Revisiting the rationale of mandatory masking.

In this perspective, we review the evidence for the efficacy of face masks to reduce the transmission of respiratory viruses, specifically severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and consider the value of mandating universal mask wearing against the widespread negative impacts that have been associated with such measures. Before the SARS-CoV-2 pandemic, it was considered that there was little to no benefit in healthy people wearing masks as prophylaxis against becoming infected or as unwitting vectors of viral transmission. This accepted policy was hastily reversed early on in the pandemic, when districts and countries throughout the world imposed stringent masking mandates. Now, more than three years since the start of the pandemic, the amassed studies that have investigated the use of masks to reduce transmission of SARS-CoV-2 (or other pathogens) have led to conclusions that are largely inconsistent and contradictory. There is no statistically significant or unambiguous scientific evidence to justify mandatory masking for general, healthy populations with the intention of lessening the viral spread. Even if mask wearing could potentially reduce the transmission of SARS-CoV-2 in individual cases, this needs to be balanced against the physical, psychological and social harms associated with forced mask wearing, not to mention the negative impact of innumerable disposed masks entering our fragile environment. Given the lack of unequivocal scientific proof that masks have any effect on reducing transmission, together with the evident harms to people and the environment through the use of masks, it is our opinion that the mandatory use of face masks in the general population is unjustifiable and must be abandoned in future pandemic countermeasures policies.

Cross-validation of the peppermint benchmarking experiment across three analytical platforms.

The Peppermint Experiment is a breath analysis benchmarking initiative that seeks to address the lack of inter-comparability of outcomes across independent breath biomarker studies. In this experiment, the washout profiles of volatile terpene constituents of encapsulated peppermint oil (mainlyα-pinene,ß-pinene, limonene and 1,8-cineole) in exhaled breath are characterized through a series of measurements at defined sampling intervals up to 6 h after ingestion of the capsule. In the present work, the Peppermint Experiment was carried out on a cohort of volunteers (n= 11) that provided breath samples in three sittings on different days (i.e. triplicates per volunteer) for concurrent analysis by three different analytical platforms. These platforms were proton transfer reaction-time-of-flight-mass spectrometry (PTR-TOFMS) interfaced with a buffered end-tidal (BET) breath sampler, gas chromatography-ion mobility spectrometry (GC-IMS) in conjunction with a compatible handheld direct breath sampler, and thermal desorption comprehensive two-dimensional gas chromatography-time-of-flight-mass spectrometry (TD-GC×GC-TOFMS) with a Respiration Collection forin-vitroAnalysis (ReCIVA) system for trapping breath volatiles onto adsorbent tubes. Regression analysis yielded mean washout times across the cohort of 448 min (PTR-TOFMS and GC-IMS) and 372 min (TD-GC×GC-TOFMS), which are in good alignment with published benchmark values. Large variations in washout profiles were observed at the individuals level, both between (inter-individual) and within (intra-individual) participants, indicating high variability in the degree of absorption, distribution, metabolism and excretion of volatile terpenes in the body within individuals and across the cohort. The comparably low inter-instrument variability indicates that differences in benchmark values from independent studies reported in the literature are driven by biological variability rather than different performances between sampling methods or analytical platforms.

Emissions and uptake of volatiles by sampling components in breath analysis.

The first and most crucial step in breath research is adequate sampling, which plays a pivotal role in quality assurance of breath datasets. In particular, the emissions or uptake of volatile organic compounds (VOCs) by sampling interface materials present a risk of disrupting breath gas samples. This study investigated emissions and uptake by three interface components, namely a silicon facemask, a reusable 3D-printed mouthpiece adapter, and a pulmonary function test filter compatible with the commercial Respiration Collector forIn-VitroAnalysis (ReCIVA) breath sampling device. Emissions were examined before and after (hydro-)thermal treatment of the components, and uptake was assessed by exposing each material to 12 representative breath VOCs comprising alcohols, aldehydes, ketones, carboxylic acids, terpenes, sulphurous and nitrogenous compounds at different target concentration ranges (∼10 ppbVand ∼100 ppbV). Chemical analyses of VOCs were performed using proton transfer reaction-time-of-flight-mass spectrometry (PTR-TOFMS) with supporting analyses via thermal desorption comprehensive two-dimensional gas chromatography-TOFMS (TD-GC×GC-TOFMS). The filter exhibited the lowest overall emissions compared to the mask or adapter, which both had equivalently high emissions (albeit for different compounds). Treatment of the materials reduced the total VOC emissions by 62% in the mask, 89% in the filter and 99% in the adapter. Uptakes of compounds were lowest for the adapter and most pronounced in the mask. In particular, 1-butanol, acetone, 2-butanone, 1,8-cineole and dimethyl sulphide showed negligible uptake across all materials, whereas ethanol, nonanal, acetic acid, butanoic acid, limonene and indole exhibited marked losses. Knowledge of emissions and/or uptake by sampling components is key to reducing the likelihood of erroneous data interpretation, ultimately expediting progress in the field of breath test development.

Volatile Compound Emissions from Stereolithography Three-Dimensional Printed Cured Resin Models for Biomedical Applications.

Stereolithography three-dimensional printing is used increasingly in biomedical applications to create components for use in healthcare and therapy. The exposure of patients to volatile organic compounds (VOCs) emitted from cured resins represents an element of concern in such applications. Here, we investigate the biocompatibility in relation to inhalation exposure of volatile emissions of three different cured commercial resins for use in printing a mouthpiece adapter for sampling exhaled breath. VOC emission rates were estimated based on direct analysis using a microchamber/thermal extractor coupled to a proton transfer reaction-mass spectrometer. Complementary analyses using comprehensive gas chromatography-mass spectrometry aided compound identification. Major VOCs emitted from the cured resins were associated with polymerization agents, additives, and postprocessing procedures and included alcohols, aldehydes, ketones, hydrocarbons, esters, and terpenes. Total VOC emissions from cubes printed using the general-purpose resin were approximately an order of magnitude higher than those of the cubes printed using resins dedicated to biomedical applications at the respective test temperatures (40 and 25 °C). Daily inhalation exposures were estimated and compared with daily tolerable intake levels or standard thresholds of toxicological concerns. The two resins intended for biomedical applications were deemed suitable for fabricating an adapter mouthpiece for use in breath research. The general-purpose resin was unsuitable, with daily inhalation exposures for breath sampling applications at 40 °C estimated at 310 µg day-1 for propylene glycol (tolerable intake (TI) limit of 190 µg day-1) and 1254 µg day-1 for methyl acrylate (TI of 43 µg day-1).

Online Volatile Compound Emissions Analysis Using a Microchamber/Thermal Extractor Coupled to Proton Transfer Reaction-Mass Spectrometry.

Indoor air is a complex and dynamic mixture comprising manifold volatile organic compounds (VOCs) that may cause physiological and/or psychological discomfort, depending on the nature of exposure. This technical note presents a novel approach to analyze VOC emissions by coupling a microchamber/thermal extractor (µ-CTE) system to a proton transfer reaction-mass spectrometer (PTR-MS). This configuration provides an alternative to conventional emissions testing of small objects. The dynamic emission profiles of VOCs from a representative 3D-printed model are presented as a proof-of-concept analysis. Emission profiles are related to the target compound volatility, whereby 2-propanol and acetaldehyde exhibited the highest emissions and most rapid changes compared to the less volatile vinyl crotonate, 2-hydroxymethyl methacrylate, and mesitaldehyde, which were present at lower concentrations and showed different dynamics. Comparative measurements of the emission profiles of these compounds either with or without prior static equilibration yielded stark differences in their dynamics, albeit converging to similar values after 15 min of sampling time. Further, the utility of this system to determine the time required to capture a specific proportion of volatile emissions over the sampling period was demonstrated, with a mean duration of 8.4 ± 0.3 min to sample 50% of emissions across all compounds. This novel configuration provides a means to characterize the dynamic nature of VOC emissions from small objects and is especially suited to measuring highly volatile compounds, which can present a challenge for conventional sampling and analysis approaches. Further, it represents an opportunity for rapid, targeted emissions analyses of products to screen for potentially harmful volatiles.

Sampling Volatile Organic Compound Emissions from Consumer Products: A Review.

Volatile organic compounds (VOCs) are common constituents of many consumer products. Although many VOCs are generally considered harmless at low concentrations, some compound classes represent substances of concern in relation to human (inhalation) exposure and can elicit adverse health effects, especially when concentrations build up, such as in indoor settings. Determining VOC emissions from consumer products, such as toys, utensils or decorative articles, is of utmost importance to enable the assessment of inhalation exposure under real-world scenarios with respect to consumer safety. Due to the diverse sizes and shapes of such products, as well as their differing uses, a one-size-fits-all approach for measuring VOC emissions is not possible, thus, sampling procedures must be chosen carefully to best suit the sample under investigation. This review outlines the different sampling approaches for characterizing VOC emissions from consumer products, including headspace and emission test chamber methods. The advantages and disadvantages of each sampling technique are discussed in relation to their time and cost efficiency, as well as their suitability to realistically assess VOC inhalation exposures.

3D-printed mouthpiece adapter for sampling exhaled breath in medical applications.

The growing use of 3D printing in the biomedical sciences demonstrates its utility for a wide range of research and healthcare applications, including its potential implementation in the discipline of breath analysis to overcome current limitations and substantial costs of commercial breath sampling interfaces. This technical note reports on the design and construction of a 3D-printed mouthpiece adapter for sampling exhaled breath using the commercial respiration collector for in-vitro analysis (ReCIVA) device. The paper presents the design and digital workflow transition of the adapter and its fabrication from three commercial resins (Surgical Guide, Tough v5, and BioMed Clear) using a Formlabs Form 3B stereolithography (SLA) printer. The use of the mouthpiece adapter in conjunction with a pulmonary function filter is appraised in comparison to the conventional commercial silicon facemask sampling interface. Besides its lower cost - investment cost of the printing equipment notwithstanding - the 3D-printed adapter has several benefits, including ensuring breath sampling via the mouth, reducing the likelihood of direct contact of the patient with the breath sampling tubes, and being autoclaveable to enable the repeated use of a single adapter, thereby reducing waste and associated environmental burden compared to current one-way disposable facemasks. The novel adapter for breath sampling presented in this technical note represents an additional field of application for 3D printing that further demonstrates its widespread applicability in biomedicine.

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals.

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57.

Moving Chemistry from Bench to Market: An Introduction to the Agricultural and Food Chemistry Technical Program at the 260th American Chemical Society Fall 2020 Virtual Meeting & Expo.

This is the second special issue of the Journal of Agricultural and Food Chemistry (JAFC) that reviews the Agricultural and Food Chemistry Division (AGFD) technical program from a national meeting of the American Chemical Society (ACS). The 260th meeting was virtually held on August 17-20, 2020 as a result of the COVID-19 pandemic. Although it was the first-ever all online meeting in ACS history, a total of 311 abstracts were submitted to the AGFD technical program for oral and poster presentations and 34 technical sessions were held in 22 symposia, which covered a broad range of food and agricultural topics. The very first virtual ACS meeting was successful with the high quality of presentations, the number of online audiences, and seamless technology.

Breath Biomarkers in Diagnostic Applications.

The detection of chemical compounds in exhaled human breath presents an opportunity to determine physiological state, diagnose disease or assess environmental exposure. Recent advancements in metabolomics research have led to improved capabilities to explore human metabolic profiles in breath. Despite some notable challenges in sampling and analysis, exhaled breath represents a desirable medium for metabolomics applications, foremost due to its non-invasive, convenient and practically limitless availability. Several breath-based tests that target either endogenous or exogenous gas-phase compounds are currently established and are in practical and/or clinical use. This review outlines the concept of breath analysis in the context of these unique tests and their applications. The respective breath biomarkers targeted in each test are discussed in relation to their physiological production in the human body and the development and implementation of the associated tests. The paper concludes with a brief insight into prospective tests and an outlook of the future direction of breath research.

The peppermint breath test benchmark for PTR-MS and SIFT-MS.

A major challenge for breath research is the lack of standardization in sampling and analysis. To address this, a test that utilizes a standardized intervention and a defined study protocol has been proposed to explore disparities in breath research across different analytical platforms and to provide benchmark values for comparison. Specifically, thePeppermint Experimentinvolves the targeted analysis in exhaled breath of volatile constituents of peppermint oil after ingestion of the encapsulated oil. Data from thePeppermint Experimentperformed by proton transfer reaction mass spectrometry (PTR-MS) and selected ion flow tube mass spectrometry (SIFT-MS) are presented and discussed herein, including the product ions associated with the key peppermint volatiles, namely limonene,α- andß-pinene, 1,8-cineole, menthol, menthone and menthofuran. The breath washout profiles of these compounds from 65 individuals were collected, comprising datasets from five PTR-MS and two SIFT-MS instruments. The washout profiles of these volatiles were evaluated by comparing the log-fold change over time of the product ion intensities associated with each volatile. Benchmark values were calculated from the lower 95% confidence interval of the linear time-to-washout regression analysis for all datasets combined. Benchmark washout values from PTR-MS analysis were 353 min for the sum of monoterpenes and 1,8-cineole (identical product ions), 173 min for menthol, 330 min for menthofuran, and 218 min for menthone; from SIFT-MS analysis values were 228 min for the sum of monoterpenes, 281 min for the sum of monoterpenes and 1,8-cineole, and 370 min for menthone plus 1,8-cineole. Large inter- and intra-dataset variations were observed, whereby the latter suggests that biological variability plays a key role in how the compounds are absorbed, metabolized and excreted from the body via breath. This variability seems large compared to the influence of sampling and analytical procedures, but further investigations are recommended to clarify the effects of these factors.

Resource profile and user guide of the Polygenic Index Repository.

Polygenic indexes (PGIs) are DNA-based predictors. Their value for research in many scientific disciplines is growing rapidly. As a resource for researchers, we used a consistent methodology to construct PGIs for 47 phenotypes in 11 datasets. To maximize the PGIs' prediction accuracies, we constructed them using genome-wide association studies-some not previously published-from multiple data sources, including 23andMe and UK Biobank. We present a theoretical framework to help interpret analyses involving PGIs. A key insight is that a PGI can be understood as an unbiased but noisy measure of a latent variable we call the 'additive SNP factor'. Regressions in which the true regressor is this factor but the PGI is used as its proxy therefore suffer from errors-in-variables bias. We derive an estimator that corrects for the bias, illustrate the correction, and make a Python tool for implementing it publicly available.

Pursuing breath research in unprecedented circumstances-report from the Breath Biopsy Conference 2020.

The global outbreak of Sars-CoV-2 commencing early in 2020 had a dramatic impact on breath research, imposing abrupt restrictions but also presenting unforeseen opportunities. Taking place against the background of the COVID-19 pandemic, the 2020 Breath Biopsy Conference provided the breath research community with a platform to showcase and discuss the latest findings, including COVID-19 related research. As with most conferences under the present circumstance, it differed from its predecessor meetings by shifting to a virtual format, but retained its broad scope and interactive nature. The conference centred on four key themes, featuring applications of volatile organic compounds, breath biomarkers for liver disease, study design and data analytics, and, notably this year, breath-based endeavours to detect COVID-19 infection. This meeting report summarizes the events of the conference and spotlights selected contributions.

Exposure Assessment of Toxicologically Relevant Volatile Organic Compounds Emitted from Polymer-Based Costume Masks.

Plastic costume masks regularly exhibit unpleasant odors that may be associated with the emissions of volatile organic compounds (VOCs). Upon inhalation, VOCs might adversely affect the wearer's health if the exposure exceeds regulatory threshold values. The VOCs emitted from a selection of costume masks (n = 12) were characterized semiquantitatively with a screening method based on GC/MS measurements in dynamic headspace sampling mode. Furthermore, odors associated with the masks were evaluated by a sensory panel. Two masks emitted particularly high concentrations of ethylbenzene, xylenes, and cyclohexanone and exhibited the most intense and unpleasant odors, which were described as rubber-like, pungent, and leather-like. To simulate and assess the inhalation exposures for wearers of these masks, an innovative experimental setup based on a doll's head was developed, with sampling of emitted volatiles on adsorption material and subsequent analysis by thermal desorption-GC/MS. The measured inhalable concentrations of cyclohexanone exceeded the derived no-effect level (DNEL) for systemic effects on the general population over several hours of wearing, and also after repeated use. Importantly, the cyclohexanone DNEL was reevaluated in relation to a recent study on inhalation toxicity in rodents and was found to be significantly lower (1.4 mg·m-3) compared to the industry-derived values (10-20 mg·m-3), thus aggravating the health risks associated with inhalation exposure from some of the costume masks tested. Finally, a comparison of the inhalable concentrations derived from the simulated exposure assessments with those derived from measurements in miniaturized emission test chambers indicate that microchambers represent a useful tool for high-throughput analysis. The influences of temperature and inhalation/exhalation flow rates on VOC exposures were also studied.

Measuring and Controlling for the Compromise Effect When Estimating Risk Preference Parameters.

The compromise effect arises when being close to the "middle" of a choice set makes an option more appealing. The compromise effect poses conceptual and practical problems for economic research: by influencing choices, it can bias researchers' inferences about preference parameters. To study this bias, we conduct an experiment with 550 participants who made choices over lotteries from multiple price lists (MPLs). Following prior work, we manipulate the compromise effect to influence choices by varying the middle options of each MPL. We then estimate risk preferences using a discrete-choice model without a compromise effect embedded in the model. As anticipated, the resulting risk preference parameter estimates are not robust, changing as the compromise effect is manipulated. To disentangle risk preference parameters from the compromise effect and to measure the strength of the compromise effect, we augment our discrete-choice model with additional parameters that represent a rising penalty for expressing an indifference point further from the middle of the ordered MPL. Using this method, we estimate an economically significant magnitude for the compromise effect and generate robust estimates of risk preference parameters that are no longer sensitive to compromise-effect manipulations.

Factors affecting flavor perception in space: Does the spacecraft environment influence food intake by astronauts?

The intention to send a crewed mission to Mars involves a huge amount of planning to ensure a safe and successful mission. Providing adequate amounts of food for the crew is a major task, but 20 years of feeding astronauts on the International Space Station (ISS) have resulted in a good knowledge base. A crucial observation from the ISS is that astronauts typically consume only 80% of their daily calorie requirements when in space. This is despite daily exercise regimes that keep energy usage at very similar levels to those found on Earth. This calorie deficit seems to have little effect on astronauts who spend up to 12 months on the ISS, but given that a mission to Mars would take 30 to 36 months to complete, there is concern that a calorie deficit over this period may lead to adverse effects in crew members. The key question is why astronauts undereat when they have a supply of food designed to fully deliver their nutritional needs. This review focuses on evidence from astronauts that foods taste different in space, compared to on Earth. The underlying hypothesis is that conditions in space may change the perceived flavor of the food, and this flavor change may, in turn, lead to underconsumption by astronauts. The key areas investigated in this review for their potential impact on food intake are the effects of food shelf life, physiological changes, noise, air and water quality on the perception of food flavor, as well as the link between food flavor and food intake.

Breath research in times of a global pandemic and beyond: the game changer.

In contrast to blood and urine samples, breath is invisible and ubiquitous in the environment. Different precautions are now necessary beyond the usual 'Universal Precautions'. In the era of COVID-19, breath (especially the aerosol fraction) can no longer be considered as harmless in the clinic or laboratory. As Journal of Breath Research is a primary resource for breath-related research, we (the editors) are presently developing safety guidance applicable to all breath research , not just for those projects that involve known COVID-19 infected subjects. We are starting this process by implementing requirements on reporting safety precautions in research papers and notes. This editorial announces that authors of all new submissions to JBR henceforth must state clearly the procedures undertaken for assuring laboratory and clinical safety, much like the existing requirements for disclosing Ethics Committee or Institutional Review Board protocols for studies on human subjects. In the following, we additionally make some recommendations based on best practices drawn from our experience and input from the JBR Editorial Board.

Driving progress in exhaled breath biomarkers: Breath Biopsy Conference 2019.

November 2019 saw Cambridge, UK play host to the second Breath Biopsy Conference, a community-focused event aimed at sharing and supporting advancements in the collection and analysis of volatile organic compounds in exhaled breath. The event expanded upon the previous year's format, spanning two days and concluding with an expert panel discussion. Presentations covered detection, monitoring and precision medicine studies examining diseases including asthma, cirrhosis, cancer and tuberculosis. The meeting attracted representatives from diverse backgrounds, such as metabolomics, artificial intelligence, clinical research and chemical analysis. This meeting report offers an overview of what was presented and discussed during the conference.