 from nuclear weapons test fallout among cancer decedents: a case-control study of deciduous teeth.

Risks to health from large-scale atmospheric nuclear weapons testing are still relatively unknown. A sample of 85,000 deciduous teeth collected from Americans born during the bomb-testing years assessed risk by in vivo measurement of residual strontium-90 (Sr-90) concentrations, using liquid scintillation spectrometry. The authors' analysis included 97 deciduous teeth from persons born between 1959 and 1961 who were diagrosed with cancer, and 194 teeth of matched controls. Average Sr-90 in teeth of persons who died of cancer was significantly greater than for controls (OR = 2.22; p < 0.04). This discovery suggests that many thousands have died or will die of cancer due to exposure to fallout, far more than previously believed.

Geographic variation in U.S. thyroid cancer incidence and a cluster near nuclear reactors in New Jersey, New York, and Pennsylvania.

In the United States, thyroid cancer incidence (along with liver cancer) is increasing more rapidly than any other malignancy, rising nearly threefold from 1980 to 2006. Improved diagnosis has been proposed by some as the major reason for this change, while others contend that additional factors also account for the increase. Among U.S. states, 2001-2005 age-adjusted thyroid cancer incidence rates vary from 5.4 to 12.8 per 100,000. County-specific incidence data, available for the first time, document that most U.S. counties with the highest thyroid cancer incidence are in a contiguous area of eastern Pennsylvania, New Jersey, and southern New York State. Exposures to radioactive iodine emissions from 16 nuclear power reactors within a 90-mile radius in this area indicate that these emissions are a likely etiological factor in rising thyroid cancer incidence rates.

Excess infant mortality after nuclear plant startup in rural Mississippi.

In the United States, utility companies have recently begun ordering new nuclear power reactors, the first such orders in the country since 1978. One potential site would be the Grand Gulf plant near Port Gibson, Mississippi. In 1983-1984, the first two years in which the existing Grand Gulf reactor operated, significant increases were observed in local rates of infant deaths (+35.3%) and fetal deaths (+57.8%). Local infant mortality remained elevated for the next two decades. These changes match those experienced in the same five local counties during atomic bomb testing in the 1950s and 1960s. This report examines potential reasons why an indigent, largely African American community may be at higher risk than other populations from exposure to an environmental toxin such as radiation. It also considers potential health risks posed by new reactors at Grand Gulf.

A short latency between radiation exposure from nuclear plants and cancer in young children.

Previous reports document a short latency of cancer onset in young children exposed to low doses of radioactivity. The standard mortality ratio (SMR) for cancer in children dying before age ten rose in the period 6-10 years after the Three Mile Island and Chernobyl accidents in populations most exposed to fallout. SMRs near most nuclear power plants were elevated 6-10 years after startup, particularly for leukemia. Cancer incidence in children under age ten living near New York and New Jersey nuclear plants increased 4-5 years after increases in average strontium-90 in baby teeth, and declined 4-5 years after Sr-90 averages dropped. The assumption that Sr-90 and childhood cancer are correlated is best supported for a supralinear dose-response, meaning the greatest per-dose risks are at the lowest doses. Findings document that the very young are especially susceptible to adverse effects of radiation exposure, even at relatively low doses.

Flowing cells through pulsed electric fields efficiently purges stem cell preparations of contaminating myeloma cells while preserving stem cell function.

Autologous stem cell transplantation, in the setting of hematologic malignancies such as lymphoma, improves disease-free survival if the graft has undergone tumor purging. Here we show that flowing hematopoietic cells through pulsed electric fields (PEFs) effectively purges myeloma cells without sacrificing functional stem cells. Electric fields can induce irreversible cell membrane pores in direct relation to cell diameter, an effect we exploit in a flowing system appropriate for clinical scale. Multiple myeloma (MM) cell lines admixed with human bone marrow (BM) or peripheral blood (PB) cells were passed through PEFs at 1.35 kV/cm to 1.4 kV/cm, resulting in 3- to 4-log tumor cell depletion by flow cytometry and 4.5- to 6-log depletion by tumor regrowth cultures. Samples from patients with MM gave similar results by cytometry. Stem cell engraftment into nonobese diabetic-severe combined immunodeficient (NOD/SCID)/beta2m-/- mice was unperturbed by PEFs. Flowing cells through PEFs is a promising technology for rapid tumor cell purging of clinical progenitor cell preparations.

An unexpected rise in strontium-90 in US deciduous teeth in the 1990s.

For several decades, the United States has been without an ongoing program measuring levels of fission products in the body. Strontium-90 (Sr-90) concentrations in 2089 deciduous (baby) teeth, mostly from persons living near nuclear power reactors, reveal that average levels rose 48.5% for persons born in the late 1990s compared to those born in the late 1980s. This trend represents the first sustained increase since the early 1960s, before atmospheric weapons tests were banned. The trend was consistent for each of the five states for which at least 130 teeth are available. The highest averages were found in southeastern Pennsylvania, and the lowest in California (San Francisco and Sacramento), neither of which is near an operating nuclear reactor. In each state studied, the average Sr-90 concentration is highest in counties situated closest to nuclear reactors. It is likely that, 40 years after large-scale atmospheric atomic bomb tests ended, much of the current in-body radioactivity represents nuclear reactor emissions.

Elevated childhood cancer incidence proximate to U.S. nuclear power plants.

Numerous reports document elevated cancer rates among children living near nuclear facilities in various nations. Little research has examined U.S. rates near the nation's 103 operating reactors. This study determined that cancer incidence for children < 10 yr of age who live within 30 mi (48 km) of each of 14 nuclear plants in the eastern United States (49 counties with a population > 16.8 million) exceeds the national average. The excess 12.4% risk suggests that 1 in 9 cancers among children who reside near nuclear reactors is linked to radioactive emissions. If cancer incidence in 5 western states is used as a baseline, the ratio is closer to 1 in 5. Incidence is particularly elevated for leukemia. Childhood cancer mortality exceeds the national average in 7 of the 14 study areas.

Infant death and childhood cancer reductions after nuclear plant closings in the United States.

Subsequent to 1987, 8 U.S. nuclear plants located at least 113 km from other reactors ceased operations. Strontium-90 levels in local milk declined sharply after closings, as did deaths among infants who had lived downwind and within 64 km of each plant. These reductions occurred during the first 2 yr that followed closing of the plants, were sustained for at least 6 yr, and were especially pronounced for birth defects. Trends in infant deaths in proximate areas not downwind, and more than 64 km from the closed plants, were not different from the national patterns. In proximate areas for which data were available, cancer incidence in children younger than 5 yr of age fell significantly after the shutdowns. Changes in health following nuclear reactor closings may help elucidate the relationship between low-dose radiation exposure and disease.