Search

Objective. International Commission on Radiological Protection (ICRP) Task Group 113 is developing reference values of organ and effective dose coefficients (DCs) for radiography, fluoroscopy, and computed tomography imaging exams. In support of these efforts, our focus is on pediatric diagnostic fluoroscopy. Contrast agents used during clinical examinations are an important consideration of the work undertaken by the Task Group. This work demonstrates the importance of including organ contrast volume concentrations for the calculation of reference organ DCs in the voiding cystourethrogram (VCUG). Approach. The ICRP newborn and 15 year female reference phantoms were utilized within the Particle and Heavy Ion Transport code system for the calculation of organ DCs. A pediatric radiologist with over 30 years of clinical experience defined the imaging fields for a VCUG examination consistent with clinical practice. Of these, four imaging fields were selected for investigation. The transport simulations modeled an iodinated contrast solution similar to Bracco Group's 18% weight per volume, cystografin diatrizoate meglumine and typical bladder content was supplemented to make up the remainder volume. Iodinated contrast volumes of 0%, 25%, 50%, 75%, and 100% concentration by volume were modeled and associated DCs for in-field organs were computed. Main results. Organ DCs were calculated for the urinary bladder wall, colon wall, ovaries, and uterus for both female phantoms under irradiation geometries representative of a VCUG examination. Some organ DCs increased with iodine volume in the bladder and other organ DCs decreased as the iodine contrast volume completely filled the bladder (100%). Significance. The study results demonstrate for the newborn phantom percent differences in organ DCs varied between 0%-10% for the organs of interest, while they varied between 0%-22% in the 15 year phantom suggesting the importance of including contrast media in Monte Carlo radiation transport simulations of the VCUG examination., (© 2024 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Purpose: To summarize dose trends from 1980 to 2020 for 19,651 U.S. Radiologic Technologists who reported assisting with fluoroscopically guided interventional procedures (FGIPs), overall and by work history characteristics., Materials and Methods: A total of 762,310 annual personal dose equivalents at a 10-mm reference depth (doses) during 1980-2020 for 43,823 participants of the U.S. Radiologic Technologists (USRT) cohort who responded to work history questionnaires administered during 2012-2014 were summarized. This population included 19,651 technologists who reported assisting with FGIP (≥1 time per month for ≥12 consecutive months) at any time during the study period. Doses corresponding to assistance with FGIP were estimated in terms of proximity to patients, monthly procedure frequency, and procedure type. Box plots and summary statistics (eg, medians and percentiles) were used to describe annual doses and dose trends., Results: Median annual dose corresponding to assistance with FGIP was 0.65 mSv (interquartile range [IQR], 0.60-1.40 mSv; 95th percentile, 6.80). Higher occupational doses with wider variability were associated with close proximity to patients during assistance with FGIP (median, 1.20 mSv [IQR, 0.60-4.18 mSv]; 95th percentile, 12.66), performing ≥20 FGIPs per month (median, 0.75 mSv [IQR, 0.60-2.40 mSv]; 95th percentile, 9.44), and assisting with high-dose FGIP (median, 0.70 mSv [IQR, 0.60-1.90 mSv]; 95th percentile, 8.30)., Conclusions: Occupational doses corresponding to assistance with FGIP were generally low but varied with exposure frequency, procedure type, and proximity to patients. These results highlight the need for vigilant dose monitoring, radiation safety training, and proper protective equipment., (Published by Elsevier Inc.)

Abstract: The process to arrive at the radiation protection practices of today to protect workers, patients, and the public, including sensitive populations, has been a long and deliberative one. This paper presents an overview of the US Environmental Protection Agency's (US EPA) responsibility in protecting human health and the environment from unnecessary exposure to radiation. The origins of this responsibility can be traced back to early efforts, a century ago, to protect workers from x rays and radium. The system of radiation protection we employ today is robust and informed by the latest scientific consensus. It has helped reduce or eliminate unnecessary exposures to workers, patients, and the public while enabling the safe and beneficial uses of radiation and radioactive material in diverse areas such as energy, medicine, research, and space exploration. Periodic reviews and analyses of research on health effects of radiation by scientific bodies such as the National Academy of Sciences, National Council on Radiation Protection and Measurements, United Nations Scientific Committee on the Effects of Atomic Radiation, and the International Commission on Radiological Protection continue to inform radiation protection practices while new scientific information is gathered. As a public health agency, US EPA is keenly interested in research findings that can better elucidate the effects of exposure to low doses and low dose rates of radiation as applicable to protection of diverse populations from various sources of exposure. Professional organizations such as the Health Physics Society can provide radiation protection practitioners with continuing education programs on the state of the science and describe the key underpinnings of the system of radiological protection. Such efforts will help equip and prepare radiation protection professionals to more effectively communicate radiation health information with their stakeholders., (Copyright © 2024 Health Physics Society.)

Background: Many high-dose groups demonstrate increased leukaemia risks, with risk greatest following childhood exposure; risks at low/moderate doses are less clear., Methods: We conducted a pooled analysis of the major radiation-associated leukaemias (acute myeloid leukaemia (AML) with/without the inclusion of myelodysplastic syndrome (MDS), chronic myeloid leukaemia (CML), acute lymphoblastic leukaemia (ALL)) in ten childhood-exposed groups, including Japanese atomic bomb survivors, four therapeutically irradiated and five diagnostically exposed cohorts, a mixture of incidence and mortality data. Relative/absolute risk Poisson regression models were fitted., Results: Of 365 cases/deaths of leukaemias excluding chronic lymphocytic leukaemia, there were 272 AML/CML/ALL among 310,905 persons (7,641,362 person-years), with mean active bone marrow (ABM) dose of 0.11 Gy (range 0-5.95). We estimated significant (P < 0.005) linear excess relative risks/Gy (ERR/Gy) for: AML (n = 140) = 1.48 (95% CI 0.59-2.85), CML (n = 61) = 1.77 (95% CI 0.38-4.50), and ALL (n = 71) = 6.65 (95% CI 2.79-14.83). There is upward curvature in the dose response for ALL and AML over the full dose range, although at lower doses (<0.5 Gy) curvature for ALL is downwards., Discussion: We found increased ERR/Gy for all major types of radiation-associated leukaemia after childhood exposure to ABM doses that were predominantly (for 99%) <1 Gy, and consistent with our prior analysis focusing on <100 mGy., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Species boundaries are difficult to establish in groups with very similar morphology. As an alternative, it has been suggested to integrate multiple sources of data to clarify taxonomic problems in taxa where cryptic speciation processes have been reported. This is the case of the harvest mouse Reithrodontomys mexicanus , which has a problematic taxonomy history as it is considered a complex species. Here, we evaluate the cryptic diversity of R. mexicanus using an integrative taxonomy approach in order to detect candidate lineages at the species level. The molecular analysis used one mitochondrial ( cytb ) and two nuclear ( Fgb-I7 and IRBP ) genes. Species hypotheses were suggested based on three molecular delimitation methods (mPTP, bGMYC, and STACEY) and cytb genetic distance values. Skull and environmental space differences between the delimited species were also tested to complement the discrimination of candidate species. Based on the consensus across the delimitation methods and genetic distance values, four species were proposed, which were mostly supported by morphometric and ecological data: R. mexicanus clade I, R. mexicanus clade IIA, R. mexicanus clade IIIA, and R. mexicanus clade IIIB. In addition, the evolutionary relationships between the species that comprise the R. mexicanus group were discussed from a phylogenetic approach. Our findings present important taxonomic implications for Reithrodontomys , as the number of known species for this genus increases. Furthermore, we highlight the importance of the use of multiple sources of data in systematic studies to establish robust delimitations between species considered taxonomically complex., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: In ISCHEMIA-CKD, 777 patients with advanced chronic kidney disease and chronic coronary disease had similar all-cause mortality with either an initial invasive or conservative strategy (27.2% vs 27.8%, respectively)., Objectives: This prespecified secondary analysis from ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease) was conducted to determine whether an initial invasive strategy compared with a conservative strategy decreased the incidence of cardiovascular (CV) vs non-CV causes of death., Methods: Three-year cumulative incidences were calculated for the adjudicated cause of death. Overall and cause-specific death by treatment strategy were analyzed using Cox models adjusted for baseline covariates. The association between cause of death, risk factors, and treatment strategy were identified., Results: A total of 192 of the 777 participants died during follow-up, including 94 (12.1%) of a CV cause, 59 (7.6%) of a non-CV cause, and 39 (5.0%) of an undetermined cause. The 3-year cumulative rates of CV death were similar between the invasive and conservative strategies (14.6% vs 12.6%, respectively; HR: 1.13, 95% CI: 0.75-1.70). Non-CV death rates were also similar between the invasive and conservative arms (8.4% and 8.2%, respectively; HR: 1.25; 95% CI: 0.75-2.09). Sudden cardiac death (46.8% of CV deaths) and infection (54.2% of non-CV deaths) were the most common cause-specific deaths and did not vary by treatment strategy., Conclusions: In ISCHEMIA-CKD, CV death was more common than non-CV or undetermined death during the 3-year follow-up. The randomized treatment assignment did not affect the cause-specific incidences of death in participants with advanced CKD and moderate or severe myocardial ischemia. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease [ISCHEMIA-CKD]; NCT01985360)., Competing Interests: Funding Support and Author Disclosures This project was supported by grants from the National Institutes of Health grants U01H117904 and U01HL117905; Arbor Pharmaceuticals, LLC; and AstraZeneca Pharmaceuticals, LP. Devices or medications were provided by Abbott Vascular (previously St. Jude Medical, Inc); Medtronic, Inc; Phillips (previously Volcano Corporation); Omron Healthcare, Inc; Arbor Pharmaceuticals, LLC; AstraZeneca Pharmaceuticals, LP; Espero Pharmaceuticals; Merck Sharp and Dohme Corp; and Sunovion Pharmaceuticals. The manuscript contents are solely the responsibility of the authors and do not necessarily represent official views of the National Heart, Lung, and Blood Institute, the National Institutes of Health, or the United States Department of Health and Human Services. Dr Sidhu has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; and has received personal fees from AstraZeneca and Sanofi-Regeneron outside the submitted work. Dr Alexander has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Mr Huang has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Mathew has received grants from National Heart, Lung, and Blood Institute, during the conduct of the study. Dr Newman has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr O’Brien has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Pellikka has received grants from National Heart, Lung, and Blood Institute during the conduct of the study. Dr Bockeria has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Briguori has received grants from the National Heart, Lung, and Blood Institute, during the conduct of the study. Dr Kretov has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Mazurek has received grants from the National Heart, Lung, and Blood Institute, during the conduct of the study. Dr Orso has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Roik has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Sajeev has received grants from National Heart, Lung, and Blood Institute, during the conduct of the study. Dr Shutov has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Rockhold reports grants from the National Institutes of Health, the Patient-Centered Outcomes Research Institute, Bristol Myers Squibb, AstraZeneca, American Regent, Gates Foundation, and Eidos during the conduct of the study; has received consulting fees from Janssen, Clover, Doctor Evidence, and Intercept; and equity ownership in GlaxoSmithKline, Clover, Athira, Doctor Evidence, DataVant, Spencer Health Solutions, and Adaptic Health. Dr Borrego has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Balter has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Stone has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; has received speaker honoraria from Pulnovo and Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Vascular Dynamics, Shockwave, V-Wave, Cardiomech, Gore, and Amgen; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. Dr Stone’s daughter is an employee at Medtronic. Dr Stone’s employer, Mount Sinai Hospital, receives research support from Abbott, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, and V-wave. Dr Chaitman has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; and has received personal fees from Merck, NovoNordisk, Sanofi, Lilly, Johnson and Johnson, Daiichi Sankyo, Tricida, Relypsa, Imbria, and Xylocor outside the submitted work. Dr Goodman has received grants and personal fees from the National Heart, Lung, and Blood Institute during the conduct of the study; has received grants and personal fees from Amgen; AstraZeneca, Bayer, Boehringer Ingelheim/Eli Lilly, Bristol Myers Squibb/Pfizer, CSL Behring/PERFUSE, Daiichi Sankyo/American Regent/DCRI, Ferring, Novartis, and Regeneron/Sanofi; and has received personal fees from Esperion/C5, GlaxoSmithKline, HLS Therapeutics, Merck, NovoNordisk, and Servier outside the submitted work. Dr Fleg has reports employment by the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Reynolds has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; and has received nonfinancial support from Abbott Vascular, Siemens, and BioTelemetry outside the submitted work. Dr Maron has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Hochman is the principal investigator for the ISCHEMIA trial for which, in addition to support by the National Heart, Lung, and Blood Institute grant, devices and medications were provided by Abbott Vascular; Medtronic, Inc; Abbott Laboratories (formerly St. Jude Medical, Inc); Royal Philips NV (formerly Volcano Corporation); Arbor Pharmaceuticals, LLC; AstraZeneca Pharmaceuticals, LP; Merck Sharp and Dohme Corp; Omron Healthcare, Inc, Sunovion Pharmaceuticals, Inc Espero BioPharma; and Amgen, Inc; and has received financial donations from Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP. Dr Bangalore has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; has received grants and personal fees from Abbott Vascular; and has received personal fees from Biotronik, Pfizer, Amgen, and Reata outside the submitted work. Dr Lyubarova has reported that she has no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. All rights reserved.)

Human immunodeficiency virus (HIV) reverse transcriptase (RT)-associated ribonuclease H (RNase H) remains as the only enzyme encoded within the viral genome not clinically validated as an antiviral target. We have previously reported that the galloyl derivative II-25 had RNase H inhibitory activity in enzymatic assays but showed weak antiviral activity in phenotypic assays due its large polarity and poor membrane permeability. In this report, we report on a series of II-25 derivatives, obtained by addition of different hydrophobic moieties ("the wings") at the C-2 and C-3 positions of the piperazine ring that showed improved RNase H inhibitory activity. Six compounds showed strong inhibitory activity and were found to be more potent than β-thujaplicinol in enzymatic assays. The most potent compound was IA-6 and exhibited the best inhibitory activity (IC 50  = 0.067 ± 0.02 μM). IA-6 was around 11 and 30 times more potent than II-25 and β-thujaplicinol, respectively. Molecular modeling studies predict a strong hydrophobic interaction between the furylmethylaminyl group of IA-6 and the side chain of His539, explaining the potent HIV-1 RNase H inhibition. Unfortunately, none of the derivatives showed significant antiviral activity in cell culture. It is worth emphasizing that most of the obtained compounds show low cytotoxicity (CC 50  > 20 μM), which confirms the significance of identifying galloyl derivatives as valuable leads for further optimization., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial demonstrated no overall difference in the composite primary endpoint and the secondary endpoints of cardiovascular (CV) death/myocardial infarction or all-cause mortality between an initial invasive or conservative strategy among participants with chronic coronary disease and moderate or severe myocardial ischemia. Detailed cause-specific death analyses have not been reported., Methods: We compared overall and cause-specific death rates by treatment group using Cox models with adjustment for pre-specified baseline covariates. Cause of death was adjudicated by an independent Clinical Events Committee as CV, non-CV, and undetermined. We evaluated the association of risk factors and treatment strategy with cause of death., Results: Four-year cumulative incidence rates for CV death were similar between invasive and conservative strategies (2.6% vs 3.0%; hazard ratio [HR] 0.98; 95% CI [0.70-1.38]), but non-CV death rates were higher in the invasive strategy (3.3% vs 2.1%; HR 1.45 [1.00-2.09]). Overall, 13% of deaths were attributed to undetermined causes (38/289). Fewer undetermined deaths (0.6% vs 1.3%; HR 0.48 [0.24-0.95]) and more malignancy deaths (2.0% vs 0.8%; HR 2.11 [1.23-3.60]) occurred in the invasive strategy than in the conservative strategy., Conclusions: In International Study of Comparative Health Effectiveness with Medical and Invasive Approaches, all-cause and CV death rates were similar between treatment strategies. The observation of fewer undetermined deaths and more malignancy deaths in the invasive strategy remains unexplained. These findings should be interpreted with caution in the context of prior studies and the overall trial results., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: To describe the range of occupational badge dose readings and annualized dose records among physicians performing fluoroscopically guided interventional (FGI) procedures using job title information provided by the same 3 major medical institutions in 2009, 2012, and 2015., Materials and Methods: The Radiation Safety Office of selected hospitals was contacted to request assistance with identifying physicians in a large commercial dosimetry database. All entries judged to be uninformative of occupational doses to FGI procedure staff were excluded. Monthly and annualized doses were described with univariate statistics and box-and-whisker plots., Results: The dosimetry data set of interventional radiology staff contained 169 annual dose records from 77 different physicians and 698 annual dose records from 455 nonphysicians. The median annualized lens dose equivalent values among physicians (11.9 mSv; interquartile range [IQR], 6.9-20.0 mSv) was nearly 3-fold higher than those among nonphysician medical staff assisting with FGI procedures (4.0 mSv; IQR, 1.8-6.7 mSv) (P < .001). During the study period, without eye protection, 25% (23 of 93) of the physician annualized lens dose equivalent values may have exceeded 20 mSv; for nonphysician medical staff, this value may have been exceeded 3.5% (6 of 173) of the time. However, these values did not account for eye protection., Conclusions: The findings from this study highlight the importance of mitigating occupational dose to the eyes of medical staff, particularly physicians, performing or assisting with FGI procedures. Training on radiation protection principles, the use of personal protective equipment, and patient radiation dose management can all help ensure that the occupational radiation dose is adequately controlled., (Copyright © 2021. Published by Elsevier Inc.)

Optogenetics is a modern technique which has been recently expanded to non-neuronal cell types, e.g., astrocytes, and involves targeted gene delivery of light-sensitive ion channels like Channelrhodopsin-2 (ChR2). Optogenetic regulation of astrocytic activity can be used for therapeutic intervention of several neurological disorders. Astrocytic gene delivery, viz adeno-associated viral (AAV) vectors, have proven to be robust, time-, and cost-efficient contrary to the generation of transgenic animal models. When transducing astrocytes with an AAV vector, it is imperative to perform a serotype evaluation of the AAV vector due to variability in serotype transduction efficiency depending on species, target region and construct length. Rats have been a very successful animal model for studying a variety of brain disorders, from which ChR2-based intervention of astrocytes will benefit. However, the most efficient AAV capsid serotype targeting astrocytes for ChR2 expression in the in vivo rat brain cortex has not been characterized. To address this, we have evaluated AAV serotypes 1, 5, and 8 of the vector AAV-GFAP-hChR2(H134)-mCherry targeting astrocytes in the rat brain neocortex. Results show that serotype 8 exhibits promising transduction patterns, as it has demonstrated the highest tangential and radial viral spread in the rat brain. Our research will facilitate translational research for future applications of optogenetics involving the transduction of rat brain cortical astrocytes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The Reithrodontomys tenuirostris species group is considered "the most specialized" within the genus Reithrodontomys from morphological and ecological perspectives. Previous studies based on molecular data recommended changes in the taxonomy of the group. In particular, R. microdon has been the most taxonomically questioned, with the suggestion that it constitutes a complex of cryptic species. We analyzed the phylogenetic relationships of the R. tenuirostris species group using DNA sequences from the mitochondrial Cytochrome b gene and Intron 7 of the nuclear beta fibrinogen gene. In addition, divergence times were estimated, and possible new taxa delimited with three widely used species delimitation methods. Finally, possible connectivity routes based on shared haplotypes were tested among the R. microdon populations. All species were recovered as monophyletic with the exception of R. microdon , whose individuals were grouped into four different haplogroups, one of which included specimens of R. bakeri . Diversification within the R. tenuirostris species group began about 3 Ma, in the Pleistocene. The bGMYC and STACEY delimitation methods were congruent with each other, delimiting at the species-level each haplogroup within R. microdon , while the mPTP suggested a greater number of species. Moreover, none of the haplogroups showed potential connectivity routes between them, evidencing lack of gene flow. Our results suggest the existence of a higher number of species in the R. tenuirostris group, because we show that there are four species within what is currently recognized as R. microdon ., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Mammalogists.)

There is limited evidence that non-leukaemic lymphoid malignancies are radiogenic. As radiation-related cancer risks are generally higher after childhood exposure, we analysed pooled lymphoid neoplasm data in nine cohorts first exposed to external radiation aged <21 years using active bone marrow (ABM) and, where available, lymphoid system doses, and harmonised outcome classification. Relative and absolute risk models were fitted. Years of entry spanned 1916-1981. At the end of follow-up (mean 42.1 years) there were 593 lymphoma (422 non-Hodgkin (NHL), 107 Hodgkin (HL), 64 uncertain subtype), 66 chronic lymphocytic leukaemia (CLL) and 122 multiple myeloma (MM) deaths and incident cases among 143,136 persons, with mean ABM dose 0.14 Gy (range 0-5.95 Gy) and mean age at first exposure 6.93 years. Excess relative risk (ERR) was not significantly increased for lymphoma (ERR/Gy = -0.001; 95% CI: -0.255, 0.279), HL (ERR/Gy = -0.113; 95% CI: -0.669, 0.709), NHL + CLL (ERR/Gy = 0.099; 95% CI: -0.149, 0.433), NHL (ERR/Gy = 0.068; 95% CI: -0.253, 0.421), CLL (ERR/Gy = 0.320; 95% CI: -0.678, 1.712), or MM (ERR/Gy = 0.149; 95% CI: -0.513, 1.063) (all p-trend > 0.4). In six cohorts with estimates of lymphatic tissue dose, borderline significant increased risks (p-trend = 0.02-0.07) were observed for NHL + CLL, NHL, and CLL. Further pooled epidemiological studies are needed with longer follow-up, central outcome review by expert hematopathologists, and assessment of radiation doses to lymphoid tissues., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)