-
BMJ Open Oct 2020The USA has the highest rate of community gun violence of any developed democracy. There is an urgent need to develop feasible, scalable and community-led interventions...
INTRODUCTION
The USA has the highest rate of community gun violence of any developed democracy. There is an urgent need to develop feasible, scalable and community-led interventions that mitigate incident gun violence and its associated health impacts. Our community-academic research team received National Institutes of Health funding to design a community-led intervention that mitigates the health impacts of living in communities with high rates of gun violence.
METHODS AND ANALYSIS
We adapted 'Building Resilience to Disasters', a conceptual framework for natural disaster preparedness, to guide actions of multiple sectors and the broader community to respond to the man-made disaster of gun violence. Using this framework, we will identify existing community assets to be building blocks of future community-led interventions. To identify existing community assets, we will conduct social network and spatial analyses of the gun violence episodes in our community and use these analyses to identify people and neighbourhood blocks that have been successful in avoiding gun violence. We will conduct qualitative interviews among a sample of individuals in the network that have avoided violence (n=45) and those living or working on blocks that have not been a location of victimisation (n=45) to identify existing assets. Lastly, we will use community-based system dynamics modelling processes to create a computer simulation of the community-level contributors and mitigators of the effects of gun violence that incorporates local population-based based data for calibration. We will engage a multistakeholder group and use themes from the qualitative interviews and the computer simulation to identify feasible community-led interventions.
ETHICS AND DISSEMINATION
The Human Investigation Committee at Yale University School of Medicine (#2000022360) granted study approval. We will disseminate study findings through peer-reviewed publications and academic and community presentations. The qualitative interview guides, system dynamics model and group model building scripts will be shared broadly.
Topics: Computer Simulation; Disasters; Gun Violence; Humans; Residence Characteristics; Violence
PubMed: 33040016
DOI: 10.1136/bmjopen-2020-040277 -
Journal of the American Medical... Jul 2021Artificial intelligence (AI) is critical to harnessing value from exponentially growing health and healthcare data. Expectations are high for AI solutions to effectively...
Artificial intelligence (AI) is critical to harnessing value from exponentially growing health and healthcare data. Expectations are high for AI solutions to effectively address current health challenges. However, there have been prior periods of enthusiasm for AI followed by periods of disillusionment, reduced investments, and progress, known as "AI Winters." We are now at risk of another AI Winter in health/healthcare due to increasing publicity of AI solutions that are not representing touted breakthroughs, and thereby decreasing trust of users in AI. In this article, we first highlight recently published literature on AI risks and mitigation strategies that would be relevant for groups considering designing, implementing, and promoting self-governance. We then describe a process for how a diverse group of stakeholders could develop and define standards for promoting trust, as well as AI risk-mitigating practices through greater industry self-governance. We also describe how adherence to such standards could be verified, specifically through certification/accreditation. Self-governance could be encouraged by governments to complement existing regulatory schema or legislative efforts to mitigate AI risks. Greater adoption of industry self-governance could fill a critical gap to construct a more comprehensive approach to the governance of AI solutions than US legislation/regulations currently encompass. In this more comprehensive approach, AI developers, AI users, and government/legislators all have critical roles to play to advance practices that maintain trust in AI and prevent another AI Winter.
Topics: Accreditation; Artificial Intelligence; Delivery of Health Care; Health Facilities; Trust
PubMed: 33895824
DOI: 10.1093/jamia/ocab065 -
Proceedings of the National Academy of... Dec 2023Thrombocytopenia, hemorrhage, anemia, and infection are life-threatening issues following accidental or intentional radiation exposure. Since few therapeutics are...
Thrombocytopenia, hemorrhage, anemia, and infection are life-threatening issues following accidental or intentional radiation exposure. Since few therapeutics are available, safe and efficacious small molecules to mitigate radiation-induced injury need to be developed. Our previous study showed the synthetic TLR2/TLR6 ligand fibroblast stimulating lipopeptide (FSL-1) prolonged survival and provided MyD88-dependent mitigation of hematopoietic acute radiation syndrome (H-ARS) in mice. Although mice and humans differ in TLR number, expression, and function, nonhuman primate (NHP) TLRs are like those of humans; therefore, studying both animal models is critical for drug development. The objectives of this study were to determine the efficacy of FSL-1 on hematopoietic recovery in small and large animal models subjected to sublethal total body irradiation and investigate its mechanism of action. In mice, we demonstrate a lack of adverse effects, an easy route of delivery (subcutaneous) and efficacy in promoting hematopoietic progenitor cell proliferation by FSL-1. NHP given radiation, followed a day later with a single subcutaneous administration of FSL-1, displayed no adversity but showed elevated hematopoietic cells. Our analyses revealed that FSL-1 promoted red blood cell development and induced soluble effectors following radiation exposure. Cytologic analysis of bone marrow aspirates revealed a striking enhancement of mononuclear progenitor cells in FSL-1-treated NHP. Combining the efficacy of FSL-1 in promoting hematopoietic cell recovery with the lack of adverse effects induced by a single administration supports the application of FSL-1 as a viable countermeasure against H-ARS.
Topics: Humans; Mice; Animals; Toll-Like Receptor 2; Toll-Like Receptor 6; Ligands; Acute Radiation Syndrome; Primates; Fibroblasts
PubMed: 38051771
DOI: 10.1073/pnas.2122178120 -
Radiation Oncology Journal Sep 2014To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in... (Review)
Review
To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.
PubMed: 25324981
DOI: 10.3857/roj.2014.32.3.103 -
Frontiers in Pharmacology 2023Selenium (Se) has been reported to have an antagonistic effect on heavy metals in animals. Nevertheless, there is a lack of epidemiological research examining whether...
Moderate selenium mitigates hand grip strength impairment associated with elevated blood cadmium and lead levels in middle-aged and elderly individuals: insights from NHANES 2011-2014.
Selenium (Se) has been reported to have an antagonistic effect on heavy metals in animals. Nevertheless, there is a lack of epidemiological research examining whether Se can mitigate the adverse effects of cadmium (Cd) and lead (Pb) on hand grip strength (HGS) in middle-aged and elderly individuals. This study used data from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). HGS measurements were conducted by trained examiners with a dynamometer. Concentrations of Se, Cd, and Pb in blood were determined inductively coupled plasma mass spectrometry. We employed linear regression, restricted cubic splines, and quantile g-computation (qgcomp) to assess individual and combined associations between heavy metals and HGS. The study also explored the potential influence of Se on these associations. In both individual metal and multi-metal models adjusted for confounders, general linear regression showed Se's positive association with HGS, while Cd and Pb inversely related to it. At varying Se-Cd and Se-Pb concentrations, high Se relative to low Se can attenuate Cd and Pb's HGS impact. An inverted U-shaped correlation exists between Se and both maximum and combined HGS, with Se's benefit plateauing beyond approximately 200 μg/L. Stratified analysis by Se quartiles reveals Cd and Pb's adverse HGS effects diminishing as Se levels increase. Qgcomp regression analysis detected Se alleviating HGS damage from combined Cd and Pb exposure. Subsequent subgroup analyses identified the sensitivity of women, the elderly, and those at risk of diabetes to HGS impairment caused by heavy metals, with moderate Se supplementation beneficial in mitigating this effect. In the population at risk for diabetes, the protective role of Se against heavy metal toxicity-induced HGS reduction is inhibited, suggesting that diabetic individuals should particularly avoid heavy metal-induced handgrip impairment. Blood Cd and Pb levels are negatively correlated with HGS. Se can mitigate this negative impact, but its effectiveness plateaus beyond 200 μg/L. Women, the elderly, and those at risk of diabetes are more vulnerable to HGS damage from heavy metals. While Se supplementation can help, its protective effect is limited in high diabetes risk groups.
PubMed: 38161700
DOI: 10.3389/fphar.2023.1324583 -
Frontiers in Pharmacology 2021There are no FDA-approved drugs to mitigate the delayed effects of radiation exposure that may occur after a radiological attack or nuclear accident. To date,...
There are no FDA-approved drugs to mitigate the delayed effects of radiation exposure that may occur after a radiological attack or nuclear accident. To date, angiotensin-converting enzyme inhibitors are one of the most successful candidates for mitigation of hematopoietic, lung, kidney, and brain injuries in rodent models and may mitigate delayed radiation injuries after radiotherapy. Rat models of partial body irradiation sparing part of one hind leg (leg-out PBI) have been developed to simultaneously expose multiple organs to high doses of ionizing radiation and avoid lethal hematological toxicity to study the late effects of radiation. Exposures between 9 and 14 Gy damage the gut and bone marrow (acute radiation syndrome), followed by delayed injuries to the lung, heart, and kidney. The goal of the current study is to compare the pharmacokinetics (PK) of a lead angiotensin converting enzyme (ACE) inhibitor, lisinopril, in irradiated vs. nonirradiated rats, as a step toward licensure by the FDA. Female WAG/RijCmcr rats were irradiated with 12.5-13 Gy leg-out PBI. At day 35 after irradiation, during a latent period for injury, irradiated and nonirradiated siblings received a single gavage (0.3 mg, 0.6 mg) or intravenous injection (0.06 mg) of lisinopril. Plasma, urine, lung, liver and kidney levels of lisinopril were measured at different times. PK modeling (R package) was performed to track distribution of lisinopril in different compartments. A two-compartment (central plasma and periphery) PK model best fit lisinopril measurements, with two additional components, the gavage and urine. The absorption and renal clearance rates were similar between nonirradiated and irradiated animals (respectively: ratios 0.883, = 0.527; 0.943, = 0.605). Inter-compartmental clearance (from plasma to periphery) for the irradiated rats was lower than for the nonirradiated rats (ratio 0.615, = 0.003), while the bioavailability of the drug was 33% higher (ratio = 1.326, < 0.001). Since receptors for lisinopril are present in endothelial cells lining blood vessels, and radiation induces vascular regression, it is possible that less lisinopril remains bound in irradiated rats, increasing circulating levels of the drug. However, this study cannot rule out changes in total amount of lisinopril absorbed or excreted long-term, after irradiation in rats.
PubMed: 33986677
DOI: 10.3389/fphar.2021.646076 -
The Science of the Total Environment Jul 2022Crop residues are of crucial importance to maintain or even increase soil carbon stocks and fertility, and thereby to address the global challenge of climate change... (Meta-Analysis)
Meta-Analysis Review
Crop residues are of crucial importance to maintain or even increase soil carbon stocks and fertility, and thereby to address the global challenge of climate change mitigation. However, crop residues can also potentially stimulate emissions of the greenhouse gas nitrous oxide (NO) from soils. A better understanding of how to mitigate NO emissions due to crop residue management while promoting positive effects on soil carbon is needed to reconcile the opposing effects of crop residues on the greenhouse gas balance of agroecosystems. Here, we combine a literature review and a meta-analysis to identify and assess measures for mitigating NO emissions due to crop residue application to agricultural fields. Our study shows that crop residue removal, shallow incorporation, incorporation of residues with C:N ratio > 30 and avoiding incorporation of residues from crops terminated at an immature physiological stage, are measures leading to significantly lower NO emissions. Other practices such as incorporation timing and interactions with fertilisers are less conclusive. Several of the evaluated NO mitigation measures implied negative side-effects on yield, soil organic carbon storage, nitrate leaching and/or ammonia volatilization. We identified additional strategies with potential to reduce crop residue NO emissions without strong negative side-effects, which require further research. These are: a) treatment of crop residues before field application, e.g., conversion of residues into biochar or anaerobic digestate, b) co-application with nitrification inhibitors or N-immobilizing materials such as compost with a high C:N ratio, paper waste or sawdust, and c) use of residues obtained from crop mixtures. Our study provides a scientific basis to be developed over the coming years on how to increase the sustainability of agroecosystems though adequate crop residue management.
Topics: Agriculture; Carbon; Fertilizers; Greenhouse Gases; Nitrous Oxide; Soil
PubMed: 35276154
DOI: 10.1016/j.scitotenv.2022.154388 -
ACS Pharmacology & Translational Science Apr 2021Neuroinflammation contributes to delayed secondary cell death following traumatic brain injury (TBI), has the potential to chronically exacerbate the initial insult, and...
-Adamantyl Phthalimidine: A New Thalidomide-like Drug That Lacks Cereblon Binding and Mitigates Neuronal and Synaptic Loss, Neuroinflammation, and Behavioral Deficits in Traumatic Brain Injury and LPS Challenge.
Neuroinflammation contributes to delayed secondary cell death following traumatic brain injury (TBI), has the potential to chronically exacerbate the initial insult, and represents a therapeutic target that has largely failed to translate into human efficacy. Thalidomide-like drugs have effectively mitigated neuroinflammation across cellular and animal models of TBI and neurodegeneration but are complicated by adverse actions in humans. We hence developed -adamantyl phthalimidine (NAP) as a new thalidomide-like drug to mitigate inflammation without binding to cereblon, a key target associated with the antiproliferative, antiangiogenic, and teratogenic actions seen in this drug class. We utilized a phenotypic drug discovery approach that employed multiple cellular and animal models and ultimately examined immunohistochemical, biochemical, and behavioral measures following controlled cortical impact (CCI) TBI in mice. NAP mitigated LPS-induced inflammation across cellular and rodent models and reduced oligomeric α-synuclein and amyloid-β mediated inflammation. Following CCI TBI, NAP mitigated neuronal and synaptic loss, neuroinflammation, and behavioral deficits, and is unencumbered by cereblon binding, a key protein underpinning the teratogenic and adverse actions of thalidomide-like drugs in humans. In summary, NAP represents a new class of thalidomide-like drugs with anti-inflammatory actions for promising efficacy in the treatment of TBI and potentially longer-term neurodegenerative disorders.
PubMed: 33860215
DOI: 10.1021/acsptsci.1c00042 -
Healthcare (Basel, Switzerland) Apr 2020The objective of this review is to document contemporary barriers to accessing healthcare faced by Indigenous people of Canada and approaches taken to mitigate these... (Review)
Review
The objective of this review is to document contemporary barriers to accessing healthcare faced by Indigenous people of Canada and approaches taken to mitigate these concerns. A narrative review of the literature was conducted. Barriers to healthcare access and mitigating strategies were aligned into three categories: proximal, intermediate, and distal barriers. Proximal barriers include geography, education attainment, and negative bias among healthcare professionals resulting in a lack of or inadequate immediate care in Indigenous communities. Intermediate barriers comprise of employment and income inequities and health education systems that are not accessible to Indigenous people. Distal barriers include colonialism, racism and social exclusion, resulting in limited involvement of Indigenous people in policy making and planning to address community healthcare needs. Several mitigation strategies initiated across Canada to address the inequitable health concerns include allocation of financial support for infrastructure development in Indigenous communities, increases in Indigenous education and employment, development of culturally sensitive education and medical systems and involvement of Indigenous communities and elders in the policy-making system. Indigenous people in Canada face systemic/policy barriers to equitable healthcare access. Addressing these barriers by strengthening services and building capacity within communities while integrating input from Indigenous communities is essential to improve accessibility.
PubMed: 32357396
DOI: 10.3390/healthcare8020112 -
Annals of Work Exposures and Health Nov 2023When it comes to controlling workplace transmission of SARS-CoV-2, the virus that causes COVID-19, different workplaces and industrial sectors face different challenges,...
A deep dive into selected work sectors during the COVID-19 pandemic and the "living with COVID" phase: understanding similarities and differences in practice, perceptions, and preparedness.
OBJECTIVES
When it comes to controlling workplace transmission of SARS-CoV-2, the virus that causes COVID-19, different workplaces and industrial sectors face different challenges, both in terms of likely transmission routes and which control measures can be practically, economically, and effectively implemented. This article considers a large body of research in the United Kingdom across different work sectors and time points during the COVID-19 pandemic to better understand mitigation measures, challenges to mitigating the risk of SARS-COV-2 transmission, knowledge gaps, and barriers and enablers to control viral transmission.
METHODS
Data is drawn from 2 phases of research. Phase 1 gathered data from an interactive workshop (April 2022) where PROTECT researchers working across 8 work sectors shared knowledge and expertise from research conducted between 2020 and 2022. Phase 2 revisited 6 of these sectors to explore participants' views on the "living with COVID" phase of the pandemic (February-October 2022) through qualitative interviews.
RESULTS
Our findings emphasise the importance of considering the characteristics of each work sector (and their sub-sectors), relative to the physical workplace and workforce, the ways organisations operate, and how they interact with the public. Study findings show that participant's views and organisational practices changed quickly and significantly over the course of the pandemic. Most participants initially perceived that the majority of risk mitigations would remain in place for the foreseeable future. However, following the change in Government Guidance towards "living with COVID", most mitigation measures were quickly removed and it had become necessary for sectors/organisations to restore normal operations, thereby treating the COVID-19 virus like any other illness, while remaining prepared for future health emergencies that may arise.
CONCLUSION
We suggest that national policy makers and organisational leaders remain mindful of the lessons learned and knowledge gained at all levels (national, regional, local, organisational, and individual) during the COVID-19 pandemic. We make recommendations in support of recovery as sectors/organisations continue "living with COVID" and other respiratory diseases; balanced with longer term planning for the next public health crisis.
Topics: Humans; COVID-19; Pandemics; SARS-CoV-2; Occupational Exposure; Workplace
PubMed: 37742042
DOI: 10.1093/annweh/wxad053