Time is an essential feature of most decisions, because the reward earned from decisions frequently depends on the temporal statistics of the environment (e.g., on whether decisions must be made under deadlines). Accordingly, evolution appears to have favored a mechanism that predicts intervals in the seconds to minutes range with high accuracy on average, but significant variability from trial to trial. Importantly, the subjective sense of time that results is sufficiently imprecise that maximizing rewards in decision-making can require substantial behavioral adjustments (e.g., accumulating less evidence for a decision in order to beat a deadline). Reward maximization in many daily decisions therefore requires optimal temporal risk assessment. Here, we review the temporal decision-making literature, conduct secondary analyses of relevant published datasets, and analyze the results of a new experiment. The paper is organized in three parts. In the first part, we review literature and analyze existing data suggesting that animals take account of their inherent behavioral variability (their "endogenous timing uncertainty") in temporal decision-making. In the second part, we review literature that quantitatively demonstrates nearly optimal temporal risk assessment with sub-second and supra-second intervals using perceptual tasks (with humans and mice) and motor timing tasks (with humans). We supplement this section with original research that tested human and rat performance on a task that requires finding the optimal balance between two time-dependent quantities for reward maximization. This optimal balance in turn depends on the level of timing uncertainty. Corroborating the reviewed literature, humans and rats exhibited nearly optimal temporal risk assessment in this task. In the third section, we discuss the role of timing uncertainty in reward maximization in two-choice perceptual decision-making tasks and review literature that implicates timing uncertainty as an important factor in performance quality. Together, these studies strongly support the hypothesis that animals take normative account of their endogenous timing uncertainty. By incorporating the psychophysics of interval timing into the study of reward maximization, our approach bridges empirical and theoretical gaps between the interval timing and decision-making literatures.

SCORE, OST and ORAI risk assessment tools could reduce the cost burden of BMD tests by selecting the high risk patients to osteoporosis. In this study we compared the ability of these risk assessment measures to assess probability of the osteoporosis among post-menopausal women.

Venous thromboembolism (VTE) is the most common preventable cause of hospitalization-associated mortality. In the absence of optimal prophylaxis and depending on the type of surgery and patient-related factors, the risk of developing VTE increases by 10% to 50%. We aimed to assess VTE risk and thromboprophylaxis among surgical patients hospitalized at surgical wards of Tikur Anbessa Specialized Hospital (TASH). Addis Ababa, Ethiopia.

Assessing the pandemic risk posed by specific non-human influenza A viruses is an important goal in public health research. As influenza virus genome sequencing becomes cheaper, faster, and more readily available, the ability to predict pandemic potential from sequence data could transform pandemic influenza risk assessment capabilities. However, the complexities of the relationships between virus genotype and phenotype make such predictions extremely difficult. The integration of experimental work, computational tool development, and analysis of evolutionary pathways, together with refinements to influenza surveillance, has the potential to transform our ability to assess the risks posed to humans by non-human influenza viruses and lead to improved pandemic preparedness and response.

Early detection and intervention with young people at clinical high risk (CHR) for psychosis is critical for prevention efforts focused on altering the trajectory of psychosis. Early CHR research largely focused on validating clinical interviews for detecting at-risk individuals; however, this approach has limitations related to: (1) specificity (i.e., only 20% of CHR individuals convert to psychosis) and (2) the expertise and training needed to administer these interviews is limited. The purpose of our study is to develop the computerized assessment of psychosis risk (CAPR) battery, consisting of behavioral tasks that require minimal training to administer, can be administered online, and are tied to the neurobiological systems and computational mechanisms implicated in psychosis. The aims of our study are as follows: (1A) to develop a psychosis-risk calculator through the application of machine learning (ML) methods to the measures from the CAPR battery, (1B) evaluate group differences on the risk calculator score and test the hypothesis that the risk calculator score of the CHR group will differ from help-seeking and healthy controls, (1C) evaluate how baseline CAPR battery performance relates to symptomatic outcome two years later (i.e., conversion and symptomatic worsening). These aims will be explored in 500 CHR participants, 500 help-seeking individuals, and 500 healthy controls across the study sites. This project will provide a next-generation CHR battery, tied to illness mechanisms and powered by cutting-edge computational methods that can be used to facilitate the earliest possible detection of psychosis risk.

Genetics plays an important role in venous thromboembolism (VTE). Factor V Leiden (FVL or rs6025) and prothrombin gene G20210A (PT or rs1799963) are the genetic variants currently tested for VTE risk assessment. We hypothesized that primary VTE risk assessment can be improved by using genetic risk scores with more genetic markers than just FVL-rs6025 and prothrombin gene PT-rs1799963. To this end, we have designed a new genetic risk score called Thrombo inCode (TiC).

The field of environmental public health is at an important crossroad. Our current biomonitoring efforts document widespread exposure to a host of chemicals for which toxicity information is lacking. At the same time, advances in the fields of genomics, proteomics, metabolomics, genetics and epigenetics are yielding volumes of data at a rapid pace. Our ability to detect chemicals in biological and environmental media has far outpaced our ability to interpret their health relevance, and as a result, the environmental risk paradigm, in its current state, is antiquated and ill-equipped to make the best use of these new data. In light of new scientific developments and the pressing need to characterize the public health burdens of chemicals, it is imperative to reinvigorate the use of environmental epidemiology in chemical risk assessment. Two case studies of chemical assessments from the Environmental Protection Agency Integrated Risk Information System database are presented to illustrate opportunities where epidemiologic data could have been used in place of experimental animal data in dose-response assessment, or where different approaches, techniques, or studies could have been employed to better utilize existing epidemiologic evidence. Based on the case studies and what can be learned from recent scientific advances and improved approaches to utilizing human data for dose-response estimation, recommendations are provided for the disciplines of epidemiology and risk assessment for enhancing the role of epidemiologic data in hazard identification and dose-response assessment.

EFSA was asked to deliver a scientific opinion on the risks to public health related to the presence of aflatoxins in food. The risk assessment was confined to aflatoxin B1 (AFB1), AFB2, AFG1, AFG2 and AFM1. More than 200,000 analytical results on the occurrence of aflatoxins were used in the evaluation. Grains and grain-based products made the largest contribution to the mean chronic dietary exposure to AFB1 in all age classes, while 'liquid milk' and 'fermented milk products' were the main contributors to the AFM1 mean exposure. Aflatoxins are genotoxic and AFB1 can cause hepatocellular carcinomas (HCCs) in humans. The CONTAM Panel selected a benchmark dose lower confidence limit (BMDL) for a benchmark response of 10% of 0.4 μg/kg body weight (bw) per day for the incidence of HCC in male rats following AFB1 exposure to be used in a margin of exposure (MOE) approach. The calculation of a BMDL from the human data was not appropriate; instead, the cancer potencies estimated by the Joint FAO/WHO Expert Committee on Food Additives in 2016 were used. For AFM1, a potency factor of 0.1 relative to AFB1 was used. For AFG1, AFB2 and AFG2, the in vivo data are not sufficient to derive potency factors and equal potency to AFB1 was assumed as in previous assessments. MOE values for AFB1 exposure ranged from 5,000 to 29 and for AFM1 from 100,000 to 508. The calculated MOEs are below 10,000 for AFB1 and also for AFM1 where some surveys, particularly for the younger age groups, have an MOE below 10,000. This raises a health concern. The estimated cancer risks in humans following exposure to AFB1 and AFM1 are in-line with the conclusion drawn from the MOEs. The conclusions also apply to the combined exposure to all five aflatoxins.

Neurobehavioral tests are being increasingly used in human risk assessment and there is a strong need for guidance. The field of neurobehavioral toxicology has evolved from research which initially focused on using traditional neuropsychological tests to identify "abnormal cases" to include methods used to detect sub-clinical deficits, to further incorporate the use of neurosensory assessment, and to expand testing from occupational populations to vulnerable populations including older adults and children. Even as exposures in the workplace are reduced, they have been increasing in the environment and research on exposure has now expanded to cross the entire lifetime. These neurobehavioral methods are applied in research and the findings used for regulatory purposes to develop preventative action for exposed populations. This paper reflects a summary of the talks presented at the Neurobehavioral Testing in Human Risk Assessment symposium presented at the 11th meeting of the International Neurotoxicology Association.

All rigorous primary cardiovascular disease (CVD) prevention guidelines recommend absolute CVD risk scores to identify high- and low-risk patients, but laboratory testing can be impractical in low- and middle-income countries. The purpose of this study was to compare the ranking performance of a simple, non-laboratory-based risk score to laboratory-based scores in various South African populations.

The Next Generation (NexGen) of Risk Assessment effort is a multi-year collaboration among several organizations evaluating new, potentially more efficient molecular, computational, and systems biology approaches to risk assessment. This article summarizes our findings, suggests applications to risk assessment, and identifies strategic research directions.

We investigated the performance of a gastric cancer (GC) risk assessment model in combination with single-nucleotide polymorphisms (SNPs) as a polygenic risk score (PRS) in consideration of Helicobacter pylori (H. pylori) infection status. Six SNPs identified from genome-wide association studies and a marginal association with GC in the study population were included in the PRS. Discrimination of the GC risk assessment model, PRS, and the combination of the two (PRS-GCS) were examined regarding incremental risk and the area under the receiver operating characteristic curve (AUC), with grouping according to H. pylori infection status. The GC risk assessment model score showed an association with GC, irrespective of H. pylori infection. Conversely, the PRS exhibited an association only for those with H. pylori infection. The PRS did not discriminate GC in those without H. pylori infection, whereas the GC risk assessment model showed a modest discrimination. Among individuals with H. pylori infection, discrimination by the GC risk assessment model and the PRS were comparable, with the PRS-GCS combination resulting in an increase in the AUC of 3%. In addition, the PRS-GCS classified more patients and fewer controls at the highest score quintile in those with H. pylori infection. Overall, the PRS-GCS improved the identification of a GC-susceptible population of people with H. pylori infection. In those without H. pylori infection, the GC risk assessment model was better at identifying the high-risk group.

The way in which risk communication messages are framed can influence recipients' risk perceptions. Despite this, there is a limited understanding of how framing is responsible for influencing risk perception. One particularly important element may be whether a risk communication message is framed as a completed 'risk assessment' (specifying a magnitude of risk to the public as a function of the exposure level), or as a 'hazard identification' (a statement regarding whether an environmental agent could in principle cause detrimental health effects in humans, without addressing whether such effects may occur in practice). The current study aimed to investigate for the first time whether framing a risk communication message regarding 'mobile phones and health' as a hazard identification or as a risk assessment affects the reader's risk perception. Using an online survey, participants were separated into three groups and shown either an original press release from the International Agency for Research on Cancer regarding mobile phones and cancer (Group 1), or the press release with additional text modules intended to frame the press release as either a risk assessment (Group 2) or a hazard identification (Group 3). The experimental manipulation was successful in that framing the message as a hazard identification reduced the number of people that believed the press release was a risk assessment, whereas framing it as a risk assessment was not able to increase the number of people who thought that it was a risk assessment. However, no differences in risk perception were found between the groups. In an attempt to ascertain the reason for this lack of framing effect on the radiofrequency electromagnetic fields risk perception measures, it was found that pre-existing interpretations of risk and hazard strongly predicted risk perception, regardless of experimental group. Participants who believed that the International Agency for Research on Cancer conducted a hazard identification perceived lower risks and were less convinced that radiofrequency electromagnetic field exposure from mobile phones increases cancer risks. The results of the study demonstrate the importance of understanding the distinction between a hazard identification and a risk assessment, and suggest that radiofrequency electromagnetic field risk communication needs to develop means for empowering the public to differentiate between hazards and risks.

Polygenic risk scores (PRS) allow risk stratification using common single-nucleotide polymorphisms (SNPs), and clinical applications are currently explored for several diseases. This study was undertaken to assess the risk of hip and knee osteoarthritis (OA) using PRS.

Bone health and fracture risk reduction are increasingly recognized as important issues in Parkinson's disease (PD). However, the evidence for fracture risk management in atypical parkinsonism (AP) is less clear. Guidance on management of bone health in PD has recently been published.

A possible way to alleviate the public skepticism toward regulatory science is to increase transparency by making all data and value judgments used in regulatory decision making accessible for public interpretation, ideally early on in the process, and following the concepts of Open Science. This paper discusses the opportunities and challenges in strengthening Open Science initiatives in regulatory environmental risk assessment (ERA). In this discussion paper, we argue that the benefits associated with Open Science in regulatory ERA far outweigh its perceived risks. All stakeholders involved in regulatory ERA (e.g., governmental regulatory authorities, private sector, academia, and nongovernmental organizations), as well as professional organizations like the Society of Environmental Toxicology and Chemistry, can play a key role in supporting the Open Science initiative, by promoting the use of recommended reporting criteria for reliability and relevance of data and tools used in ERA, and by developing a communication strategy for both professionals and nonprofessionals to transparently explain the socioeconomic value judgments and scientific principles underlying regulatory ERA. Integr Environ Assess Manag 2021;17:1229-1242. © 2021 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

The European Commission asked EFSA to update their 2006 opinion on ochratoxin A (OTA) in food. OTA is produced by fungi of the genus Aspergillus and Penicillium and found as a contaminant in various foods. OTA causes kidney toxicity in different animal species and kidney tumours in rodents. OTA is genotoxic both in vitro and in vivo; however, the mechanisms of genotoxicity are unclear. Direct and indirect genotoxic and non-genotoxic modes of action might each contribute to tumour formation. Since recent studies have raised uncertainty regarding the mode of action for kidney carcinogenicity, it is inappropriate to establish a health-based guidance value (HBGV) and a margin of exposure (MOE) approach was applied. For the characterisation of non-neoplastic effects, a BMDL 10 of 4.73 μg/kg body weight (bw) per day was calculated from kidney lesions observed in pigs. For characterisation of neoplastic effects, a BMDL 10 of 14.5 μg/kg bw per day was calculated from kidney tumours seen in rats. The estimation of chronic dietary exposure resulted in mean and 95th percentile levels ranging from 0.6 to 17.8 and from 2.4 to 51.7 ng/kg bw per day, respectively. Median OTA exposures in breastfed infants ranged from 1.7 to 2.6 ng/kg bw per day, 95th percentile exposures from 5.6 to 8.5 ng/kg bw per day in average/high breast milk consuming infants, respectively. Comparison of exposures with the BMDL 10 based on the non-neoplastic endpoint resulted in MOEs of more than 200 in most consumer groups, indicating a low health concern with the exception of MOEs for high consumers in the younger age groups, indicating a possible health concern. When compared with the BMDL 10 based on the neoplastic endpoint, MOEs were lower than 10,000 for almost all exposure scenarios, including breastfed infants. This would indicate a possible health concern if genotoxicity is direct. Uncertainty in this assessment is high and risk may be overestimated.

A report on the Contemporary Concepts in Toxicology workshop 'Use of Genomic Data in Risk Assessment: State of the Art 2001' held by the Society of Toxicology, Washington DC, USA, 7-8 November 2001.

Bees are essential pollinators of many plants in natural ecosystems and agricultural crops alike. In recent years the decline and disappearance of bee species in the wild and the collapse of honey bee colonies have concerned ecologists and apiculturalists, who search for causes and solutions to this problem. Whilst biological factors such as viral diseases, mite and parasite infections are undoubtedly involved, it is also evident that pesticides applied to agricultural crops have a negative impact on bees. Most risk assessments have focused on direct acute exposure of bees to agrochemicals from spray drift. However, the large number of pesticide residues found in pollen and honey demand a thorough evaluation of all residual compounds so as to identify those of highest risk to bees. Using data from recent residue surveys and toxicity of pesticides to honey and bumble bees, a comprehensive evaluation of risks under current exposure conditions is presented here. Standard risk assessments are complemented with new approaches that take into account time-cumulative effects over time, especially with dietary exposures. Whilst overall risks appear to be low, our analysis indicates that residues of pyrethroid and neonicotinoid insecticides pose the highest risk by contact exposure of bees with contaminated pollen. However, the synergism of ergosterol inhibiting fungicides with those two classes of insecticides results in much higher risks in spite of the low prevalence of their combined residues. Risks by ingestion of contaminated pollen and honey are of some concern for systemic insecticides, particularly imidacloprid and thiamethoxam, chlorpyrifos and the mixtures of cyhalothrin and ergosterol inhibiting fungicides. More attention should be paid to specific residue mixtures that may result in synergistic toxicity to bees.

Phenylketonuria (PKU) is a rare congenital disorder caused by decreased metabolism of phenylalanine determining cerebral impairments. If untreated, PKU might lead to intellectual disability, seizures and behavioral disorders. The aim of this study is to provide a characterization of the psychopathological profile of a pediatric population diagnosed with PKU at newborn screening.