David J. Brenner's research while affiliated with Columbia University and other places

Publications (614)

Article
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A large-scale malicious or accidental radiological event can expose vast numbers of people to ionizing radiation. The dicentric chromosome (DCA) and cytokinesis-block micronucleus (CBMN) assays are well-established biodosimetry methods for estimating individual absorbed doses after radiation exposure. Here we used machine learning (ML) to test the...
Article
Far UVC light (UVC wavelengths below 235 nm) is a comparatively new modality with significant potential to safely and very efficiently inactivate airborne pathogens in occupied indoor locations. There are now significant accumulations of evidence both in terms of the safety of far‐UVC for direct exposure of occupied indoor locations, and in terms o...
Preprint
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Background: Non-human primates, such as Rhesus macaques, are a powerful model for studies of the cellular and physiological effects of radiation, development of radiation biodosimetry, and for understanding the impact of radiation on human health. Here, we study the effects of 4 Gy total body irradiation (TBI) at the molecular level out to 28 days...
Article
Far‐UVC radiation, defined in this paper as ultraviolet (UV) radiation with wavelengths from 200 nm – 235 nm, is a promising tool to help prevent the spread of disease. The unique advantage of far‐UVC technology over traditional UV germicidal irradiation lies in the potential for direct application of far‐UVC into occupied spaces since antimicrobia...
Article
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Far UV-C, informally defined as electromagnetic radiation with wavelengths between 200 and 230 nm, has characteristics that are well-suited to control of airborne pathogens. Specifically, Far UV-C has been shown to be highly effective for inactivation of airborne pathogens; yet this same radiation has minimal potential to cause damage to human skin...
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High-throughput biodosimetry methods to determine exposure to ionizing radiation (IR) that can also be easily scaled to multiple testing sites in emergency situations are needed in the event of malicious attacks or nuclear accidents that may involve a substantial number of civilians. In the event of an improvised nuclear device (IND), a complex IR...
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Biological materials can be shipped off-site for diagnostic, therapeutic and research purposes. They usually are kept in certain environments for their final application during transportation. However, active reagent handling during transportation from a collection site to a laboratory or biorepository has not been reported yet. In this paper, we s...
Preprint
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Far-UVC radiation, commonly defined as wavelengths from 200 nm – 235 nm, is a promising tool to help prevent the spread of disease. The unique advantage of far-UVC technology over traditional ultraviolet germicidal irradiation lies in the potential for direct application of far-UVC into occupied spaces since antimicrobial doses of far-UVC are signi...
Article
Far‐UVC radiation, typically defined as 200‐235 nm, has similar or greater anti‐microbial efficacy compared to conventional 254‐nm germicidal radiation. In addition, biophysical considerations of the interaction of far‐UVC with tissue, as well as multiple short‐term safety studies in animal models and humans, suggest that far‐UVC exposure may be sa...
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Recent research using UV radiation with wavelengths in the 200–235 nm range, often referred to as far-UVC, suggests that the minimal health hazard associated with these wavelengths will allow direct use of far-UVC radiation within occupied indoor spaces to provide continuous disinfection. Earlier experimental studies estimated the susceptibility of...
Article
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Many infectious diseases, including COVID-19, are transmitted by airborne pathogens. There is a need for effective environmental control measures which, ideally, are not reliant on human behaviour. One potential solution is Krypton Chloride (KrCl) excimer lamps (often referred to as Far-UVC), which can efficiently inactivate pathogens, such as coro...
Preprint
Full-text available
Far-UVC radiation, typically defined as 200-235 nm, has similar or greater anti-microbial efficacy compared to conventional 254-nm germicidal radiation. In addition, biophysical considerations of the interaction of far-UVC with tissue, as well as multiple short-term safety studies in animal models and humans, suggest that far-UVC exposure may be sa...
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DNA repair phenotype can be measured in blood and may be a potential biomarker of cancer risk. We conducted a systematic review and meta-analysis of epidemiological studies of DNA repair phenotype and cancer through March 2021. We used random-effects models to calculate pooled odds ratios (ORs) of cancer risk for those with the lowest DNA repair ca...
Article
Standard dosimetry protocols exist for highly penetrating photon and particle beams used in the clinic and in research. However, these protocols cannot be directly applied to shallow penetration MeV-range ion beams. The Radiological Research Accelerator Facility has been using such beams for almost 50 years to irradiate cell monolayers, using self-...
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The effectiveness of UVC to reduce airborne‐mediated disease transmission is well‐established. However conventional germicidal UVC (~254 nm) cannot be used directly in occupied spaces because of the potential for damage to the skin and eye. A recently studied alternative with the potential to be used directly in occupied spaces is far‐UVC (200 to 2...
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The space radiation environment is qualitatively different from Earth, and its radiation hazard is generally quantified relative to photons using quality factors that allow assessment of biologically-effective dose. Two approaches exist for estimating radiation quality factors in complex low/intermediate-dose radiation environments: one is a fluenc...
Preprint
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Purpose It has been suggested that heavy-ion radiation therapy may contribute to the control of distal metastases. These distant responses may include immune cell activation. Immunostimulation resulting from radiation-induced immunogenic cell death (ICD) of cancer cells, leads to the recruitment of anti-tumor T cells. Specific markers of ICD includ...
Preprint
Standard dosimetry protocols exist for highly penetrating photon and particle beams used in the clinic and in research. However, these protocols cannot be directly applied to shallow penetration MeV-range ion beams. The Radiological Research Accelerator Facility has been using such beams for almost 50 years to irradiate cell monolayers, using self-...
Preprint
Full-text available
The Radiological Research Accelerator Facility has modified a decommissioned Varian Clinac to deliver FLASH dose rates: Operating in 9 MeV electron mode (FLASH mode), samples can be irradiated inside the Clinac head at average dose rates of up to 600 Gy/sec (3 Gy per 0.5 µsec pulse, 180 pulses per sec). In this mode multiple pulses are required for...
Preprint
Full-text available
The effectiveness of UVC to reduce airborne-mediated disease transmission is well-established. However conventional germicidal UVC (~254 nm) cannot be used directly in occupied spaces because of the potential for damage to the skin and eye. A recently studied alternative with the potential to be used directly in occupied spaces is far-UVC (200 to 2...
Article
Full-text available
Ionizing radiations encountered by astronauts on deep space missions produce biological damage by two main mechanisms: (1) Targeted effects (TE) due to direct traversals of cells by ionizing tracks. (2) Non-targeted effects (NTE) caused by release of signals from directly hit cells. The combination of these mechanisms generates non-linear dose resp...
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Transmission of SARS-CoV-2 by aerosols has played a significant role in the rapid spread of COVID-19 across the globe. Indoor environments with inadequate ventilation pose a serious infection risk. Whilst vaccines suppress transmission, they are not 100% effective and the risk from variants and new viruses always remains. Consequently, many efforts...
Preprint
Full-text available
Many infectious diseases, including COVID-19, are transmitted by airborne pathogens. There is a need for effective environmental control measures which, ideally, are not reliant on human behaviour. One potential solution is Far-UVC which can efficiently inactivate pathogens, such as coronaviruses and influenza, in air. When appropriately filtered,...
Article
In a large-scale catastrophe, such as a nuclear detonation in a major city, it will be crucial to accurately diagnose large numbers of people to direct scarce medical resources to those in greatest need. Currently no FDA-cleared tests are available to diagnose radiation exposures, which can lead to complex, life-threatening injuries. To address thi...
Preprint
Full-text available
Ionizing radiations encountered by astronauts on deep space missions produce biological damage by two main mechanisms: (1) Targeted effects (TE) due to direct traversals of cells by ionizing tracks. (2) Non-targeted effects (NTE) caused by release of signals from directly hit cells. The combination of these mechanisms generates non-linear dose resp...
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Full-text available
Detonation of an improvised nuclear device highlights the need to understand the risk of mixed radiation exposure as prompt radiation exposure could produce significant neutron and gamma exposures. Although the neutron component may be a relatively small percentage of the total absorbed dose, the large relative biological effectiveness (RBE) can in...
Preprint
Full-text available
DNA repair phenotype can be measured in blood and may be a potential biomarker of cancer risk. We conducted a systematic review and meta-analysis of epidemiological studies of DNA repair phenotype and cancer through March 2021. We used random-effects models to calculate pooled odds ratios (ORs) of cancer risk for those with the lowest DNA repair ca...
Preprint
Full-text available
The space radiation environment is qualitatively different from Earth, and its radiation hazard is generally quantified relative to photons using quality factors that allow assessment of biologically-effective dose. Two approaches exist for estimating radiation quality factors in complex radiation environments: One is a fluence-based risk cross-sec...
Article
Full-text available
We report a shipping container that enables a disruptive logistics for cytogenetic biodosimetry for radiation countermeasures through pre-processing cell culture during transportation. The container showed precise temperature control (< 0.01 °C) with uniform sample temperature (< 0.1 °C) to meet the biodosimetry assay requirements. Using an existin...
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Radiation-induced cognitive dysfunction is increasingly recognized as an important risk for human exploration of distant planets. Mechanistically-motivated mathematical modeling helps to interpret and quantify this phenomenon. Here we considered two general mechanisms of ionizing radiation-induced damage: targeted effects (TE), caused by traversal...
Article
Mass casualty exposure scenarios from an improvised nuclear device are expected to be far more complex than simple photons. Based on the proximity to the explosion and potential shielding, a mixed field of neutrons and photons comprised of up to approximately 30% neutrons of the total dose is anticipated. This presents significant challenges for bi...
Article
During space missions, astronauts experience acute and chronic low-dose-rate radiation exposures. Given the clear gap of knowledge regarding such exposures, we assessed the effects acute and chronic exposure to a mixed field of neutrons and photons and single or fractionated simulated galactic cosmic ray exposure (GCRsim) on behavioral and cognitiv...
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Purpose The respiratory disease COVID-19 reached global pandemic status in 2020. Excessive inflammation is believed to result in the most severe symptoms and death from this disease. Since treatment options for patients with severe COVID-19 related pulmonary symptoms remain limited, whole-lung low-dose radiotherapy is being evaluated as an anti-inf...
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Stress response signals can propagate between cells damaged by targeted effects (TE) of ionizing radiation (e.g. energy depositions and ionizations in the nucleus) and undamaged “bystander” cells, sometimes over long distances. Their consequences, called non-targeted effects (NTE), can substantially contribute to radiation-induced damage (e.g. cell...
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We implemented machine learning in the radiation biodosimetry field to quantitatively reconstruct neutron doses in mixed neutron + photon exposures, which are expected in improvised nuclear device detonations. Such individualized reconstructions are crucial for triage and treatment because neutrons are more biologically damaging than photons. We us...
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Importance The coronavirus disease 2019 (COVID-19) pandemic has led to treatment delays for many patients with cancer. While published guidelines provide suggestions on which cases are appropriate for treatment delay, there are no good quantitative estimates on the association of delays with tumor control or risk of new metastases. Objectives To d...
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Far‐UVC radiation is a promising technology that is potentially both effective at killing airborne microbes such as coronaviruses and influenza, and being minimally hazardous to the skin and eyes. Our previous studies on health risks from far‐UVC have employed a krypton‐chloride (KrCl) excimer lamp, emitting principally at 222 nm, supplemented with...
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Quantitative mechanistic modeling of the biological effects of ionizing radiation has a long rich history. Initially, it was dominated by target theory, which quantifies damage caused by traversal of cellular targets like DNA by ionizing tracks. The discovery that mutagenesis, death and/or altered behavior sometimes occur in cells that were not the...
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There is growing interest in far‐UVC lighting, defined as wavelengths from 200 to 230 nm, because research has demonstrated these wavelengths to be an effective antimicrobial technology while posing a minimal hazard to human health. Far‐UVC lighting is now being installed to directly irradiate spaces where humans are present, and it will be importa...
Preprint
Full-text available
Radiation-induced cognitive dysfunction is increasingly recognized as an important risk for human exploration of distant planets. Mechanistically-motivated mathematical modeling helps to interpret and quantify this phenomenon. Here we considered two general mechanisms of ionizing radiation-induced damage: targeted effects (TE), caused by traversal...
Article
Inhalation and ingestion of 137Cs and other long-lived radionuclides can occur after large-scale accidental or malicious radioactive contamination incidents, resulting in a complex temporal pattern of radiation dose/dose rate, influenced by radionuclide pharmacokinetics and chemical properties. High-throughput radiation biodosimetry techniques for...
Article
An automated platform for cytogenetic biodosimetry, the "Rapid Automated Biodosimetry Tool II (RABiT-II)," adapts the dicentric chromosome assay (DCA) for high-throughput mass-screening of the population after a large-scale radiological event. To validate this test, the U.S. Federal Drug Administration (FDA) recommends demonstrating that the high-t...
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Limited availability of proton irradiators optimized for high-dose-rate studies makes the preclinical research of proton FLASH therapy challenging. We assembled two proton irradiation platforms that are capable of delivering therapeutic doses to thin biological samples at dose rates equal to and above 100 Gy/s. We optimized and tested dosimetry pro...
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This work aims to investigate far-UVC light at 222 nm as a new microbial reduction tool for planetary protection purposes which could potentially be integrated into the spacecraft assembly process. The major advantage of far-UVC (222 nm) compared to traditional germicidal UVC (254 nm) is the potential for application throughout the spacecraft assem...
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Following a large-scale radiological incident, there is a need for FDA-approved biodosimetry devices and biomarkers with the ability to rapidly determine past radiation exposure with sufficient accuracy for early population triage and medical management. Towards this goal, we have developed FAST-DOSE (Fluorescent Automated Screening Tool for Dosime...
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A direct approach to limit airborne viral transmissions is to inactivate them within a short time of their production. Germicidal ultraviolet light, typically at 254 nm, is effective in this context but, used directly, can be a health hazard to skin and eyes. By contrast, far-UVC light (207–222 nm) efficiently kills pathogens potentially without ha...
Preprint
Full-text available
A direct approach to limit airborne transmission of pathogens is to inactivate them within a short time of their production. Germicidal ultraviolet light (UV), typically at 254 nm, is effective in this context, but it is a health hazard to the skin and eyes. By contrast, far-UVC light (207-222 nm) efficiently kills pathogens without harm to exposed...
Article
Full-text available
Dosimetry is an important tool for triage and treatment planning following any radiation exposure accident, and biological dosimetry, which estimates exposure dose using a biological parameter, is a practical means of determining the specific dose an individual receives. The cytokinesis-blocked micronucleus assay (CBMN) is an established biodosimet...
Article
Full-text available
Environmental contamination and ingestion of the radionuclide Cesium-137 (¹³⁷Cs) is a large concern in fallout from a nuclear reactor accident or improvised nuclear device, and highlights the need to develop biological assays for low-dose rate, internal emitter radiation. To mimic low-dose rates attributable to fallout, we have developed a VAriable...
Article
Full-text available
Biodosimetry-based individualized reconstruction of complex irradiation scenarios (partial-body shielding and/or neutron + photon mixtures) can improve treatment decisions after mass-casualty radiation-related incidents. We used a high-throughput micronucleus assay with automated scanning and imaging software on ex-vivo irradiated human lymphocytes...
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Purpose: Exposure to ionizing radiation increases risk of breast cancer. Although proton radiation is encountered in outer space and in medicine, we do not fully understand breast cancer risks from protons due to limited in vivo data. The purpose of this study was to comparatively assess the effects of γ-rays and protons on mammary tumorigenesis i...
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The cytokinesis-block micronucleus (CBMN) assay is considered to be the most suitable biodosimetry method for automation. Previously, we automated this assay on a commercial robotic biotech high-throughput system (RABiT-II) adopting both a traditional and an accelerated micronucleus protocol, using centrifugation steps for both lymphocyte harvestin...
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In the event of a nuclear attack or large-scale radiation event, there would be an urgent need for assessing the dose to which hundreds or thousands of individuals were exposed. Biodosimetry approaches are being developed to address this need, including transcriptomics. Studies have identified many genes with potential for biodosimetry, but, to dat...
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We report the development of system for packaging critical components of the traditional collection kit to make an integrated fingerstick blood collector for self-collecting blood samples of 100 μl or more for radiation countermeasures. A miniaturized vacuum tube system (VacuStor system) has been developed to facilitate liquid reagent storage, simp...
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The consideration of how a given technique affects results of experimental measurements is a must to achieve correct data interpretation. This might be challenging when it comes to measurements on biological systems, where it is unrealistic to have full control (e.g. through a software replica) of all steps in the measurement chain. In this work we...
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Background: Measurement of γ-H2AX foci levels in cells provides a sensitive and reliable method for quantitation of the radiation-induced DNA damage response. The objective of the present study was to develop a rapid, high-throughput γ-H2AX assay based on imaging flow cytometry (IFC) using the ImageStream®X Mk II (ISX) platform to evaluate DNA dou...
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Accuracy and precision in dosimetry is crucial in studies involving animal models. Small animal dosimetry, in particular for protracted exposures to non uniform radiation fields is particularly challanging. We have developed a novel in-vivo dosimeter based on glass encapsulated TLD rods. These encapsulated rods can be injected into mice and used fo...
Article
We developed a fully-automated dicentric chromosome assay (DCA) in multiwell plates. All operations, from sample loading to chromosome scoring, are performed, without human intervention, by the second-generation Rapid Automated Biodosimetry Tool II (RABiT-II) robotic system, a plate imager and custom software, FluorQuantDic. The system requires sma...
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Full-text available
Background: Cesium-137 (137Cs) is one of the major and most clinically relevant radionuclides of concern in a radiological dispersal device, "dirty bomb" scenario as well as in nuclear accidents and detonations. In this exposure scenario, a significant amount of soluble radionuclide(s) may be dispersed into the atmosphere as a component of fallout...
Preprint
Environmental contamination and ingestion of the radionuclide Cesium-137 (137Cs) is a large concern in fallout from a nuclear reactor accident and improvised nuclear device and highlights the need to develop biological assays for low dose rate, internal emitter radiation. To mimic low dose rates attributable to fallout, we have developed a VAriable...
Preprint
Full-text available
Biodosimetry-based discrimination between homogeneous total-body photon exposure and complex irradiation scenarios (partial-body shielding and/or neutron + photon mixtures) can improve treatment decisions after mass-casualty radiation-related incidents. Our study objective was to use high-throughput biomarkers to: a) detect partial-body and/or neut...
Preprint
Full-text available
Dosimetry is an important tool for triage and treatment planning following any radiation exposure accident, and biological dosimetry, which estimates exposure dose using a biological parameter, is a practical means of determining the specific dose an individual receives. The cytokinesis-blocked micronucleus assay (CBMN) is an established biodosimet...
Preprint
In the event of a nuclear attack or radiation event, there would be an urgent need for assessing and reconstructing the dose to which hundreds or thousands of individuals were exposed. These measurements would need a rapid assay to facilitate triage and medical management for individuals based on dose. Our approaches to development of rapid assays...
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