Toward Machine Learning-Driven Mass Spectrometric Identification of Trichothecenes in the Absence of Standard Reference Materials.

While a significant body of work exists on the detection of commonly known trichothecene toxins, biological, environmental, and other transformational processes can generate many under-characterized and unknown modified trichothecenes. Lacking both analytical reference standards and associated mass spectral databases, identification of these modified compounds reflects both a challenge and a critical gap from forensic and public health perspectives. We report here the application of machine learning (ML) techniques toward identification of discriminative fragment ions from mass spectrometric data that can be exploited to detect evidence of type A and B trichothecenes. The goal of this work is to establish a new method for the identification of unknown, though structurally similar trichothecenes, by leveraging objective ML techniques. Discriminative fragments derived from a series of gradient-boosted machine learners are then used to develop ML-driven precursor ion scan (PIS) methods on a triple quadrupole mass spectrometer (QQQ) for screening of "unknown unknown" trichothecenes. Specifically, we apply the PIS method to a laboratory-synthesized trichothecene, a first step in demonstrating the power of alternative, machine learning-driven mass spectrometric methods.

Doubt in store: vaccine hesitancy among grocery workers during the COVID-19 pandemic.

The objective of this study was to assess the influence of workplace safety conditions alongside the World Health Organization's model of the "3 Cs", on grocery store workers' vaccine hesitancy concerning COVID-19. Data for this study come from the Arizona Frontline Workers Survey, a longitudin web-based survey of 770 grocery store workers in the state of Arizona (US) collected in July 2020 and January 2021. We utilized ordinary least squares and multinomial logistic regression analyses to assess predictors of hesitancy at our Wave 2. Thirty-nine percent of our sample reported being unlikely to get vaccinated against COVID-19. Two aspects of the "3 Cs" model, confidence and convenience, were correlated with lower levels of vaccine hesitancy while the perceptions of being protected by one's employer increased hesitancy. Our findings underscore the importance of workplace conditions for vaccine hesitancy and the need to include vaccine messaging in employers' safety practices.

Pipes or Prisms? Personal Networks, Network Mechanisms, and Formal Support Receipt In The Wake Of Deepwater Horizon Oil Spill.

Social networks are commonly discussed in reference to processes of disaster recovery but rarely explicitly measured. We employ a mixed-methods approach drawing upon the personal-network data of 265 oysterworkers in the wake of the Deepwater Horizon oil spill and qualitative accounts of individual experiences during the recovery process. We find evidence of two potential mechanisms linking network structure with the receipt of formal support: a networks-as-pipes approach linking networks and access to relevant information in the wake of a disaster and a networks-as-prisms approach where networks signal their social identities, shaping post-disaster actions and behaviors.

Environmental Risk Perceptions and Community Health: Arsenic, Air Pollution, and Threats to Traditional Values of the Hopi Tribe.

American Indian and Alaska Native populations experience chronic disparities in a wide range of health outcomes, many of which are associated with disproportionate exposures to environmental health hazards. In the American Southwest, many indigenous tribes experience challenges in securing access to sustainable and safe sources of drinking water, limiting air pollution emissions on and off tribal lands, and cleaning up hazardous contaminants left over from a legacy of natural resource extraction. To better understand how households perceive the risk of exposure to potential environmental health risks, we conducted six focus groups organized by age and geographic location on the Hopi reservation. Focus group participants (n = 41) were asked to reflect on changes in their natural and manmade environment and how their health might be influenced by any potential changes. By investigating these environmental risk perceptions, we were able to identify arsenic in drinking water and indoor air quality as significant exposures of concern. These risk perceptions were frequently anchored in personal and familial experiences with health problems such as cancer and asthma. Older focus group participants identified ongoing shifts away from tradition and cultural practices as increasing environmental health risks. Similar to other communities economically dependent on the extraction of natural resources, focus group participants described the need for behavioral modifications regarding environmental health risks rather than eliminating the sources of potential health risks entirely. Our results suggest the need for including traditional values and practices in future interventions to reduce environmental health risks.

Chemical Attribution of Fentanyl Using Multivariate Statistical Analysis of Orthogonal Mass Spectral Data.

Attribution of the origin of an illicit drug relies on identification of compounds indicative of its clandestine production and is a key component of many modern forensic investigations. The results of these studies can yield detailed information on method of manufacture, starting material source, and final product, all critical forensic evidence. In the present work, chemical attribution signatures (CAS) associated with the synthesis of the analgesic fentanyl, N-(1-phenylethylpiperidin-4-yl)-N-phenylpropanamide, were investigated. Six synthesis methods, all previously published fentanyl synthetic routes or hybrid versions thereof, were studied in an effort to identify and classify route-specific signatures. A total of 160 distinct compounds and inorganic species were identified using gas and liquid chromatographies combined with mass spectrometric methods (gas chromatography/mass spectrometry (GC/MS) and liquid chromatography-tandem mass spectrometry-time of-flight (LC-MS/MS-TOF)) in conjunction with inductively coupled plasma mass spectrometry (ICPMS). The complexity of the resultant data matrix urged the use of multivariate statistical analysis. Using partial least-squares-discriminant analysis (PLS-DA), 87 route-specific CAS were classified and a statistical model capable of predicting the method of fentanyl synthesis was validated and tested against CAS profiles from crude fentanyl products deposited and later extracted from two operationally relevant surfaces: stainless steel and vinyl tile. This work provides the most detailed fentanyl CAS investigation to date by using orthogonal mass spectral data to identify CAS of forensic significance for illicit drug detection, profiling, and attribution.

Visualizing Temporal Topic Embeddings with a Compass.

Dynamic topic modeling is useful at discovering the development and change in latent topics over time. However, present methodology relies on algorithms that separate document and word representations. This prevents the creation of a meaningful embedding space where changes in word usage and documents can be directly analyzed in a temporal context. This paper proposes an expansion of the compass-aligned temporal Word2Vec methodology into dynamic topic modeling. Such a method allows for the direct comparison of word and document embeddings across time in dynamic topics. This enables the creation of visualizations that incorporate temporal word embeddings within the context of documents into topic visualizations. In experiments against the current state-of-the-art, our proposed method demonstrates overall competitive performance in topic relevancy and diversity across temporal datasets of varying size. Simultaneously, it provides insightful visualizations focused on temporal word embeddings while maintaining the insights provided by global topic evolution, advancing our understanding of how topics evolve over time.

Psychological responses and resilience of people and communities impacted by the deepwater horizon oil spill.

On April 20, 2010, the BP Deepwater Horizon oil platform in the United States Gulf of Mexico exploded, killing 11 persons and resulting in a 5-month spill of more than 206 million gallons of oil, affecting more than 950 miles of shoreline. Our initial studies in Baldwin County, Alabama, and Franklin County, Florida, conducted while the oil spill was still in progress, showed high levels of clinically significant anxiety and depression in persons living in coastal communities. Income loss was the most significant driver of anxiety and depression, rather than direct influx or contact with oil. Ongoing studies of these groups and their communities have been conducted under the auspices of the National Institute of Environmental Health Sciences (NIEHS) Deepwater Horizon Research Consortium. A year after the spill, there was no significant change in levels of anxiety or depression in our cohort. Income loss continued to be associated with higher levels of psychopathology; findings were not associated with age, gender, education, or psychiatric history. Media exposure was associated with persistent hyperarousal. Findings support a model of chronic psychological disruption after the oil spill disaster. Community studies underscored the "corrosive" nature of this type of man-made disaster (as compared with natural disasters that have hit the region), with particular concerns expressed about the compensation process administered by British Petroleum and the parties that followed. Our research highlights the very real and long-lasting impact of such disasters on individuals and communities, extending well beyond the areas where there was direct exposure to oil.

Evaluation of polyanionic cyclodextrins as high affinity binding scaffolds for fentanyl.

Cyclodextrins (CDs) have been previously shown to display modest equilibrium binding affinities (Ka ~ 100-200 M-1) for the synthetic opioid analgesic fentanyl. In this work, we describe the synthesis of new CDs possessing extended thioalkylcarboxyl or thioalkylhydroxyl moieties and assess their binding affinity towards fentanyl hydrochloride. The optimal CD studied displays a remarkable affinity for the opioid of Ka = 66,500 M-1, the largest value reported for such an inclusion complex to date. One dimensional 1H Nuclear Magnetic Resonance (NMR) as well as Rotational Frame Overhauser Spectroscopy (2D-ROESY) experiments supported by molecular dynamics (MD) simulations suggest an unexpected binding behavior, with fentanyl able to bind the CD interior in one of two distinct orientations. Binding energies derived from the MD simulations work correlate strongly with NMR-derived affinities highlighting its utility as a predictive tool for CD candidate optimization. The performance of these host molecules portends their utility as platforms for medical countermeasures for opioid exposure, as biosensors, and in other forensic science applications.

Evaluation of 6-OxP-CD, an Oxime-based cyclodextrin as a viable medical countermeasure against nerve agent poisoning: Experimental and molecular dynamic simulation studies on its inclusion complexes with cyclosarin, soman and VX.

The ability of the cyclodextrin-oxime construct 6-OxP-CD to bind and degrade the nerve agents Cyclosarin (GF), Soman (GD) and S-[2-[Di(propan-2-yl)amino]ethyl] O-ethyl methylphosphonothioate (VX) has been studied using 31P-nuclear magnetic resonance (NMR) under physiological conditions. While 6-OxP-CD was found to degrade GF instantaneously under these conditions, it was found to form an inclusion complex with GD and significantly improve its degradation (t1/2 ~ 2 hrs) relative over background (t1/2 ~ 22 hrs). Consequently, effective formation of the 6-OxP-CD:GD inclusion complex results in the immediate neutralization of GD and thus preventing it from inhibiting its biological target. In contrast, NMR experiments did not find evidence for an inclusion complex between 6-OxP-CD and VX, and the agent's degradation profile was identical to that of background degradation (t1/2 ~ 24 hrs). As a complement to this experimental work, molecular dynamics (MD) simulations coupled with Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) calculations have been applied to the study of inclusion complexes between 6-OxP-CD and the three nerve agents. These studies provide data that informs the understanding of the different degradative interactions exhibited by 6-OxP-CD with each nerve agent as it is introduced in the CD cavity in two different orientations (up and down). For its complex with GF, it was found that the oxime in 6-OxP-CD lies in very close proximity (PGF⋯OOxime ~ 4-5 Å) to the phosphorus center of GF in the 'downGF' orientation for most of the simulation accurately describing the ability of 6-OxP-CD to degrade this nerve agent rapidly and efficiently. Further computational studies involving the center of masses (COMs) for both components (GF and 6-OxP-CD) also provided some insight on the nature of this inclusion complex. Distances between the COMs (ΔCOM) lie closer in space in the 'downGF' orientation than in the 'upGF' orientation; a correlation that seems to hold true not only for GF but also for its congener, GD. In the case of GD, calculations for the 'downGD' orientation showed that the oxime functional group in 6-OxP-CD although lying in close proximity (PGD⋯OOxime ~ 4-5 Å) to the phosphorus center of the nerve agent for most of the simulation, adopts another stable conformation that increase this distance to ~ 12-14 Å, thus explaining the ability of 6-OxP-CD to bind and degrade GD but with less efficiency as observed experimentally (t1/2 ~ 4 hr. vs. immediate). Lastly, studies on the VX:6-OxP-CD system demonstrated that VX does not form a stable inclusion complex with the oxime-bearing cyclodextrin and as such does not interact in a way that is conducive to an accelerated degradation scenario. Collectively, these studies serve as a basic platform from which the development of new cyclodextrin scaffolds based on 6-OxP-CD can be designed in the development of medical countermeasures against these highly toxic chemical warfare agents.

31P-edited diffusion-ordered 1H NMR spectroscopy for the spectral isolation and identification of organophosphorus compounds related to chemical weapons agents and their degradation products.

Organophosphorus compounds represent a large class of molecules that include pesticides, flame-retardants, biologically relevant molecules, and chemical weapons agents (CWAs). The detection and identification of organophosphorus molecules, particularly in the cases of pesticides and CWAs, are paramount to the verification of international treaties by various organizations. To that end, novel analytical methodologies that can provide additional support to traditional analyses are important for unambiguous identification of these compounds. We have developed an NMR method that selectively edits for organophosphorus compounds via (31)P-(1)H heteronuclear single quantum correlation (HSQC) and provides an additional chromatographic-like separation based on self-diffusivities of the individual species via (1)H diffusion-ordered spectroscopy (DOSY): (1)H-(31)P HSQC-DOSY. The technique is first validated using the CWA VX (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate) by traditional two-dimensional DOSY spectra. We then extend this technique to a complex mixture of VX degradation products and identify all the main phosphorus-containing byproducts generated after exposure to a zinc-cyclen organometallic homogeneous catalyst.

NMR spectroscopic investigation of inclusion complexes between cyclodextrins and the neurotoxin tetramethylenedisulfotetramine.

The binding stoichiometry, strength and structure of inclusion complexes formed between the neurotoxin tetramethylenedisulfotetramine (TETS) and both native and modified cyclodextrins (CyDs) were investigated using nuclear magnetic resonance (NMR) spectroscopy. Of all six examined cases, native ß-cyclodextrin (ß-CyD) and its chemically modified counterpart heptakis-(2,3,6-tris-(2-hydroxypropyl))-ß-cyclodextrin (2HP-ß-CyD) were found to associate most strongly with TETS as reflected in the magnitude of their binding constants (K = 537 ± 26 M(-1) for ß-CyD and K = 514 ± 49 M(-1) for 2HP-ß-CyD). Two-dimensional rotating-frame Overhauser effect spectroscopy NMR experiments confirm close proximity of the TETS molecule to both ß-CyD and 2HP-ß-CyD as intermolecular, through-space interactions between the H3 and H5 protons located in the interior of the CyD cavity and the methylene protons of TETS were identified.

Draft Genome Sequences of Pseudomonas sp. Strains MWU13-2100 and MWU13-2105 Isolated from Wild Cranberry Bog Soil in the Cape Cod National Seashore.

Pseudomonas sp. strains MWU13-2100 and MWU13-2105 were isolated from a wild cranberry bog with Pipestone loamy coarse sand soil in Truro, Massachusetts, and taxonomically assigned based on whole-genome sequences. The draft genomes are most closely related to P. batumici (41.4% and 41.8% dDDHd4), but with only 50.8 dDDHd4 to each other.

Essential but Ill-Prepared: How the COVID-19 Pandemic Affects the Mental Health of the Grocery Store Workforce.

OBJECTIVES: Frontline essential workers face elevated risks of exposure to COVID-19 because of the interactive nature of their jobs, which require high levels of interaction with the general public and coworkers. The impact of these elevated risks on the mental health of essential workers, especially outside the health care sector, is not well studied. To address this knowledge gap, we examined correlations between perceptions of workplace risks and mental health distress among grocery store workers in Arizona. METHODS: We collected the first statewide sample of essential workers outside the health care sector focused on mental health and well-being. A total of 3344 grocery store workers in Arizona completed an online survey in July 2020. We used multiple regression models to identify demographic and work-based correlates of mental health distress. RESULTS: Levels of mental health distress among respondents were high: 557 of 3169 (17.6%) reported severe levels and 482 of 3168 (15.2%) reported moderate levels. Perceptions of workplace safety were strongly correlated with significantly reduced levels of mental health distress (ß = -1.44; SE = 0.20) and reduced perceived stress (ß = -0.97; SE = 0.16). Financially disadvantaged workers and employees aged <55 reported high levels of mental health distress. Perceptions of safety and protection in the workplace were significantly correlated with availability of safety trainings, social distancing, and policies governing customer behaviors. CONCLUSIONS: Lacking sufficient workplace protections, grocery store employees in Arizona experienced high levels of mental health distress during the COVID-19 pandemic. Providing clear federal and state policies to employers to guide implementation of workplace protections may help reduce sources of mental health distress.

Countermeasures for Preventing and Treating Opioid Overdose.

The only medication available currently to prevent and treat opioid overdose (naloxone) was approved by the US Food and Drug Administration (FDA) nearly 50 years ago. Because of its pharmacokinetic and pharmacodynamic properties, naloxone has limited utility under some conditions and would not be effective to counteract mass casualties involving large-scale deployment of weaponized synthetic opioids. To address shortcomings of current medical countermeasures for opioid toxicity, a trans-agency scientific meeting was convened by the US National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIAID/NIH) on August 6 and 7, 2019, to explore emerging alternative approaches for treating opioid overdose in the event of weaponization of synthetic opioids. The meeting was initiated by the Chemical Countermeasures Research Program (CCRP), was organized by NIAID, and was a collaboration with the National Institute on Drug Abuse/NIH (NIDA/NIH), the FDA, the Defense Threat Reduction Agency (DTRA), and the Biomedical Advanced Research and Development Authority (BARDA). This paper provides an overview of several presentations at that meeting that discussed emerging new approaches for treating opioid overdose, including the following: (1) intranasal nalmefene, a competitive, reversible opioid receptor antagonist with a longer duration of action than naloxone; (2) methocinnamox, a novel opioid receptor antagonist; (3) covalent naloxone nanoparticles; (4) serotonin (5-HT)1A receptor agonists; (5) fentanyl-binding cyclodextrin scaffolds; (6) detoxifying biomimetic "nanosponge" decoy receptors; and (7) antibody-based strategies. These approaches could also be applied to treat opioid use disorder.

The role of employers and supervisors in promoting pesticide safety behavior among Florida farmworkers.

BACKGROUND: Farmworkers in Florida's nursery and fernery industries have an elevated risk of exposure to chemical pesticides due to the enclosed nature of their workplaces and their close contact with pesticide-treated plant material. Farmworkers' beliefs about chemical exposures and their perception of employer's or supervisor's valuing of safety may limit the practice of workplace hygiene. METHODS: Three hundred eighty-two surveys from workers in the nursery and fernery industries in North Central Florida were collected as part of the Together for Agricultural Safety (TAS) Project from 1999-2001. Univariate analyses and multivariate Ordinary Least Squares regression are used to examine the role of individual and structural characteristics on handwashing practices. RESULTS: Workplace practices such as the provision of written notices of recent pesticide application and the provision of convenient handwashing facilities are important predictors of workplace hygiene. Although farmworker attitudes and beliefs towards the utility of such practices and potential hazards are associated with behavior, they are less significant than the structural variables. CONCLUSIONS: In order for farmworkers to engage in safety behavior that will protect their health, they must be adequately instructed and supported by employers and/or supervisors.

"The Community Helped Me:" Community Cohesion and Environmental Concerns in Personal Assessments of Post-Disaster Recovery.

This study investigates long-term appraisals of community recovery after a major environmental disaster. Specifically, we conducted a survey of 351 individuals living in coastal counties in Alabama and Florida on the five-year anniversary of the Deepwater Horizon oil spill. Using mixed methods that combined content analysis and ordinary least squares regression, we find that residents who believe they live in a community where neighbors help each other are more likely to see their communities as recovering. Conversely, reporting major effects from environmental problems, like lost fishing income, reduces perceptions of community recovery. Five years after the oil spill a majority of respondents saw little economic recovery and almost half perceived low environmental recovery. This reflects the importance of the environment to the long-term health and success of areas dependent on natural resources. It also suggests the need for directing funding toward community-level programs and preserving shared natural resources post-disaster.

Development of Guidelines to Improve the Effectiveness of Community Advisory Boards in Health Research.

BACKGROUND: Community advisory boards (CABs) are a common community engagement strategy. Tools for developing CABs that are accessible to academic-community partnerships are limited. This article describes the process and partnership with the Hopi Tribe to develop CAB guidelines as a tool for research funded by the Center for Indigenous Environmental Health Research (CIEHR) and nonaffiliated projects. METHODS: The CAB guidelines consist of three sections: formation, operation, and sustainability and evaluation. Each section includes best practices and interactive worksheets. The CAB guidelines were piloted with the Hopi Tribe to determine feasibility and relevance. RESULTS: The CAB guidelines were well-received by the tribal CAB. Some of the worksheets were difficult to complete because they did not represent their perspectives or introduced potential tension in CAB interactions. Revisions were made accordingly. CONCLUSIONS: Future evaluation and broad dissemination of the CAB guidelines will promote the use and effectiveness of CABs in health research.

A Review of the Literature on Community Resilience and Disaster Recovery.

PURPOSE OF REVIEW: The concept of resilience continues to grow in influence and prominence in national and international programs seeking to improve individual and collective capacity to prepare for and respond to disasters. This review of the literature published in 2018 examines how disaster scholars and professionals are conceptualizing and applying the concept of community disaster resilience. RECENT FINDINGS: Three trends in the literature on community disaster resilience are observed: (1) advancements in the measurement of resilience continue to refine the concept and its related mechanisms using both primary and secondary data, (2) social capital continues to be a central mechanism through which community resilience reduces disaster impact and enhances recovery, and (3) programs across the globe are advancing the practice of improving resilience through community interventions to enhancing adaptive capacities. Community disaster resilience offers much promise as a guiding paradigm for the promotion of disaster risk reduction and the enabling of disaster recovery through attention to, and investment in, local capacities for adaptation to a changing and uncertain environment. However, there remains work to be done in the clarification of the concept and the operationalization of the mechanisms leading to enhancing community capacity for resilience.

Part 3: Solid phase extraction of Russian VX and its chemical attribution signatures in food matrices and their detection by GC-MS and LC-MS.

Chemical attribution signatures indicative of O-isobutyl S-(2-diethylaminoethyl) methylphosphonothioate (Russian VX) synthetic routes were investigated in spiked food samples. Attribution signatures were identified using a multifaceted approach: Russian VX was synthesized using six synthetic routes and the chemical attribution signatures identified by GC-MS and LC-MS. Three synthetic routes were then down selected and spiked into complex matrices: bottled water, baby food, milk, liquid eggs, and hot dogs. Sampling and extraction methodologies were developed for these materials and used to isolate the attribution signatures and Russian VX from each matrix. Recoveries greater than 60% were achieved for most signatures in all matrices; some signatures provided recoveries greater than 100%, indicating some degradation during sample preparation. A chemometric model was then developed and validated with the concatenated data from GC-MS and LC-MS analyses of the signatures; the classification results of the model were > 75% for all samples. This work is part three of a three-part series in this issue of the United States-Sweden collaborative efforts towards the understanding of the chemical attribution signatures of Russian VX in crude materials and in food matrices.

Statistical analysis of the chemical attribution signatures of 3-methylfentanyl and its methods of production.

Chemical attribution of the origin of an illegal drug is a key component of forensic efforts aimed at combating illicit and clandestine manufacture of drugs and pharmaceuticals. The results of these studies yield detailed information on synthesis byproducts, reagents, and precursors that can be used to identify the method of manufacture. In the present work, chemical attribution signatures (CAS) associated with the synthesis of the analgesic 3-methylfentanyl, N-(3-methyl-1-phenethylpiperidin-4-yl)-N-phenylpropanamide, were investigated. Eighteen crude samples from six synthesis methods were generated, the analysis of which was used to identify signatures (i.e. chemical compounds) that were important in the discrimination of synthetic route. These methods were carefully selected to minimize the use of scheduled precursors, complicated laboratory equipment, number of steps, and extreme reaction conditions. Using gas and liquid chromatographies combined with time-of-flight mass spectrometry (GC-QTOF and LC-QTOF) over 160 distinct species were monitored. Analysis of this combined data set was performed using modern machine learning techniques capable of reducing the size of the data set, prioritizing key chemical attribution signatures, and identifying the method of production for blindly synthesized 3-methylfentanyl materials.