Potential consequences of nitric oxide release: An improved model informing worker safety.

Both nitric oxide (NO) and nitrogen dioxide (NO2) gasses are toxic to humans but are commonly found in industrial settings such as semiconductor manufacturing sites. Due to the spontaneous oxidation of NO to NO2 under ambient conditions, individuals working with NO may in fact be exposed to both gasses in the case of an accidental release. Unfortunately, most safety materials provided to NO users do not address the potential for associated NO2 toxicity, and, until now, models developed to predict health consequences following a release of NO have not appropriately considered the oxidation kinetics nor the toxicity of both NO and NO2 in their assessments. This paper describes an improved multi-module model that addresses these limitations and explores whether facilities using NO should consider adopting measures that can mitigate the simultaneous health effects of both gasses. The model predicts the morbidity (intoxication/injury), mortality (death), and treatment outcomes that may arise following an industrial NO release by first calculating the doses of both NO and NO2 received by exposed individuals and then applying newly defined toxicity parameters for NO and NO2 to assign dose-dependent probabilities for the onset of intoxication and/or death and the ability of appropriate treatment(s) to save lives. Modeling results indicate low risk to worker health in the likeliest release scenarios while identifying less likely situations that carry substantially higher risk. Moreover, these results indicate that risks to worker health can be mitigated with simple measures like maintaining reliable alarms, adequate ventilation, and on-site supplies of methylene blue, as well as encouraging quick responses by personnel. With appropriate parameterization, the improved modeling framework is generalizable to any chemical release, especially multi-hazard releases resulting from the conversion of one toxic compound into another under likely environmental conditions. By directly addressing the toxicities of multiple compounds, the improved model presents a more realistic picture of the potential health consequences of a chemical release. This generalizable framework for modeling of multi-hazard chemical releases can inform preparedness and risk mitigation strategies for NO release events.

Frequency of Leaks from Conical Centrifuge Tubes.

Introduction: Threaded conical centrifuge tubes are ubiquitous in biological laboratories and are frequently used for the storage/transport of potentially biohazardous samples. However, limited data are available on how frequently and from where these tubes leak. These data are valuable for laboratory biorisk management and to inform future studies on risks arising from the routine use of laboratory consumables. Methods: The frequency of leaks from threaded conical centrifuge tubes was tested using a Glo Germ solution as a tracer. Conical tubes (15 and 50 mL) from several brands were filled, inverted, and placed on their side on the benchtop. After 1 h, the presence or absence of leaks on the benchtop surface, tube threads, and exterior was recorded. Results: We observed that liquid leaked out of tubes that were apparently properly threaded in 2% of 15 mL tubes (confidence interval [95% CI] 1.4-2.6) and 1.4% of 50 mL tubes (95% CI 0.2-1.5). After opening, liquid was found on the threads on the outside of the tube in 20% of 15 mL tubes (95% CI 10-31) and 14% of 50 mL tubes (95% CI 1-28). We did not find sufficient evidence that differences in leak rates among brands were practically significant. Conclusions: The fact that leaks were not uncommonly observed from conical centrifuge tubes suggests that mitigations for any hazard posed by a leak should be a component of every biorisk management strategy for protocols involving the manipulation of hazardous substances in these tubes. Further research should be conducted on other activities that could cause tubes to leak (such as centrifugation or vortexing) and should be completed to understand the risks associated with this consumable. Research into the costs and benefits of mitigating the risk of leaks from conical tubes is recommended.

Beyond gain of function: strengthening oversight of research with potential pandemic pathogens.

In 2017, the Department of Health and Human Services adopted a policy, known as the P3CO Framework, to govern proposed research that could enhance the lethality or transmissibility of a potential pandemic pathogen. The prospect of a human-made virus with artificially enhanced lethality and transmissibility has raised serious biosafety and biosecurity concerns. The COVID-19 pandemic has generated new concerns about the risks posed by such research. Even if the origins of the pandemic are presumed or proven to be the result of a natural zoonotic spillover event, the pandemic has placed greater scrutiny on research that could generate pandemic-capable viruses and dramatically illustrated the consequences if such a virus were released from a laboratory. This article assesses the strengths and weaknesses of the P3CO Framework and provides recommendations for strengthening oversight of research with potential pandemic pathogens. The P3CO Framework should be replaced by a national policy that would apply to all relevant research, regardless of the source of funding and be implemented by a new national agency for biorisk management. This new policy would need to be accompanied by a comprehensive analysis of potential pandemic pathogen risks, clear guidance on how to identify research that falls within the scope of the policy, a rigorous process for reviewing the risks and benefits of such research, and criteria for determining the appropriate measures needed to conduct such research safely, securely, and responsibly.

Meta-Analysis on the Health Effects Resulting from Evacuation or Relocation.

OBJECTIVE: Evacuation and relocation are key actions used to protect the public in response to natural or technological disasters, but there are inherent risks to both. Unfortunately, these risks have not been fully quantified, which limits the ability of emergency managers and the public to effectively balance the risks and benefits of evacuation or relocation. This work provides quantitative data on the risks of health effects from displacement following evacuation or relocation. METHODS: Researchers performed a literature review and meta-analysis of published studies and quantified risks of 14 different health effects, including both physical and socio-behavioral outcomes, from studies of 9 different disaster types. RESULTS: The findings show statistically significant increases in 9 of the 14 health effects in displaced populations, indicating an increased likelihood of experiencing detrimental health effects compared with nondisplaced populations. A pooled analysis of all negative health effects found an odds ratio of 1.49 (95% confidence interval: 1.24-1.79), which shows a significant relationship between displacement and negative health outcomes. CONCLUSIONS: These findings demonstrate that evacuated or relocated populations have an increased risk of experiencing negative health effects associated with displacement. The broad number of disaster types included mean that findings are applicable to any emergency evacuation or relocation.

Lessons Learned from the Design, Construction, and Commissioning of a Retrofitted Arthropod Containment Level 3 Insectary.

Arthropods are vectors for many pathogens that significantly harm human and animal health globally, and research into vector-borne diseases is of critical public health importance. Arthropods present unique risks for containment, and therefore insectary facilities are essential to the safe handling of arthropod-borne hazards. In 2018, the School of Life Sciences at Arizona State University (ASU) began the process to build a level 3 arthropod containment (ACL-3) facility. Even with the COVID-19 pandemic, it took more than 4 years for the insectary to be granted a Certificate of Occupancy. At the request of the ASU Environmental Health and Safety team, Gryphon Scientific, an independent team with biosafety and biological research expertise, studied the project lifecycle through the design, construction, and commissioning of the ACL-3 facility with the goal of identifying lessons learned from the delayed timeline. These lessons learned convey insight into best practices for assessing potential facility sites, anticipating challenges with retrofitted construction, preparing for commissioning, equipping the project team with necessary expertise and expectations, and supplementing the gaps in available containment guidance. Several unique mitigations designed by the ASU team to address research risks not specifically addressed in the American Committee of Medical Entomology Arthropod Containment Guidelines are also described. Completion of the ACL-3 insectary at ASU was delayed, but the team thoroughly assessed potential risks and enabled appropriate practices for the safe handling of arthropod vectors. These efforts will enhance future ACL-3 construction by helping to avoid similar setbacks and streamlining progress from concept to operation.

Rate of Splashes When Opening Microfuge Tubes with Various Methods.

Introduction: Snap-cap microcentrifuge tubes are ubiquitous in biological laboratories. However, limited data are available on how frequently splashes occur when opening them. These data would be valuable for biorisk management in the laboratory. Methods: The frequency of splashes from opening snap-cap tubes using four different methods was tested. The splash frequency for each method was measured on the benchtop surface and on the experimenter's gloves and smock, using a Glo Germ solution as a tracer. Results: Splashes occurred very frequently when opening microcentrifuge snap-cap tubes, no matter which method was used to open the tube. The highest rate of splashes on all surfaces was observed with the one-handed (OH) opening method compared with two-handed methods. Across all methods, the highest rate of splashes was observed on the opener's gloves (70-97%) compared with the benchtop (2-40%) or the body of the researcher (0-7%). Conclusions: All tube opening methods we studied frequently caused splashes, with the OH method being the most error-prone but no two-handed method being clearly superior to any other. In addition to posing an exposure risk to laboratory personnel, experimental repeatability may be affected due to loss of volume when using snap-cap tubes. The rate of splashes underscores the importance of secondary containment, personal protective equipment, and good protocols for decontamination. When working with especially hazardous materials, alternatives to snap-cap tubes (such as screw cap tubes) should be strongly considered. Future studies can examine other methods of opening snap-cap tubes to determine whether a truly safe method exists.

Concepts to Bolster Biorisk Management.

The rapid increase in the power of the life sciences has not been accompanied by a proportionate increase in the sophistication of biorisk management. Through conversations with thought leaders in biosafety and biosecurity, we have identified 19 concepts that are critical for biorisk management to continue to ensure the responsible and safe conduct of the life sciences in the future. Our work is not meant to be a comprehensive list, but rather a collection of topics that we hope will spark dialogue in the policy, research, and biorisk management communities.

Occupational Safety and Health and Illicit Opioids: State of the Research on Protecting Against the Threat of Occupational Exposure.

The nationwide opioid crisis continues to affect not only people who use opioids but also communities at large by increasing the risk of accidental occupational exposure to illicit opioids. In addition, the emergence of highly potent synthetic opioids such as fentanyl and carfentanil increases the need to protect workers who may encounter unknown drug substances during job activities. To support the National Institute for Occupational Safety and Health Opioids Research Gaps Working Group, we examined the state of the literature concerning methods to protect workers against accidental occupational exposure to illicit opioids, and have identified unmet research needs concerning personal protective equipment, decontamination methods, and engineering controls. Additional studies are needed to overcome gaps in technical knowledge about personal protective equipment, decontamination, and control methods, and gaps in understanding how these measures are utilized by workers. Increasing our knowledge of how to protect against exposure to illicit opioids has the potential to improve occupational health across communities.

Bioengineering horizon scan 2020.

Horizon scanning is intended to identify the opportunities and threats associated with technological, regulatory and social change. In 2017 some of the present authors conducted a horizon scan for bioengineering (Wintle et al., 2017). Here we report the results of a new horizon scan that is based on inputs from a larger and more international group of 38 participants. The final list of 20 issues includes topics spanning from the political (the regulation of genomic data, increased philanthropic funding and malicious uses of neurochemicals) to the environmental (crops for changing climates and agricultural gene drives). The early identification of such issues is relevant to researchers, policy-makers and the wider public.

Modeling the Optimum Prussian Blue Treatment for Acute Radiation Syndrome Following 137Cs Ingestion.

Accidents or radiological attacks may lead to ingestion of Cs by large numbers of the public. This work models the efficacy of Prussian blue, the medical countermeasure for internal contamination with Cs, to prevent acute radiation syndrome as a function of the duration of treatment and the time that treatment starts after uptake. Risk of acute radiation syndrome is modeled using the International Commission on Radiological Protection's acute radiation hazard model. Dose rates to target organs from Cs ingestion were based on the data published by the US Environmental Protection Agency and the retention of Cs in the reference man. Modeling found that treatment is most effective if begun within 15 d of ingestion, and the course length should be at least 75 d to mitigate cancer risk and 290 d to mitigate fatalities due to acute radiation syndrome. Both of these course lengths are much longer than the minimum Prussian blue treatment regimen of 30 d. Extending the treatment time for contaminated individuals would increase demand for Prussian blue following an accident or attack and in turn, would require a larger stockpile of Prussian blue to meet demand. Not enough data is available to determine if this longer treatment time would lead to adverse medical outcomes due to the toxicity of the treatment itself.

Modeling Cutaneous Radiation Injury from Fallout.

OBJECTIVE: Beta radiation from nuclear weapons fallout could pose a risk of cutaneous radiation injury (CRI) to evacuating populations but has been investigated only cursorily. This work examines 2 components of CRI necessary for estimating the potential public health consequences of exposure to fallout: dose protraction and depth of dose. METHODS: Dose protraction for dry and moist desquamation was examined by adapting the biological effective dose (BED) calculation to a hazard function calculation similar to those recommended by the National Council on Radiation Protection and Measurements for other acute radiation injuries. Depth of burn was examined using Monte Carlo neutral Particle version 5 to model the penetration of beta radiation from fallout to different skin tissues. RESULTS: Nonlinear least squares analysis of the BED calculation estimated the hazard function parameter θ1 (dose rate effectiveness factors) as 25.5 and 74.5 (Gy-eq)2 h-1 for dry and moist desquamation, respectively. Depth of dose models revealed that beta radiation is primarily absorbed in the dead skin layers and basal layer and that dose to underlying tissues is small (<5% of dose to basal layer). CONCLUSIONS: The low relative dose to tissues below the basal layer suggests that radiation-induced necrosis or deep skin burns are unlikely from direct skin contamination with fallout. These results enable future modeling studies to better examine CRI risk and facilitate effectively managing and treating populations with specialized injuries from a nuclear detonation. (Disaster Med Public Health Preparedness. 2019;13:463-469).

Chemical, Biological, Radiological, Nuclear, and Explosive (CBRNE) Science and the CBRNE Science Medical Operations Science Support Expert (CMOSSE).

A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.

Screening Internal Contamination of Inhaled and Ingested Radionuclides with Hand-held Survey Meters.

During the aftermath of a radiological accident or attack, the rapid identification of individuals who have internalized medically significant amounts of material is paramount to guide medical and public health decisions. This paper explores the utility of hand-held, pancake GM detectors to determine if an individual has inhaled Sr, Cs, Pu, Pu, or Am in quantities requiring treatment. Additionally, ingestion of Sr or Cs was considered. Both Sr and Cs were modeled in equilibrium with their progeny, but the progeny of Pu, Pu, and Am were excluded. Treatment thresholds are defined using the National Council on Radiation Protection & Measurements' (NCRP) clinical decision guides (CDGs). Using Monte Carlo N-Particle (MCNP) modeling software, a human phantom and detector were modeled to determine the activity required to achieve a detector reading of twice background 1, 7, or 30 d post-ingestion or post-inhalation. Modeling found that inhaled Pu, Pu, and Am are detectable only if the contaminated individual inhaled thousands-fold more material than the CDG. This lack of detectability means that hand-held GM detectors are inappropriate for initial screening for americium or plutonium and that more intensive screening is necessary to confirm suspected contamination. Cesium-137, by contrast, could be detected at levels 10- to 100-fold lower than the amount requiring treatment, allowing quick differentiation between contaminated and uncontaminated individuals. Surprisingly, Sr was detectable within a factor of 2 of the amount requiring treatment. Detection of Sr was due primarily to bremsstrahlung radiation from beta interactions with calcium in bone. While rapid screening could identify individuals contaminated by Cs and possibly with Sr, further screening of identified individuals is necessary to establish medical need. However, these contaminated individuals could still be prioritized for further testing and possible presumptive treatment. Based on the findings of this study, concepts of operation for the use of hand-held survey meters should be developed for the screening of individuals potentially internally contaminated with Cs and Sr.

Review of Cases of Occult Radiation Exposure and an Analysis of Time to Diagnosis.

Radiation sickness is challenging to diagnose, and the diagnosis is often based on nonclinical data. In accidents where patients are not aware of their exposure to radiation (so-called "occult exposures"), a correct diagnosis can take weeks or months. The purpose of this study is to review the time to diagnosis of radiation sickness for occult exposures where neither the physician nor the patients are aware of their exposure. We reviewed eight case reports involving occult exposures and examined the factors that contributed to a diagnosis. We found that an average of 23 d after exposure were required for diagnosis, regardless of route of intake. In only one case was radiation injury diagnosed within the first week. Although all but one of these cases occurred in the developing world, the factors confounding diagnosis are common to the U.S. medical system. Therefore, an urgent need exists for properly training physicians on radiation sickness so they can more quickly diagnose and treat radiation exposures when the patients are unaware of the exposure event.

Basic Scholarship in Biosafety Is Critically Needed To Reduce Risk of Laboratory Accidents.

Our firm conducted a risk/benefit assessment of "gain-of-function" research, as part of the deliberative process following a U.S. moratorium on the research (U.S. Department of Health and Human Services, U.S. Government Gain-of-Function Deliberative Process and Research Funding Pause on Selected Gain-of-Function Research Involving Influenza, MERS, and SARS Viruses, 2014). Due to significant missing but theoretically acquirable data, our biosafety assessment faced limitations, and we were forced to provide a relative, instead of absolute, measure of risk (Gryphon Scientific, LLC, Risk and Benefit Analysis of Gain of Function Research, 2016). Here, we argue that many of these types of missing data represent large and stunning gaps in our knowledge of biosafety and argue that these missing data, once acquired via primary research efforts, would improve biosafety risk assessments and could be incorporated into biosafety practices to reduce risk of accidents. Governments invest billions in biological research; at least a small fraction of this support is warranted to prevent biological accidents.

Estimating Risk of Hematopoietic Acute Radiation Syndrome in Children.

Following a radiological terrorist attack or radiation accident, the general public may be exposed to radiation. Historically, modeling efforts have focused on radiation effects on a "reference man"-a 70-kg, 180-cm-tall, 20- to 30-y-old male-which does not adequately reflect radiation hazard to special populations, particularly children. This work examines the radiosensitivity of children with respect to reference man to develop a set of parameters for modeling hematopoetic acute radiation syndrome in children. This analysis was performed using animal studies and the results verified using data from medical studies. Overall, the hematopoietic system in children is much more radiosensitive than that in adults, with the LD50 for children being 56% to 91% of the LD50 of adults, depending on age.

Advancing Symptom Science Through Symptom Cluster Research: Expert Panel Proceedings and Recommendations.

An overview of proceedings, findings, and recommendations from the workshop on "Advancing Symptom Science Through Symptom Cluster Research" sponsored by the National Institute of Nursing Research (NINR) and the Office of Rare Diseases Research, National Center for Advancing Translational Sciences, is presented. This workshop engaged an expert panel in an evidenced-based discussion regarding the state of the science of symptom clusters in chronic conditions including cancer and other rare diseases. An interdisciplinary working group from the extramural research community representing nursing, medicine, oncology, psychology, and bioinformatics was convened at the National Institutes of Health. Based on expertise, members were divided into teams to address key areas: defining characteristics of symptom clusters, priority symptom clusters and underlying mechanisms, measurement issues, targeted interventions, and new analytic strategies. For each area, the evidence was synthesized, limitations and gaps identified, and recommendations for future research delineated. The majority of findings in each area were from studies of oncology patients. However, increasing evidence suggests that symptom clusters occur in patients with other chronic conditions (eg, pulmonary, cardiac, and end-stage renal disease). Nonetheless, symptom cluster research is extremely limited and scientists are just beginning to understand how to investigate symptom clusters by developing frameworks and new methods and approaches. With a focus on personalized care, an understanding of individual susceptibility to symptoms and whether a "driving" symptom exists that triggers other symptoms in the cluster is needed. Also, research aimed at identifying the mechanisms that underlie symptom clusters is essential to developing targeted interventions.