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In France, patients' right to take part in decisions regarding their health has been recognized by law since 2002. This legal recognition was the outcome of a long-standing call to allow all individuals to be "actors in their own health" and to co-develop their care pathway with the professionals involved. In practice, care pathways simultaneously intertwine both standardization and personalization dynamics, which involve different forms of professional-patient interaction. This article analyses the links between the organizational variables of care pathways, and the ways in which patients are involved in the management of their own pathway. To date, these links have received little attention in the management science and health literatures. We draw on material from a case study carried out in 2 French territories, combining the analysis of patient pathways with interviews conducted with professionals and carers. Building on this analysis, we propose a typology of patient profiles which distinguishes between their different forms of involvement in the development of their care pathway, based on its organizational characteristics., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Objectives: Current treatments for benign vocal lesions consist mainly voice therapy and phonomicrosurgery. However, these options are not always suitable for professional voice users because of their tight performance schedule and limited time for voice rest. This study investigated vocal fold steroid injection (VFSI) as an alternative treatment., Study Design: Matched case series., Methods: We retrospectively enrolled 28 professional voice users (i.e., singers, actors and news anchors) who received VFSI for vocal nodules and polyps in an office setting of a tertiary teaching hospital. Outcomes were evaluated using videolaryngostroboscopy (VLS), the 10-item Voice Handicap Index (VHI-10), maximum phonation time, and acoustic and perceptual analyses before and 1 month after VFSI. Study results were compared with 56 patients of nonprofessional voice users (i.e., routine or high occupational vocal demands), matched in a 1:2 ratio by age, sex, and treatment date., Results: After VFSI, VLS revealed substantial lesion resolution in 82% professional voice users. One professional voice user developed a self-limited vocal fold hematoma after VFSI. VHI-10 scores in the professional group decreased from 21 to 14 points, compared with 23 to 16 points in the non-professional group, demonstrating a significant within-group effect (P < 0.01, GEE) and a nonsignificant between-group effect (P = 0.86). Other outcomes also improved significantly after VFSI (P < 0.05), without significant differences between the two groups., Conclusion: VFSI can be an effective and safe alternative treatment for professional voice users with benign vocal lesions., (Copyright © 2021 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Mild traumatic brain injury (mTBI) accounts for approximately 80% of all TBI cases and is a growing source of morbidity and mortality worldwide. To improve the management of children and adults with mTBI, a series of candidate biomarkers have been investigated in recent years. In this context, the measurement of blood biomarkers in the acute phase after a traumatic event helps reduce unnecessary CT scans and hospitalizations. In athletes, improved management of sports-related concussions is also sought to ensure athletes' safety. S100B protein has emerged as the most widely studied and used biomarker for clinical decision making in patients with mTBI. In addition to its use as a diagnostic biomarker, S100B plays an active role in the molecular pathogenic processes accompanying acute brain injury. This review describes S100B protein as a diagnostic tool as well as a potential therapeutic target in patients with mTBI.

Introduction: The voice production of actors is complex and can be assessed by different professionals. The objective of this study was to measure actor's global vocal performance (GVP) based on overall voice quality (OVQ) and overall severity (OS), by consensus auditory-perceptual evaluation of voice (CAPE-V), and to investigate the possible correlation between these two analyses in actors without self-reported vocal complaints., Methods: A total of 39 actors participated in this study, including 20 men and 19 women. Their ages ranged from 18 to 53 years (mean of 33.3 years), with a mean duration of eight years of professional experience. The referred actors were asked to perform predefined CAPE-V tasks and provide one voice sample in which they read a poem at normal loudness; all tasks were recorded. A professional speech-language therapist evaluated the OS based on CAPE-V vocal tasks; scores up to 35.5 mm represented normal parameters, while those from 35.6 to 50.5 mm represented mild deviation, 50.6 to 90.5 mm indicated moderate deviation, and 90.6 to 100 mm indicated severe deviation. A theater director and another speech-language therapist classified the voice samples using the OVQ scale. The OVQ was measured using a 200-mm visual analogue scale. The calculation of terciles allowed the division into three groups regarding the GVP: lowest score group; intermediate score group; and highest score group. The scores of both analyses were compared by sex and groups. Lastly, a correlation analysis was performed between the two analyses for the total sample., Results: There was a significant difference among the three groups and a mild vocal deviation in the lowest score group. In addition, an inversely proportional correlation was observed between GVP and OS. No sex-related differences were observed in the scores for either analyses., Conclusion: The actors without self-reported voice complaints presented differences on GVP scores and their distribution was independent of sex and length of professional experience. Vocal deviation, although mild, on average was greater in actors who had the lowest scores in GVP, with an inversely proportional correlation between these two parameters., (Copyright © 2020 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Clinical relevance : The ability to articulate clinical findings to patients through effective communication is a key skill in all health-care professions. Background : Unannounced standardised patients (SPs) are successful in measuring quality of clinical care provided by qualified optometrists but have not been used in optometry training. Final-year undergraduate optometry students examine members of the public during primary care clinics observed by visiting clinical tutors (VCTs) who provide individualised feedback, highlighting areas for improvement. This pilot study investigates whether unannounced SPs can be used as an additional resource providing enhanced feedback on communication skills in undergraduate optometry education. Methods : Two SPs received intensive training on reporting on students eye examinations and communication skills through completion of pre-designed checklists for each patient encounter. Each SP presented 16 times as an unannounced patient for routine eye examinations. SPs' comments on communication skills of 32 students during 32 examinations was compared to feedback from 10 VCTs. SPs' performance was monitored to ensure consistency. Evaluation of differences in quality and quantity of feedback provided by SPs and VCTs was performed using thematic analysis and chi-squared tests. Student feedback on the use of SPs was obtained on completion of the study. Results : Qualitative thematic analysis revealed six overarching themes emerging from 64 sets of feedback. SPs gave significantly more feedback, both positive comments and comments with recommendations, than VCTs for the (a) total number of comments for each theme (p = 0.0000) and (b) detail and depth of these comments. Students reported that SPs commented on aspects of communication (e.g., establishing rapport and body language) not noted by VCTs. Conclusions : Unannounced SPs can provide enhanced feedback on communication skills to final-year undergraduate optometry students. Students greatly valued VCTs feedback; however, they felt SPs commented on elements of communication not noted by VCTs.

Objectives: This study described voice use and lifestyle information about student actors and assessed whether different information is reported at study intake compared to data extracted from a 3-week voice Log., Methods: Twenty-five student actors estimated 14 voice and life style parameters at the start of the study. These included daily speaking time, performance time, vocal warm-up, and cool-down time; intake of water, caffeine, and alcohol; perceived voice effort (speaking and performance), among other items. The same parameters were tracked by the actor for 21 consecutive days. Nonparametric statistical comparisons of the estimates at intake to the median estimate from 21 days were applied., Results: Student actors reported frequent yelling (48%), frustration, anxiety, and depression about their voice (52%, 48%, and 16%), issues with breath support (56%), vocal fatigue (36%), and mild-moderate effort in the speaking (24%) and performance voice (70%). Estimates at study intake statistically overestimated daily speaking, performance, and vocal warm-up time compared to the 3-week Log. Intake reporting underestimated perceived effort in the speaking voice. Intake reporting of vocal fatigue and voice quality did not closely correspond to the Log data., Conclusion: Student actors reported a number of voice use and lifestyle behaviors that may increase their risk for voice problems. Additionally, the method of soliciting the history altered the information reported by the students for several parameters. The findings highlight the need to develop history gathering or other methods that optimize accuracy and reliability of the information sought., (Copyright © 2019 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Suboptimal breastfeeding practices are driven by multiple factors. Thus, a multi-sectoral approach is necessary to design and implement appropriate policies and programs that protect, promote, and support breastfeeding., Methods: This study used Net-Map, an interactive social network interviewing and mapping technique, to: a) identify key institutional actors involved in breastfeeding policy/programs in Ghana, b) identify and describe links between actors (i.e., command, dissemination, funding, and technical assistance (TA)), and c) document actors influence to initiate or modify breastfeeding policy/programs. Ten experts were purposively selected from relevant institutions and were individually interviewed. Interview data was analysed using social networking mapping software, Gephi (version 0.9.2)., Results: Forty-six unique actors were identified across six actor categories (government, United Nations agencies, civil society, academia, media, others), with one-third being from government agencies. Dissemination and TA links accounted for two-thirds of the identified links between actors (85/261 links for dissemination; 85/261 for TA). Command links were mainly limited to government agencies, while other link types were observed across all actor groups. Ghana Health Service (GHS) had the greatest in-degree centrality for TA and funding links, primarily from United Nations Children's Fund (UNICEF) and development partners. The World Health Organization, UNICEF, Ministry of Health, and GHS had the highest weighted average relative influence scores., Conclusions: Although diverse actors are involved in breastfeeding policy and programming in Ghana, GHS plays a central role. United Nations and donor agencies are crucial supporters of GHS providing breastfeeding technical and financial assistance in Ghana.

Behavior requires an actor. Two experiments using complex conditional action discriminations examined whether pigeons privilege information related to the digital actor who is engaged in behavior. In Experiment 1, each of two video displays contained a digital model, one an actor engaged in one of two behaviors (Indian dance or martial arts) and one a neutrally posed bystander. To correctly classify the display, the pigeons needed to conditionally process the action in conjunction with distinctive physical features of the actor or the bystander. Four actor-conditional pigeons learned to correctly discriminate the actions based on the identity of the actors, whereas four bystander-conditional birds failed to learn. Experiment 2 established that this failure was not due to the latter group's inability to spatially integrate information across the distance between the two models. Potentially, the colocalization of the relevant model identity and the action was critical due to a fundamental configural or integral representation of these properties. These findings contribute to our understanding of the evolution of action recognition, the recognition of social behavior, and forms of observational learning by animals.

Actors must realistically portray imagined characters in imaginary circumstances by "becoming" their characters. What is it that allows them to do this? We suggest that acting is related to dissociation, a trait typically related to psychopathology. We measured dissociation in 53 conservatory acting students before and after six months of training, using the Dissociative Experiences Scale-II (DES-II). Although no significant changes occurred over time, acting students scored significantly higher than the general population on the DES-II. These scores were driven by just one of the subscales - absorption and imaginative involvement. We argue here that this subscale measures a trait central to the creative process. Furthermore, although the DES-II was designed to measure psychopathology, we found that it is also related to flow (a positive experience). Certain flow dimensions were predictive of dissociation and of its absorption and imaginative involvement subscale. We conclude that total DES-II scores may not necessarily indicate psychopathology in actors. At the very least, these results suggest that clinicians should take extra precaution when diagnosing dissociation in actors using the DES-II.

Action is a key channel for interacting with the outer world. As such, the ability to monitor actions and their consequences - regardless as to whether they are self-generated or other-generated - is of crucial importance for adaptive behavior. The medial frontal cortex (MFC) has long been studied as a critical node for performance monitoring in nonsocial contexts. Accumulating evidence suggests that the MFC is involved in a wide range of functions necessary for one's own performance monitoring, including error detection, and monitoring and resolving response conflicts. Recent studies, however, have also pointed to the importance of the MFC in performance monitoring under social conditions, ranging from monitoring and understanding others' actions to reading others' mental states, such as their beliefs and intentions (i.e., mentalizing). Here we review the functional roles of the MFC and related neural networks in performance monitoring in both nonsocial and social contexts, with an emphasis on the emerging field of a social systems neuroscience approach using macaque monkeys as a model system. Future work should determine the way in which the MFC exerts its monitoring function via interactions with other brain regions, such as the superior temporal sulcus in the mentalizing system and the ventral premotor cortex in the mirror system., (Copyright © 2018. Published by Elsevier B.V.)

Individuals often fail to accurately predict others' decisions in a risky environment. In this paper, we investigate the characteristics and causes of this prediction discrepancy. Participants completed a risky decision-making task mixed with different domains (gain vs. loss) and probabilities (small vs. large), with some participants making decisions for themselves (the actor) and the others predicting the actors' decisions (the predictor). The results demonstrated a prediction discrepancy: predictions were more risk-averse than the actual decisions over small-probability gains and more risk-seeking over large-probability gains, while these patterns were reversed in the loss domain. Reported and predicted levels of emotional stimulation revealed a pattern that is consistent with the notion of risk-as-feelings and empathy gaps. Mediation analysis provided strong evidence that such prediction discrepancy is driven mainly by the predictor's underestimate of the intensity (not the impact) of the actor's emotional state.

Background . There are numerous approaches to simulating a patient encounter in pharmacy education. However, little direct comparison between these approaches has been undertaken. Our objective was to investigate student experiences, satisfaction, and feedback preferences between three scenario simulation modalities (paper-, actor-, and computer-based). Methods . We conducted a mixed methods study with randomized cross-over of simulation modalities on final-year Australian graduate-entry Master of Pharmacy students. Participants completed case-based scenarios within each of three simulation modalities, with feedback provided at the completion of each scenario in a format corresponding to each simulation modality. A post-simulation questionnaire collected qualitative and quantitative responses pertaining to participant satisfaction, experiences, and feedback preferences. Results . Participants reported similar levels satisfaction across all three modalities. However, each modality resulted in unique positive and negative experiences, such as student disengagement with paper-based scenarios. Conclusion . Importantly, the themes of guidance and opportunity for peer discussion underlie the best forms of feedback for students. The provision of feedback following simulation should be carefully considered and delivered, with all three simulation modalities producing both positive and negative experiences in regard to their feedback format.

Specific emotions, especially guilt, are considered to facilitate children's prosocial behavior. The current study differentiated moral stories with a helping theme in terms of the valence and source of emotions and aimed to clarify the effect of these stories on preschoolers' helping intentions and behavior. A total of 322 preschoolers between 4 and 6 years old were randomly assigned to four experimental groups and one control group. A specific type of moral story was presented to each of the experimental groups, whereas a nonmoral story was presented to the control group. The preschoolers were also asked to answer relevant questions to examine their story comprehension. The preschoolers' donating intentions and behavior were then measured. The results showed that all the experimental groups expressed more donating intentions than the control group. However, only the group that read the moral story emphasizing the actor's negative emotions toward his nonhelping behavior displayed more donating behavior than the control group. Therefore, the current study reveals that various moral stories dealing with a helping theme can facilitate helping intentions among preschoolers and that only certain stories can promote their helping behavior. Thus, it indicates the specificity of moral stories that facilitate prosocial behavior in terms of the valence and source of emotions in those stories., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Acute states of agitation (ASAs) are frequent in daily medical practice. However, training on real ASAs raises technical and ethical issues, whereas lecture-based teaching hardly addresses some educational objectives, e.g., improving relational skills and team-based coordination. Simulation-based medical education (SBME) is a promising medium to train students on managing ASAs. We have recently implemented a role-playing training module on ASAs. In this scenario, four to five students play the role of the staff, while a trained professional actor plays the agitated patient. A subsequent standardized debriefing is conducted by a senior psychiatrist. A first wave of 219 students participated in a one-session training of this ASA module in June 2015. They completed pre-session and post-session questionnaires aiming to collect "proof-of-concept" data., Methods: The pre-session questionnaire investigated: previous experience of ASA among students during their clinical training; previous participation in a role-playing SBME; and perceived knowledge of the good practice rules for managing ASAs. The post-session questionnaire investigated among the students if: they thought having been able to appropriately manage the simulated ASA; they found the SBME medium more fitted for training than real situations; they found that the SBME session faithfully reproduced a real ASA; and the session was found useful for transmitting the skills on correct management of ASA. The average level of stress induced by the training was assessed using a numerical rating scale (0-10)., Results: Two hundred and six of the 219 students completed the pre-session questionnaire (63% females; response rate 96.7%). A hundred and thirty four students played the scenario and completed the post-session questionnaire (65.7% females; response rate 100%). 38.3% of the responders reported having previously experienced a situation of ASA in their practice, and 31.1% deemed to know the good practices rules for managing an ASA. In post-session, 29.9% of the participants considered that they appropriately managed the ASA, 79.9% deemed that the role-playing session faithfully reproduced a real ASA, and 97% deemed that this SBME was more fitted and useful than a real clinical situation to improve their medical skills. Bivariate analyses revealed that the post-session responses and level of stress were not influenced by previous experience on ASA, previous participation in a SBME role-playing session, or thinking to know the rules for managing ASAs., Conclusion: SBME role-playing training appears a promising, realistic, and well-accepted method for teaching the management of ASA., (Copyright © 2017 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Background: Despite concerted effort from government and partners, Nepal continues to have a high burden of under nutrition among children. Identifying opportunities to strengthen policy support for infant and young child feeding (IYCF) is a key component to improve child survival, growth and development. This study aims to explore policy support for IYCF and to identify the influential stakeholders for IYCF for effective future policy development and programmatic action., Methods: Policies relevant to IYCF were identified through web searches and direct approaches to relevant government ministries. Policy content was analysed based on four key domains focussed on mothers, using a qualitative synthesis approach. Three group interviews were conducted using the participatory tool "Net-Map", to identify the influential stakeholders in IYCF policy and programming processes., Results: Twenty-six relevant policy documents were analysed for content relating to IYCF. General support for IYCF was found in most of the development plans and high-level health sector policies. Most implementation level documents included support for provision of correct information to mothers. Capacity building of frontline workers for IYCN and system strengthening were well supported through sectoral plans and policies. However, gaps were identified regarding maternity protection, support for monitoring and evaluation, and translation of high-level policy directives into implementation level guidelines, resulting in a lack of clarity over roles and responsibilities. Both government and non-governmental stakeholders, particularly donors, emerged as influential drivers of IYCF policy decisions in Nepal, through technical assistance and funding. The Nutrition Technical Committee under the Ministry of Health, UNICEF, Suaahara, USAID and WHO were identified as key actors providing technical assistance. Key funding agencies were identified as UNICEF and USAID., Conclusions: This study reveals strong policy support for key dimensions of IYCF, supported by a highly networked stakeholder environment. Opportunities to further strengthen IYCF policy in Nepal include: further support for training of frontline workers and complementary feeding interventions; extending maternity leave provisions; and clarifying roles and responsibilities of actors, particularly non-governmental actors. Engaging technical and funding agencies and developing partnerships with other relevant actors will be crucial for ensuring effective policy translates into effective practice.

The actor nodes are the spine of wireless sensor and actor networks (WSANs) that collaborate to perform a specific task in an unverified and uneven environment. Thus, there is a possibility of high failure rate in such unfriendly scenarios due to several factors such as power consumption of devices, electronic circuit failure, software errors in nodes or physical impairment of the actor nodes and inter-actor connectivity problem. Therefore, it is extremely important to discover the failure of a cut-vertex actor and network-disjoint in order to improve the Quality-of-Service (QoS). In this paper, we propose an Efficient Actor Recovery (EAR) paradigm to guarantee the contention-free traffic-forwarding capacity. The EAR paradigm consists of a Node Monitoring and Critical Node Detection (NMCND) algorithm that monitors the activities of the nodes to determine the critical node. In addition, it replaces the critical node with backup node prior to complete node-failure which helps balancing the network performance. The packets are handled using Network Integration and Message Forwarding (NIMF) algorithm that determines the source of forwarding the packets; either from actor or sensor. This decision-making capability of the algorithm controls the packet forwarding rate to maintain the network for a longer time. Furthermore, for handling the proper routing strategy, Priority-Based Routing for Node Failure Avoidance (PRNFA) algorithm is deployed to decide the priority of the packets to be forwarded based on the significance of information available in the packet. To validate the effectiveness of the proposed EAR paradigm, the proposed algorithms were tested using OMNET++ simulation.

We describe the case of an accomplished actor, whom we term AB, who suffered severe amnesia following a cardiac arrest and hypoxic brain damage, affecting medial temporal and thalamic structures. His performance on standard episodic memory tests, and on measures of retrograde amnesia, including autobiographical memory, was severely impaired. When presented with passages from plays he had not appeared in, AB showed a severe impairment at the first learning trial, but thereafter showed a 'normal' learning curve for this semantically and syntactically complex material. On being presented with passages from plays he had performed in the past, AB did not show any recognition of them whatsoever, as one might expect from his severe episodic memory impairment. However, AB showed a striking benefit (savings score) in relearning passages he had previously performed, compared with new passages, despite not having any autobiographical recall of having performed the relearned passages before. Moreover, although his initial recall performance in learning these passages was impaired compared with healthy control actors of similar age and experience, AB demonstrated the same incremental learning rate on subsequent learning trials of the passages as did the controls. We conclude that, although severely impaired at the first learning trial (on both 'new' and 'old' passages), AB was able to employ his long-established semantic and procedural skills to attempt the task, and that thereafter he showed a 'normal' rate of incremental learning from a lower baseline., (Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.)

Couldn׳t a humble coconut hurt a gardener? At least in the first instance, the brain seems to assume that it should not: we perceive inanimate entities such as coconuts as poor event instigators ("Actors"). Ideally, entities causing a change in another entity should be animate and this assumption not only influences event perception but also carries over to language comprehension. We present three auditory event-related brain potential (ERP) studies on the processing of inanimate and animate subjects and objects in simple transitive sentences in Tamil. ERP responses were measured at the second argument (event participant) in all three studies. Experiment 1 employed all possible animacy combinations of Actors and Undergoers (affected participants) in Actor- and Undergoer-initial verb-final orders. Experiments 2 and 3 employed a fairly novel context design that enabled us to compare ERPs evoked by identical auditory material to differing contextual expectations: Experiment 2 focussed on constructions in which an inanimate Actor acts upon an inanimate Undergoer, whereas Experiment 3 examined whether and how a preceding context modulates the prediction for an ideal Actor. Results showed an N400 effect when the prediction for an ideal (animate) Actor following an Undergoer was not met, thus further supporting the cross-linguistically robust nature of animacy preferences. In addition, though specific contextual cues that are indicative of a forthcoming non-ideal Actor may reduce this negativity in comparison to when such cues are not available, they nevertheless do not nullify it, suggesting that animacy-based predictions are stronger than contextual cues in online language comprehension., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The inference of causality is a crucial cognitive ability and language processing is no exception: recent research suggests that, across different languages, the human language comprehension system attempts to identify the primary causer of the state of affairs described (the "actor") quickly and unambiguously (Bornkessel-Schlesewsky and Schlesewsky, 2009). This identification can take place verb-independently based on certain prominence cues (e.g., case, word order, animacy). Here, we present two experiments demonstrating that actor potential is also encoded at the level of individual nouns (a king is a better actor than a beggar). Experiment 1 collected ratings for 180 German nouns on 12 scales defined by adjective oppositions and deemed relevant for actorhood potential. By means of structural equation modeling, an actor potential (ACT) value was calculated for each noun. Experiment 2, an event-related potential study, embedded nouns from Experiment 1 in verb-final sentences, in which they were either actors or non-actors. N400 amplitude increased with decreasing ACT values and this modulation was larger for highly frequent nouns and for actor versus non-actor nouns. We argue that potency to act is lexically encoded for individual nouns and, since it modulates the N400 even for non-actor participants, it should be viewed as a property that modulates ease of lexical access (akin, for example, to lexical frequency). We conclude that two separate dimensions of actorhood computation are crucial to language comprehension: an experience-based, lexically encoded (bottom-up) representation of actorhood potential, and a prominence-based, computational mechanism for calculating goodness-of-fit to the actor role in a particular (top-down) sentence context.

The screening and careful selection of excipients is a critical step in paediatric formulation development as certain excipients acceptable in adult formulations, may not be appropriate for paediatric use. While there is extensive toxicity data that could help in better understanding and highlighting the gaps in toxicity studies, the data are often scattered around the information sources and saddled with incompatible data types and formats. This paper is the second in a series that presents the update on the Safety and Toxicity of Excipients for Paediatrics ("STEP") database being developed by Eu-US PFIs, and describes the architecture data fields and functions of the database. The STEP database is a user designed resource that compiles the safety and toxicity data of excipients that is scattered over various sources and presents it in one freely accessible source. Currently, in the pilot database data from over 2000 references/10 excipients presenting preclinical, clinical, regulatory information and toxicological reviews, with references and source links. The STEP database allows searching "FOR" excipients and "BY" excipients. This dual nature of the STEP database, in which toxicity and safety information can be searched in both directions, makes it unique from existing sources. If the pilot is successful, the aim is to increase the number of excipients in the existing database so that a database large enough to be of practical research use will be available. It is anticipated that this source will prove to be a useful platform for data management and data exchange of excipient safety information., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Response to environmental chemicals can vary widely among individuals and between population groups. In human health risk assessment, data on susceptibility can be utilized by deriving risk levels based on a study of a susceptible population and/or an uncertainty factor may be applied to account for the lack of information about susceptibility. Defining genetic susceptibility in response to environmental chemicals across human populations is an area of interest in the NAS' new paradigm of toxicity pathway-based risk assessment. Data from high-throughput/high content (HT/HC), including -omics (e.g., genomics, transcriptomics, proteomics, metabolomics) technologies, have been integral to the identification and characterization of drug target and disease loci, and have been successfully utilized to inform the mechanism of action for numerous environmental chemicals. Large-scale population genotyping studies may help to characterize levels of variability across human populations at identified target loci implicated in response to environmental chemicals. By combining mechanistic data for a given environmental chemical with next generation sequencing data that provides human population variation information, one can begin to characterize differential susceptibility due to genetic variability to environmental chemicals within and across genetically heterogeneous human populations. The integration of such data sources will be informative to human health risk assessment., (Copyright © 2011. Published by Elsevier Inc.)

Computational toxicology combines data from high-throughput test methods, chemical structure analyses and other biological domains (e.g., genes, proteins, cells, tissues) with the goals of predicting and understanding the underlying mechanistic causes of chemical toxicity and for predicting toxicity of new chemicals and products. A key feature of such approaches is their reliance on knowledge extracted from large collections of data and data sets in computable formats. The U.S. Environmental Protection Agency (EPA) has developed a large data resource called ACToR (Aggregated Computational Toxicology Resource) to support these data-intensive efforts. ACToR comprises four main repositories: core ACToR (chemical identifiers and structures, and summary data on hazard, exposure, use, and other domains), ToxRefDB (Toxicity Reference Database, a compilation of detailed in vivo toxicity data from guideline studies), ExpoCastDB (detailed human exposure data from observational studies of selected chemicals), and ToxCastDB (data from high-throughput screening programs, including links to underlying biological information related to genes and pathways). The EPA DSSTox (Distributed Structure-Searchable Toxicity) program provides expert-reviewed chemical structures and associated information for these and other high-interest public inventories. Overall, the ACToR system contains information on about 400,000 chemicals from 1100 different sources. The entire system is built using open source tools and is freely available to download. This review describes the organization of the data repository and provides selected examples of use cases.

Objective: Thousands of chemicals are in common use, but only a portion of them have undergone significant toxicologic evaluation, leading to the need to prioritize the remainder for targeted testing. To address this issue, the U.S. Environmental Protection Agency (EPA) and other organizations are developing chemical screening and prioritization programs. As part of these efforts, it is important to catalog, from widely dispersed sources, the toxicology information that is available. The main objective of this analysis is to define a list of environmental chemicals that are candidates for the U.S. EPA screening and prioritization process, and to catalog the available toxicology information., Data Sources: We are developing ACToR (Aggregated Computational Toxicology Resource), which combines information for hundreds of thousands of chemicals from > 200 public sources, including the U.S. EPA, National Institutes of Health, Food and Drug Administration, corresponding agencies in Canada, Europe, and Japan, and academic sources., Data Extraction: ACToR contains chemical structure information; physical-chemical properties; in vitro assay data; tabular in vivo data; summary toxicology calls (e.g., a statement that a chemical is considered to be a human carcinogen); and links to online toxicology summaries. Here, we use data from ACToR to assess the toxicity data landscape for environmental chemicals., Data Synthesis: We show results for a set of 9,912 environmental chemicals being considered for analysis as part of the U.S. EPA ToxCast screening and prioritization program. These include high-and medium-production-volume chemicals, pesticide active and inert ingredients, and drinking water contaminants., Conclusions: Approximately two-thirds of these chemicals have at least limited toxicity summaries available. About one-quarter have been assessed in at least one highly curated toxicology evaluation database such as the U.S. EPA Toxicology Reference Database, U.S. EPA Integrated Risk Information System, and the National Toxicology Program.