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Radon is the second-leading cause of lung cancer worldwide. Most indoor exposure occurs by diffusion of soil gas. Radon is also found in well water, natural gas, and ambient air. Pennsylvania has high indoor radon concentrations; buildings are often tested

Background: Studies on human health and ecological effects of ionizing radiation are rapidly evolving as innovative technologies arise and the body of scientific knowledge grows. Structuring this information could effectively support the development of decision making tools and health risk models to complement current system of radiation protection. To this end, the adverse outcome pathway (AOP) approach is being explored as a means to consolidate the most relevant research to identify causation between exposure to a chemical or non-chemical stressor and disease or adverse effect progression. This tool is particularly important for low dose and low dose rate radiation exposures because of the latency and uncertainties in the biological responses at these exposure levels. To progress this aspect, it is essential to build a community of developers, facilitators, risk assessors (in the private sector and in government), policy-makers, and regulators who understand the strengths and weaknesses of, and how to appropriately utilize AOPs for consolidating our knowledge on the impact of low dose ionizing radiation. Through co-ordination with the Organisation of Economic Co-operation and Development (OECD) Nuclear Energy Agency (NEA) High-Level Group on Low-Dose Research (HLG-LDR) and OECD's AOP Programme, initiatives are under way to demonstrate this approach in radiation research and regulation. Among these, a robust communications strategy and stakeholder engagement will be essential. It will help establish best practices for AOPs in institutional project development and aid in dissemination for more efficient and timely uptake and use of AOPs. In this regard, on June 1, 2021, the Radiation and Chemical (Rad/Chem) AOP Joint Topical Group was formed as part of the initiative from the NEA's HLG-LDR. The topical group will work to develop a communication and engagement strategy to define the target audiences, establish the clear messages and identify the delivery and engagement platforms., Conclusion: The incorporation of the best science and better decision making should motive the radiation protection community to develop, refine and use AOPs, recognizing that their incorporation into radiation health risk assessments is critical for public health and environmental protection in the 21st century.

Almost all researchers, veterinarians, technicians, and students who work with laboratory animals are familiar with the laws, regulations, and policies governing the use of animals in their jurisdictions. This knowledge can be learned in an academic setting, but is often gained by "on the job" training conducted by facilities and institutions where these professionals work. In addition, these laws and regulations exist along a continuum; some countries have detailed and expansive animal law regimes, while others have few, if any laws. Accordingly, those who carry out research involving animals know local laws and regulations, but might not be aware of the laws, regulations, and policies of other jurisdictions.As scientific research becomes increasingly globalized, there is a growing need to gain an understanding of the laws and regulations of other countries. This article seeks to help bridge this gap in knowledge by defining 10 fundamental legal terms and concepts that are important in understanding the similarities and differences among the legal traditions of different nations and international agreements that impact laboratory animal research. The article focuses on Western law terms and concepts, because many laboratory animal statutes that have been enacted in these countries and international treaties and protocols can be viewed through a Western legal lens., (© The Author 2017. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Individuals differ in their susceptibility to radiogenic cancers, and there is evidence that this inter-individual susceptibility extends to HZE ion-induced carcinogenesis. Three components of individual risk: sex, age at exposure, and prior tobacco use, are already incorporated into the NASA cancer risk model used to determine safe days in space for US astronauts. Here, we examine other risk factors that could potentially be included in risk calculations. These include personal and family medical history, the presence of pre-malignant cells that could undergo malignant transformation as a consequence of radiation exposure, the results from phenotypic assays of radiosensitivity, heritable genetic polymorphisms associated with radiosensitivity, and postflight monitoring. Inclusion of these additional risk or risk reduction factors has the potential to personalize risk estimates for individual astronauts and could influence the determination of safe days in space. We consider how this type of assessment could be used and explore how the provisions of the federal Genetic Information Non-discrimination Act could impact the collection, dissemination and use of this information by NASA.

Recognizing the central importance of effective communication, education, and policy across all of the domains of radiation safety and radiation protection, the National Council on Radiation Protection and Measurements (NCRP) established a new committee in 2013. Program Area Committee 7 (PAC 7) was created to develop projects and provide guidance on "Radiation Education, Risk Communication, Outreach, and Policy." After identifying individuals with relevant expertise who were willing to serve, the Committee held its inaugural meeting in 2014. In 2015, the Committee increased its membership and began carrying out an expanded program of activities. One area of activity has involved providing input and feedback on risk communication issues to NCRP and other agencies. Another area of work has involved liaising with other NCRP committees (e.g., Council Committee 1 and PAC 3) to help incorporate psychosocial and risk communication issues into projects. Future efforts of NCRP's newest PAC are expected to include the development of authoritative reports and commentaries dealing with critical issues and challenges in radiation risk communication, education, and policy.

Background: Radon is the second-leading cause of lung cancer worldwide. Most indoor exposure occurs by diffusion of soil gas. Radon is also found in well water, natural gas, and ambient air. Pennsylvania has high indoor radon concentrations; buildings are often tested during real estate transactions, with results reported to the Department of Environmental Protection (PADEP)., Objectives: We evaluated predictors of indoor radon concentrations., Methods: Using first-floor and basement indoor radon results reported to the PADEP between 1987 and 2013, we evaluated associations of radon concentrations (natural log transformed) with geology, water source, building characteristics, season, weather, community socioeconomic status, community type, and unconventional natural gas development measures based on drilled and producing wells., Results: Primary analysis included 866,735 first measurements by building, with the large majority from homes. The geologic rock layer on which the building sat was strongly associated with radon concentration (e.g., Axemann Formation, median = 365 Bq/m3, IQR = 167-679 vs. Stockton Formation, median = 93 Bq/m3, IQR = 52-178). In adjusted analysis, buildings using well water had 21% higher concentrations (β = 0.191, 95% CI: 0.184, 0.198). Buildings in cities (vs. townships) had lower concentrations (β = -0.323, 95% CI: -0.333, -0.314). When we included multiple tests per building, concentrations declined with repeated measurements over time. Between 2005 and 2013, 7,469 unconventional wells were drilled in Pennsylvania. Basement radon concentrations fluctuated between 1987 and 2003, but began an upward trend from 2004 to 2012 in all county categories (p < 0.001), with higher levels in counties having ≥ 100 drilled wells versus counties with none, and with highest levels in the Reading Prong., Conclusions: Geologic unit, well water, community, weather, and unconventional natural gas development were associated with indoor radon concentrations. Future studies should include direct environmental measurement of radon, as well as building features unavailable for this analysis., Citation: Casey JA, Ogburn EL, Rasmussen SG, Irving JK, Pollak J, Locke PA, Schwartz BS. 2015. Predictors of indoor radon concentrations in Pennsylvania, 1989-2013. Environ Health Perspect 123:1130-1137; http://dx.doi.org/10.1289/ehp.1409014.

The past 50 y have seen substantial developments in radiation epidemiology, technology, dosimetry, regulations, and protection efforts. During the last five decades, radiation communication has also evolved, growing more sophisticated as communication science and practice have advanced and matured. This talk covers the trends in radiation protection over the past 50 y, illustrated by progress in science and practice of risk communication and changes in societal expectations, and examines challenges that will confront radiation risk communication in the future.

This paper is focused on summarizing the "lessons learned" from discussions at the 2010 NCRP Annual Meeting on effective communications on the subject of radiation benefits and risks in public exposures. Five main lessons learned are discussed in regard to effective methods of public communication: the use of new social media communication tools such as Facebook and Twitter, emergency situations that require rapid societal and personal messaging, medical radiological procedures where benefits must be described in comparison to long-term health risks of radiation exposures, and information that should be provided to stakeholders in situations such as environmental radionuclide contamination to which members of the public may be exposed. It is concluded that effective communications in which radiation benefits are contrasted with health risks of exposure are an important aspect of making and implementing decisions on employing radiation health protection procedures.

The Toxic Substances Control Act is the principal US law governing industrial chemicals. Over the past three and one half decades, it has become clear that a considerable toxicological information gap exists about chemicals in commerce. The current provisions of the US TSCA law have failed to fill, and perhaps even exacerbated, that gap. For at least the past 5 years, bills have been introduced before the US Congress to reauthorize TSCA.Filling the toxicological information gap has been one of the driving forces for this call for substantial change. This article describes efforts to modernize TSCA, with an emphasis on the new provisions that would be put into place if the legislation became law. The article shows that only by implementing a "replacement-first" strategy - a strategy that is not currently incorporated into TSCA reauthorization efforts - can TSCA modernization efforts potentially fill the toxic data voids.

In 2007, the U.S. National Academy of Sciences, National Research Council (NRC), issued the report Toxicity Testing in the 21st Century: A Vision and a Strategy. This report, which was commissioned by the U.S. Environmental Protection Agency (EPA), called for the U.S. EPA to develop a new approach for how this agency evaluates the toxicity of compounds. The report recommended that the agency move from its current testing system, which is based largely on traditional toxicology, to a testing system that is based primarily on human cell lines and in vitro systems. Successful implementation of the report's vision and strategy will require that scientists, lawyers, and policymakers work together to bridge the gap among disciplines. An important step in building this bridge requires an analysis of the U.S. legal system that frames toxicity testing. If the U.S. laws, regulations, and policies erect barriers that would prevent or impede the U.S. EPA adoption of the NRC vision and strategy, it is important to identify these challenges. At the same time, if existing laws, regulations, and policies are fertile ground for these recommendations, opportunities should be documented. This article discusses and evaluates the challenges and opportunities that arise under key provisions of one major U.S. toxics law, the Toxics Substances Control Act (TSCA).

The U.S. Department of Energy (U.S. DOE) sponsors a research program aimed at gaining a better understanding of how low-dose radiation affects cellular functioning and progression toward disease. There have been calls to incorporate into regulatory decision-making the scientific information that this program has produced. After a discussion of the evolution of radiation protection law and the weight-of-evidence approach that agencies employ, this paper offers some preliminary thoughts about how to approach this complex and important policy question. Three implementation challenges are identified and discussed. The first implementation challenge involves explaining low-dose effects in a systems biology model. The second challenge arises when issues of population susceptibility are juxtaposed against molecular and mechanistic studies, such as those that make up much of the U.S. DOE low-dose program. The third challenge concerns integrating the results of radiation epidemiology, especially epidemiologic studies among cohorts that are exposed to low dose and low-dose rate radiation, with the results of U.S. DOE low-dose studies.

Driven by differing statutory mandates and programmatic separation of regulatory responsibilities between federal, state, and tribal agencies, distinct chemical and radiation risk management strategies have evolved. In the field this separation poses real challenges since many of the major environmental risk management decisions we face today require the evaluation of both types of risks. Over the last decade, federal, state, and tribal agencies have continued to discuss their different approaches and explore areas where their activities could be harmonized. The current framework for managing public exposures to chemical carcinogens has been referred to as a "bottom up approach." Risk between 10(-4) and 10(-6) is established as an upper bound goal. In contrast, a "top down" approach that sets an upper bound dose limit and couples with site specific As Low As Reasonably Achievable Principle (ALARA), is in place to manage individual exposure to radiation. While radiation risk are typically managed on a cumulative basis, exposure to chemicals is generally managed on a chemical-by-chemical, medium-by-medium basis. There are also differences in the nature and size of sites where chemical and radiation contamination is found. Such differences result in divergent management concerns. In spite of these differences, there are several common and practical concerns among radiation and chemical risk managers. They include 1) the issue of cost for site redevelopment and long-term stewardship, 2) public acceptance and involvement, and 3) the need for flexible risk management framework to address the first two issues. This article attempts to synthesize key differences, opportunities for harmonization, and challenges ahead.

We examined the association of apolipoprotein E (ApoE) genotype and the risk of early-onset Alzheimer's disease (AD) in 209 white early-onset sporadic cases (43% male) and 303 white controls (48% male) of similar age distribution. The risk of AD was significantly increased, relative to the 3/3 genotype, in people with the 4/4, 3/4, and 2/4 genotypes, controlling for age at time of examination and sex. The 2/3 genotype reduced slightly the risk of AD, although the effect was not statistically significant. We conclude, contrary to some previous reports, that the ApoE epsilon2 allele does not increase the risk of early-onset sporadic AD.

Recent reports have shown an association between an intronic polymorphism of the presenilin-1 (PSEN1) gene and late-onset (age at onset > 65) familial and sporadic (no family history) Alzheimer disease (AD). The reported association was independent of the effect of the only previously identified gene associated with late-onset AD, APOE. Blood samples were obtained from members of 122 multiplex AD families, 42 unrelated cases of AD with positive family histories of dementia, 456 sporadic cases of AD, and 317 controls of similar ages at examination to the cases. These samples were genotyped for an intronic polymorphism of the PSEN1 gene, located 3' to exon 8, and the data analyzed for evidence of association or linkage. The samples were also genotyped for APOE and the data analyzed to see if the association or linkage changed when controlling for APOE genotype. There was no statistically significant increase (at alpha = .01) in allele 1 (199 bp) or genotype 1/1 in the sporadic AD cases, or in a random sample of one affected from each multiplex family, compared to controls. When examining the effect of the PSEN1 polymorphism while controlling for APOE genotype, APOE genotype was strongly associated with AD, but the PSEN1 polymorphism genotype was not. Model-trait dependent (lod score) and independent (Sim1BD) methods detected no evidence of linkage between PSEN1 and AD. In this independent dataset, the previously reported association between the intronic PSEN1 polymorphism and AD cannot be confirmed, and the conclusion that PSEN1 is a major susceptibility gene for late-onset AD is not supported.

Alzheimer's disease (AD) is the most common mid to late age-of-onset neurodegenerative disorder. AD has a strong and complex genetic etiology, and multiple genes, acting independently and/or interacting, likely affect the risk of developing AD. Several genes involved with AD already have been described, but only the APOE gene on chromosome 19q has been shown to affect the risk of the most common form of AD, occurring with onset over the age of 65. Because a substantial portion of late-onset AD is not explained by APOE, other genes affecting late-onset AD likely occur. These could act either independently or perhaps interact with APOE. alpha 1-Antichymotrypsin (ACT) is a major component of the amyloid plaques found in the brains of AD patients and may play a role in the pathophysiology of AD. It has been proposed that a specific polymorphism within the ACT gene interacts with APOE to increase the risk of developing AD. Our results do not confirm this finding.

Alzheimer disease (AD) is the most common neurodegenerative disorder for individuals over the age of 40. AD has a complex etiology, and it is likely that multiple genes, acting independently and/or interacting, affect the risk of developing AD. Several genes involved with AD have been described already, but only the APOE gene on chromosome 19q has been shown to affect the risk of the common late onset form of AD. alpha1-Antichymotrypsin (AACT) is a major component of the amyloid plaques found in the brains of AD patients, and an allele in its gene has been proposed to increase the risk of developing AD when also associated with the APOE-4 allele. We have examined the role of this AACT polymorphism in a large set of families and sporadic cases, and do not see any effect, either alone or in combination with the APOE-4 allele.

The apolipoprotein E (APOE) epsilon 4 allele carries an increased risk of a patient developing Alzheimer's disease (AD) while the epsilon 2 allele carries a decreased risk. We compared survival from the onset of AD in subjects with different numbers of epsilon 4 alleles and evaluated changes in genotypic frequencies with age. Two subject groups were investigated: unrelated AD case and control subjects, and affected and unaffected members from 74 multiplex AD families. In both subject groups, survival from onset decreased with increasing onset age, was longer in women, and was unrelated to epsilon 4 gene dose. The epsilon 2/epsilon 3 genotype became more common with age (p = 0.004). The epsilon 4 allele decreased in frequency with age in all patient groups but, unexpectedly, remained unchanged in control subjects. We conclude that the progression of AD is not strongly related to epsilon 4 gene dose, that the higher prevalence of AD in women may involve the longer survival of affected women, and that AD and death are competing risks involving APOE that change over time.

An increased frequency of the apolipoprotein E type 4 allele (APOE-4) has previously been associated with both late-onset sporadic and late-onset familial Alzheimer disease (AD) [Strittmatter et al. (1993) Proc Natl Acad Sci USA 90:1977-1981; Saunders et al. (1993a) Neurology 43:1467-1472]. To further investigate this association we genotyped affected individuals from 92 separate AD pedigrees including both early- and late-onset cases. An increased frequency of the APOE-4 allele was found only among the late-onset cases, both familial and sporadic, confirming the earlier reports. In addition, age at onset was significantly decreased in the APOE-4 homozygotes (in late onset families) compared to either APOE-4 heterozygotes or individuals not carrying an APOE-4 allele. We also observed a significantly decreased frequency of the APOE-2 allele in both the early- and late-onset familial cases. These results strengthen the argument for a direct role of APOE in susceptibility to AD.

Paired and group presentation methods of preference testing were compared with eight learners with severe-profound developmental disabilities. Each presentation method was also compared with staff rankings of learners' preferences. Similar preferences were identified with both presentation methods. Although the paired presentation took more time to administer, it elicited more consistent preference information than the group presentation. Staff preference rankings were not highly correlated with either the group or paired presentation. However, items identified as most preferred by staff and by both presentation methods were similar.

Gene dosage of the apolipoprotein E (APOE) epsilon 4 allele is a major risk factor for familial Alzheimer disease (AD) of late onset (after age 60). Here we studied a large series of 115 AD case subjects and 243 controls as well as 150 affected and 197 unaffected members of 66 AD families. Our data demonstrate a protective effect of the epsilon 2 allele, in addition to the dose effect of the epsilon 4 allele in sporadic AD. Although a substantial proportion (65%) of AD is attributable to the presence of epsilon 4 alleles, risk of AD is lowest in subjects with the epsilon 2/epsilon 3 genotype, with an additional 23% of AD attributable to the absence of an epsilon 2 allele. The opposite actions of the epsilon 2 and epsilon 4 alleles further support the direct involvement of APOE in the pathogenesis of AD.

We have generated an 18-interval contiguous genetic linkage map of human chromosome 4 spanning the entire short arm and proximal long arm. Fifty-seven polymorphisms, representing 42 loci, were analyzed in the Venezuelan reference pedigree. The markers included seven genes (ADRA2C, ALB, GABRB1, GC, HOX7, IDUA, QDPR), one pseudogene (RAF1P1), and 34 anonymous DNA loci. Four loci were represented by microsatellite polymorphisms and one (GC) was expressed as a protein polymorphism. The remainder were genotyped based on restriction fragment length polymorphism. The sex-averaged map covered 123 cM. Significant differences in sex-specific rates of recombination were observed only in the pericentromeric and proximal long arm regions, but these contributed to different overall map lengths of 115 cM in males and 138 cM in females. This map provides 19 reference points along chromosome 4 that will be particularly useful in anchoring and seeding physical mapping studies and in aiding in disease studies.

This investigation compared the transparency of 11 different types of symbols representing objects with 40 nonspeaking subjects who experienced various degrees of intellectual disability. The subjects included a number of individuals with physical impairments or autism in addition to mild, moderate, or severe mental retardation. The symbol sets included: nonidentical objects, miniature objects, identical colored photographs, nonidentical colored photographs, black-and-white photographs, Picture Communication Symbols (PCS), Picsyms, Rebus, Self-Talk, Blissymbols, and written words. Statistical analyses indicated that real objects were more readily recognized than were any of the symbol sets and that Blissymbols and written words were more difficult than were any of the other sets. In addition, the results suggest the existence of a hierarchy of difficulty at the object (noun) level for the symbol sets assessed. The results are discussed in terms of their implications for selecting an initial symbol set for nonspeaking individuals. In addition, some suggestions for using the assessment protocols in clinical practice are presented, along with future research implications.