Electromagnetic Exposure of Personnel Involved in Cardiac MRI Examinations in 1.5T, 3T and 7T Scanners

(1) Background: It has been hypothesised that a significant increase in the use of cardiac magnetic resonance (CMR), for example, when examining COVID-19 convalescents using magnetic resonance imaging (MRI), has an influence the exposure profiles of medical personnel to static magnetic fields (STmf). (2) Methods: Static exposure to STmf (SEmf) was recorded during activities that modelled performing CMR by radiographers. The motion-induced time variability of that exposure (TVEmf) was calculated from SEmf samples. The results were compared with: (i) labour law requirements; (ii) the distribution of vertigo perception probability near MRI magnets; and (iii) the exposure profile when actually performing a head MRI. (3) Results: The exposure profiles of personnel managing 42 CMR scans (modelled using medium (1.5T), high (3T) and ultrahigh (7T) field scanners) were significantly different than when managing a head MRI. The majority of SEmf and TVEmf samples (up to the 95th percentile) were at low vertigo perception probability (SEmf < 500 mT, TVEmf < 600 mT/s), but a small fraction were at medium/high levels; (4) Conclusion: Even under the “normal working conditions” defined for SEmf (STmf < 2T) by labour legislation (Directive 2013/35/EC), increased CMR usage increases vertigo-related hazards experienced by MRI personnel (a re-evaluation of electromagnetic safety hazards is suggested in the case of these or similar changes in work organisation).

Development of a Fast-Running Algorithm to Approximate Incident Blast Parameters Using Body-Mounted Sensor Measurements

ABSTRACT Introduction The Office of Naval Research sponsored the Blast Load Assessment-Sense and Test program to develop a rapid, in-field solution that could be used by team leaders, commanders, and medical personnel to make science-based stand-down decisions for service members exposed to blast overpressure. However, a critical challenge to this goal was the reliable interpretation of surface pressure data collected by body-worn blast sensors in both combat and combat training scenarios. Without an appropriate standardized metric, exposures from different blast events cannot be compared and accumulated in a service member’s unique blast exposure profile. In response to these challenges, we developed the Fast Automated Signal Transformation, or FAST, algorithm to automate the processing of large amounts of pressure–time data collected by blast sensors and provide a rapid, reliable approximation of the incident blast parameters without user intervention. This paper describes the performance of the FAST algorithms developed to approximate incident blast metrics from high-explosive sources using only data from body-mounted blast sensors. Methods and Materials Incident pressure was chosen as the standardized output metric because it provides a physiologically relevant estimate of the exposure to blast that can be compared across multiple events. In addition, incident pressure serves as an ideal metric because it is not directionally dependent or affected by the orientation of the operator. The FAST algorithms also preprocess data and automatically flag “not real” traces that might not be from blasts events (false positives). Elimination of any “not real” blast waveforms is essential to avoid skewing the results of subsequent analyses. To evaluate the performance of the FAST algorithms, the FAST results were compared to (1) experimentally measured pressures and (2) results from high-fidelity numerical simulations for three representative real-world events. Results The FAST results were in good agreement with both experimental data and high-fidelity simulations for the three case studies analyzed. The first case study evaluated the performance of FAST with respect to body shielding. The predicted incident pressure by FAST for a surrogate facing the charge, side on to charge, and facing away from the charge was examined. The second case study evaluated the performance of FAST with respect to an irregular charge compared to both pressure probes and results from high-fidelity simulations. The third case study demonstrated the utility of FAST for detonations inside structures where reflections from nearby surfaces can significantly alter the incident pressure. Overall, FAST predictions accounted for the reflections, providing a pressure estimate typically within 20% of the anticipated value. Conclusions This paper presents a standardized approach—the FAST algorithms—to analyze body-mounted blast sensor data. FAST algorithms account for the effects of shock interactions with the body to produce an estimate of incident blast conditions, allowing for direct comparison of individual exposure from different blast events. The continuing development of FAST algorithms will include heavy weapons, providing a singular capability to rapidly interpret body-worn sensor data, and provide standard output for analysis of an individual’s unique blast exposure profile.

Exposure Profile to Traffic Related Pollution in Pediatric Age: A Biomonitoring Study

The aim of this study was to trace an exposure profile to traffic-derived pollution during pediatric age. For this purpose, two biomonitoring campaigns for the determination of urinary (u-) methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE), tert-amyl methyl ether (TAME), and diisopropyl ether (DIPE) were carried out in two different periods of the year (summer 2017 and winter 2018), among a large sample of healthy children (n = 736; 5–11 years old) living in rural and urban areas in central Italy. The quantification of u-MTBE, u-ETBE, u-TAME, and u-DIPE was performed by HS-SPME-GC/MS technique and information on participants was collected by a questionnaire. u-DIPE concentrations resulted always under the LOQ. u-TAME mean levels were similar in both seasons (18.7 ng L−1 in summer vs. 18.9 ng L−1 in winter), while u-MTBE and u-ETBE levels were, respectively, 69.9 and 423.5 ng L−1 (summer) and 53.3 and 66.2 ng L−1 (winter). Main predictors of urinary excretion resulted the time spent in motor vehicles, being male and younger.

Psychopathology, Global Functioning, and ADHD Persistence in Relation to Childhood Adversity: A Latent Class Analysis Approach

We examine the impacts of childhood adversity on adult outcomes for women with and without childhood ADHD using an ethnically diverse sample of 140 participants with ADHD (Mage = 9.7) and 88 age- and ethnicity-matched comparison participants (Mage = 9.4). At adult follow-up, the sample included 211 of the original 228 participants (92.6% retention; Mage = 25.6). We used inclusive latent class analysis to identify profiles of childhood adversity; class membership was subsequently used in regression models to predict adult outcomes and ADHD persistence status. Key findings were as follows: (1) Four childhood adversity profiles emerged (Low Exposure, Familial Dysfunction, Maltreatment, Pervasive Exposure); (2) Compared with women with Low Exposure profile, those with Familial Dysfunction had significantly higher internalizing outcomes, whereas those in the Maltreatment and the Pervasive Exposure profiles were associated with lower global functioning and higher internalizing and externalizing behaviors; (3) Women with childhood ADHD in the Maltreatment profile were significantly more likely than those in the other profiles to show persistent ADHD in adulthood. Findings provide useful information about women who could be targeted for intervention; we discuss limitations and the need to investigate the confluence of neurodevelopmental conditions, like ADHD, and exposure to adverse child events.

Applications of Adductomics in Chemically Induced Adverse Outcomes and Major Emphasis on DNA Adductomics: A Pathbreaking Tool in Biomedical Research

Adductomics novel and emerging discipline in the toxicological research emphasizes on adducts formed by reactive chemical agents with biological molecules in living organisms. Development in analytical methods propelled the application and utility of adductomics in interdisciplinary sciences. This review endeavors to add a new dimension where comprehensive insights into diverse applications of adductomics in addressing some of society’s pressing challenges are provided. Also focuses on diverse applications of adductomics include: forecasting risk of chronic diseases triggered by reactive agents and predicting carcinogenesis induced by tobacco smoking; assessing chemical agents’ toxicity and supplementing genotoxicity studies; designing personalized medication and precision treatment in cancer chemotherapy; appraising environmental quality or extent of pollution using biological systems; crafting tools and techniques for diagnosis of diseases and detecting food contaminants; furnishing exposure profile of the individual to electrophiles; and assisting regulatory agencies in risk assessment of reactive chemical agents. Characterizing adducts that are present in extremely low concentrations is an exigent task and more over absence of dedicated database to identify adducts is further exacerbating the problem of adduct diagnosis. In addition, there is scope of improvement in sample preparation methods and data processing software and algorithms for accurate assessment of adducts.

Psychopathology, Global Functioning, and ADHD Persistence in Relation to Childhood Adversity: A Latent Class Analysis Approach

We examine the impacts of childhood adversity on adult outcomes for women with and without childhood ADHD using an ethnically diverse sample of 140 participants with ADHD (Mage = 9.7) and 88 age- and ethnicity-matched comparison participants (Mage = 9.4). At adult follow- up, the sample included 211 of the original 228 participants (92.6% retention; Mage = 25.6). We used inclusive latent class analysis to identify profiles of childhood adversity; class membership was subsequently used in regression models to predict adult outcomes and ADHD persistence status. Key findings were as follows: (1) Four childhood adversity profiles emerged (Low Exposure, Familial Dysfunction, Maltreatment, Pervasive Exposure); (2) Compared with women with Low Exposure profile, those with Familial Dysfunction had significantly higher internalizing outcomes, whereas those in the Maltreatment and the Pervasive Exposure profiles were associated with lower global functioning and higher internalizing and externalizing behaviors; (3) Women with childhood ADHD in the Maltreatment profile were significantly more likely than those in the other profiles to show persistent ADHD in adulthood. Findings provide useful information about women who could be targeted for intervention; we discuss limitations and the need to investigate the confluence of neurodevelopmental conditions, like ADHD, and exposure to adverse child events.

Reproductive Health Risks Associated with Occupational and Environmental Exposure to Pesticides

A marked reduction in fertility and an increase in adverse reproductive outcomes during the last few decades have been associated with occupational and environmental chemical exposures. Exposure to different types of pesticides may increase the risks of chronic diseases, such as diabetes, cancer, and neurodegenerative disease, but also of reduced fertility and birth defects. Both occupational and environmental exposures to pesticides are important, as many are endocrine disruptors, which means that even very low-dose exposure levels may have measurable biological effects. The aim of this review was to summarize the knowledge collected between 2000 and 2020, to highlight new findings, and to further interpret the mechanisms that may associate pesticides with infertility, abnormal sexual maturation, and pregnancy complications associated with occupational, environmental and transplacental exposures. A summary of current pesticide production and usage legislation is also included in order to elucidate the potential impact on exposure profile differences between countries, which may inform prevention measures. Recommendations for the medical surveillance of occupationally exposed populations, which should be facilitated by the biomonitoring of reduced fertility, is also discussed.

Exposure to metals and morbidity at eight years follow-up in women of childbearing age

This exploratory study was aimed to investigate the link between toxic metal content in women’s urine and their morbidity 2 years before and 6 years after the test. Concentrations of 25 metals in urine were analyzed for 111 pregnant women collected prior to delivery. All women were of Arab-Bedouin origin. Information on primary care and hospital visits during the study period was obtained. In a Poisson regression model, a health outcome was regressed over metal exposure and other factors. A Weighted Quantile Sum Regression (WQS) approach was used to indicate metals dominating in their possible impact on women's morbidity. Obesity was the most frequently diagnosed condition in this population (27.9%). Diagnoses in a neurological category accounted for 36.0%, asthma or respiratory—25.2%, psychiatric—12.6%, cardiovascular—14.4% and cancer or benign growth—for 13.5%. Based on WQS analysis, cancer and benign growth were mostly attributed to the increased levels of cadmium, cardiovascular outcomes were linked with lead, and obesity was found associated with elevated levels of nickel. Hematological, neurological and respiratory outcomes were attributed to multiple non-essential metals. The health and exposure profile of women in the study warrants a periodic biomonitoring in attempt to identify and reduce exposure to potentially dangerous elements.

Updated phase 1 results of teclistamab, a B-cell maturation antigen (BCMA) × CD3 bispecific antibody, in relapsed/refractory multiple myeloma (MM).

8007 Background: BCMA-targeted immunotherapies offer considerable promise for relapsed/refractory MM. Teclistamab (JNJ-64007957) is a BCMA × CD3 bispecific IgG4 antibody that redirects CD3+ T cells to BCMA-expressing MM cells. We present updated results of patients (pts) treated at the recommended phase 2 dose (RP2D) in the first-in-human phase 1 study of teclistamab. Methods: Eligible pts had MM and were relapsed, refractory or intolerant to established therapies. Primary objectives were to identify the RP2D (part 1) and characterize safety and tolerability of teclistamab at the RP2D (part 2). Teclistamab was given intravenously (IV; range 0.3–19.2 µg/kg [biweekly]; range 19.2–720 µg/kg [weekly]) or subcutaneously (SC; range 80.0–3000 µg/kg weekly) in different cohorts, with step-up dosing used for ≥38.4 µg/kg doses. Adverse events (AEs) were graded by CTCAE v4.03 (cytokine release syndrome [CRS] by Lee et al 2014). Response was assessed per IMWG criteria. Results: As of Feb 4, 2021, 156 pts received teclistamab (IV n = 84; SC n = 72). The RP2D, identified as weekly SC 1500 µg/kg teclistamab with 60.0 and 300 µg/kg step-up doses, was given to 40 pts (median follow-up 4.3 mo [range 1.1–10.4+]). Pts dosed at the RP2D (median age, 62.5 y [range, 39–84]; 65% male) had received a median of 5 prior lines of therapy (range 2–11; 100% triple-class exposed; 65% penta-drug exposed; 83% triple-class refractory; 35% penta-drug refractory; 85% refractory to their last line of therapy). There were no dose-limiting toxicities at the RP2D in part 1. The most common AEs at the RP2D were CRS (70%; grade 3/4 0) and neutropenia (60%; grade 3/4 40%); grade 1 neurotoxicity was reported in 1 (3%) pt. Median time to CRS onset was later with SC vs IV dosing (day after SC injection vs day of IV infusion). The overall response rate in response-evaluable pts treated at the RP2D (n = 40) was 65%; 58% achieved a very good partial response or better and 30% achieved a complete response (CR) or better; median time to first confirmed response was 1.0 mo (range 0.2–3.1). At the RP2D, median duration of response was not reached; 23 of 26 responders (88%), after median follow-up of 5.3 mo (range 1.2–10.4+), were alive and continuing on treatment with responses deepening over time. Of 14 evaluable pts across all cohorts, 9 with CR were minimal residual disease–negative at 10-6. At the RP2D, teclistamab exposure was sustained across the dosing interval and exceeded target levels, and consistent T cell activation was observed. Conclusions: Teclistamab at the RP2D (weekly 1500 µg/kg SC) was well-tolerated and showed encouraging efficacy with durable, deepening responses, supporting further investigation as monotherapy and in combination with other agents. With the extended exposure profile at the RP2D and delayed and low-grade CRS observed with SC administration, alternative SC dosing strategies are being explored. Clinical trial information: NCT03145181.