Practical Indicators for Risk of Airborne Transmission in Shared Indoor Environments and Their Application to COVID-19 Outbreaks.

Some infectious diseases, including COVID-19, can undergo airborne transmission. This may happen at close proximity, but as time indoors increases, infections can occur in shared room air despite distancing. We propose two indicators of infection risk for this situation, that is, relative risk parameter (Hr) and risk parameter (H). They combine the key factors that control airborne disease transmission indoors: virus-containing aerosol generation rate, breathing flow rate, masking and its quality, ventilation and aerosol-removal rates, number of occupants, and duration of exposure. COVID-19 outbreaks show a clear trend that is consistent with airborne infection and enable recommendations to minimize transmission risk. Transmission in typical prepandemic indoor spaces is highly sensitive to mitigation efforts. Previous outbreaks of measles, influenza, and tuberculosis were also assessed. Measles outbreaks occur at much lower risk parameter values than COVID-19, while tuberculosis outbreaks are observed at higher risk parameter values. Because both diseases are accepted as airborne, the fact that COVID-19 is less contagious than measles does not rule out airborne transmission. It is important that future outbreak reports include information on masking, ventilation and aerosol-removal rates, number of occupants, and duration of exposure, to investigate airborne transmission.

Nanotechnology against human cytomegalovirus in vitro: polyanionic carbosilane dendrimers as antiviral agents.

BACKGROUND: Human cytomegalovirus (HCMV) is a worldwide infection, causing different troublesome in immunosupressed patients and very related to Human Immunodeficiency Virus 1 (HIV-1) infection, mainly in developing countries, with a co-infection rate of 80% in Africa. The high cost of present treatments and the lack of routinely tests in these countries urge the necessity to develop new molecules or strategies against HCMV. The new treatments should be low-cost and capable of avoiding the emerging problem of resistant virus. Nanoparticles play an important role in several viral infections. Our main focus is to study the potential activity of polyanionic carbosilane dendrimers (PDC), which are hyperbranched molecules with several sulfonate or sulfate groups in their periphery, against different viruses. RESULTS: We studied the activity of G1-S4, G2-S16 and G2-S24P PDCs in MRC-5 cell line against HCMV infection by several plaque reduction assays. Our results show that dendrimers present good biocompatibility at the concentrations tested (1-50 µM) for 6 days in cell culture. Interestingly, both G2-S16 and G2-S24P showed a remarked inhibition at 10 µM against HCMV infection. Results on attachment and virucidal assays indicated that the inhibition was not directed to the virus or the virus-cell attachment. However, results of time of addition, showed a longer lasting activity of these dendrimers in comparison to ganciclovir, and the combination of G2-S16 or G2-S24P with ganciclovir increases the HCMV inhibition around 90 %. CONCLUSIONS: Nanotechnology, in particular polyanionic carbosilane dendrimers, have proved their potential application against HCMV, being capable of inhibiting the infection by themselves or enhancing the activity of ganciclovir, the actual treatment. These compounds represent a low-cost approach to fight HCMV infections.

Promising PEGylated cationic dendrimers for delivery of miRNAs as a possible therapy against HIV-1 infection.

BACKGROUND: The appearance of resistance against new treatments and the fact that HIV-1 can infect various cell types and develop reservoirs and sanctuaries makes it necessary to develop new therapeutic approaches to overcome those failures. RESULTS: Studies of cytotoxicity, genotoxicity, complexes formation, stability, resistance, release and particle size distribution confirmed that G2-SN15-PEG, G3-SN31-PEG, G2-SN15-PEG-FITC and G3-SN31-PEG-FITC dendrimers can form complexes with miRNAs being biocompatible, stable and conferring protection to these nucleic acids. Confocal microscopy and flow cytometry showed effective delivery of these four dendrimers into the target cells, confirming their applicability as delivery systems. Dendriplexes formed with the dendrimers and miRNAs significantly inhibited HIV-1 infection in PBMCs. CONCLUSIONS: These dendrimers are efficient delivery systems for miRNAs and they specifically and significantly improved the anti-R5-HIV-1 activity of these RNA molecules.

Anthropogenic control over wintertime oxidation of atmospheric pollutants.

During winter in the mid-latitudes, photochemical oxidation is significantly slower than in summer and the main radical oxidants driving formation of secondary pollutants, such as fine particulate matter and ozone, remain uncertain, owing to a lack of observations in this season. Using airborne observations, we quantify the contribution of various oxidants on a regional basis during winter, enabling improved chemical descriptions of wintertime air pollution transformations. We show that 25-60% of NOx is converted to N2O5 via multiphase reactions between gas-phase nitrogen oxide reservoirs and aerosol particles, with ~93% reacting in the marine boundary layer to form >2.5 ppbv ClNO2. This results in >70% of the oxidizing capacity of polluted air during winter being controlled, not by typical photochemical reactions, but from these multiphase reactions and emissions of volatile organic compounds, such as HCHO, highlighting the control local anthropogenic emissions have on the oxidizing capacity of the polluted wintertime atmosphere.

Split phosphorus fertiliser applications as a strategy to reduce incidental phosphorus losses in surface runoff.

Organic soils have low sorption capacities for phosphorus (P), and may pose a risk of P loss to water if P applications to these soils coincide with runoff events. Little is known about the magnitude of exports of P in overland flow following application of P fertiliser onto these soils, or on the influence of the frequency on P losses and persistence. The number of P fertiliser applications was surveyed across 39 commercial farms to assess current practice and inform the design of a rainfall runoff experiment to evaluate the effect of frequency of P applications on losses and persistence across time. Superphosphate (16% P) was applied in single (equivalent to 30 and 55 kg P ha-1 applied at day 0) and split (equivalent to 15 and 27.5 kg P ha-1 applied in two doses at days 0 and 55) applications to an organic soil inclined at a slope of 6% in a rainfall simulator experiment. The surface runoff of dissolved reactive phosphorus (DRP) was measured in controlled 30-min rainfall simulations conducted intermittently over an 85-day period. The DRP losses in surface runoff after the first rainfall event were 44.6 and 97.8 mg L-1 for single applications of 30 and 55 kg ha-1, respectively, and 13.3 and 21.8 mg L-1 for the same rates split in two doses, indicating that single P applications had disproportionately bigger impacts on losses than split applications. This supports the idea that frequent, but smaller, P applications can minimise the impact of fertilisation on waters. Dissolved reactive P concentrations remained significantly higher than those from the control samples until the end the experiment for almost all the P treatments, highlighting the long-lasting effects of added P and the elevated risk of P losses on organic soils. For climates with frequent rainfall events, which are likely to coincide with fertiliser applications, smaller but more frequent P applications can reduce the risk of P transfer as opposed to one single application.

Increased CD127+ and decreased CD57+ T cell expression levels in HIV-infected patients on NRTI-sparing regimens.

BACKGROUND: NRTIs-sparing regimens exert favourable profiles on T-cell homeostasis associated parameters. Our aim was to analyze the effect of NRTIs sparing regimen (NRTI-sparing-cART) vs NRTIs-containing regimen (NRTI-cART), on T-cell homeostasis associated parameters in naive HIV-infected patients. METHODS: Biomarkers of cell survival (CD127) and replicative senescence (CD57), were measured by multiparametric flow cytometry for T-cell phenotyping on peripheral blood mononuclear cells (PBMCs) samples just before (baseline) and after 48 weeks of undetectable viral load in patients on NRTI-sparing-cART (N = 13) and NRTI-cART (N = 14). After 48 weeks a subgroup of patients (n = 5) on NRTI-cART switched to NRTI-sparing-cART for another additional 48 weeks. In vitro assays were performed on PBMCs from HIV-uninfected healthy donors exposed or not to HIV. To analyze the independent factors associated with type of cART bivariate and stepwise multivariate analysis were performed after adjusting for basal CD4+, CD8+ and nadir CD4+ T-cell counts. RESULTS: After 48 weeks of a NRTI-sparing-cART vs NRTI-cART patients have higher effector memory (EM) CD4+ CD127+ T-cell levels, lower EM CD4+ CD57+ T-cell levels, higher CD8+ CD127+ T-cell levels, lower CD8+ CD57+ T-cell levels and higher memory CD8+ T-cell levels. This effect was confirmed in the subgroup of patients who switched to NRTI-sparing-cART. In vitro assays confirmed that the deleterious effect of a NRTIs-containing regimen was due to NRTIs. CONCLUSIONS: The implementation of NRTI-sparing regimens, with a favourable profile in CD127 and CD57 T-cell expression, could benefit cART-patients. These results could have potential implications in a decrease in the number of Non-AIDS events.

Microphysical explanation of the RH-dependent water affinity of biogenic organic aerosol and its importance for climate.

A large fraction of atmospheric organic aerosol (OA) originates from natural emissions that are oxidized in the atmosphere to form secondary organic aerosol (SOA). Isoprene (IP) and monoterpenes (MT) are the most important precursors of SOA originating from forests. The climate impacts from OA are currently estimated through parameterizations of water uptake that drastically simplify the complexity of OA. We combine laboratory experiments, thermodynamic modeling, field observations, and climate modeling to (1) explain the molecular mechanisms behind RH-dependent SOA water-uptake with solubility and phase separation; (2) show that laboratory data on IP- and MT-SOA hygroscopicity are representative of ambient data with corresponding OA source profiles; and (3) demonstrate the sensitivity of the modeled aerosol climate effect to assumed OA water affinity. We conclude that the commonly used single-parameter hygroscopicity framework can introduce significant error when quantifying the climate effects of organic aerosol. The results highlight the need for better constraints on the overall global OA mass loadings and its molecular composition, including currently underexplored anthropogenic and marine OA sources.

Contribution of human-related sources to indoor volatile organic compounds in a university classroom.

Although significant progress has been made in understanding the sources and chemistry of indoor volatile organic compounds (VOCs) during the past decades, much is unknown about the role of humans in indoor air chemistry. In the spring of 2014, we conducted continuous measurements of VOCs using a proton transfer reaction mass spectrometer (PTR-MS) in a university classroom. Positive matrix factorization (PMF) of the measured VOCs revealed a 'human influence' component, which likely represented VOCs produced from human breath and ozonolysis of human skin lipids. The concentration of the human influence component increased with the number of occupants and decreased with ventilation rate in a similar way to CO2 , with an average contribution of 40% to the measured daytime VOC concentration. In addition, the human skin lipid ozonolysis products were observed to correlate with CO2 and anticorrelate with O3 , suggesting that reactions on human surfaces may be important sources of indoor VOCs and sinks for indoor O3 . Our study suggests that humans can substantially affect VOC composition and oxidative capacity in indoor environments.

A deep learning model for Alzheimer's disease diagnosis based on patient clinical records.

BACKGROUND: Dementia, with Alzheimer's disease (AD) being the most common type of this neurodegenerative disease, is an under-diagnosed health problem in older people. The creation of classification models based on AD risk factors using Deep Learning is a promising tool to minimize the impact of under-diagnosis. OBJECTIVE: To develop a Deep Learning model that uses clinical data from patients with dementia to classify whether they have AD. METHODS: A Deep Learning model to identify AD in clinical records is proposed. In addition, several rebalancing methods have been used to preprocess the dataset and several studies have been carried out to tune up the model. RESULTS: Model has been tested against other well-established machine learning techniques, having better results than these in terms of AUC with alpha less than 0.05. CONCLUSIONS: The developed Neural Network Model has a good performance and can be an accurate assisting tool for AD diagnosis.

Laboratory studies on secondary organic aerosol formation from crude oil vapors.

Airborne measurements of aerosol composition and gas phase compounds over the Deepwater Horizon (DWH) oil spill in the Gulf of Mexico in June 2010 indicated the presence of high concentrations of secondary organic aerosol (SOA) formed from organic compounds of intermediate volatility. In this work, we investigated SOA formation from South Louisiana crude oil vapors reacting with OH in a Potential Aerosol Mass flow reactor. We use the dependence of evaporation time on the saturation concentration (C*) of the SOA precursors to separate the contribution of species of different C* to total SOA formation. This study shows consistent results with those at the DWH oil spill: (1) organic compounds of intermediate volatility with C* = 10(5)-10(6) µg m(-3) contribute the large majority of SOA mass formed, and have much larger SOA yields (0.37 for C* = 10(5) and 0.21 for C* = 10(6) µg m(-3)) than more volatile compounds with C*≥10(7) µg m(-3), (2) the mass spectral signature of SOA formed from oxidation of the less volatile compounds in the reactor shows good agreement with that of SOA formed at DWH oil spill. These results also support the use of flow reactors simulating atmospheric SOA formation and aging.

Pregnancy outcome in women exposed to leflunomide before or during pregnancy.

OBJECTIVE: Findings from animal studies have suggested that leflunomide may be a human teratogen. In the only human cohort study published to date, an increase in adverse outcomes in pregnancies after exposure to leflunomide was not detected. The aim of the present analysis was to expand on the previously published data with a description of birth outcomes among women who did not meet the previous cohort study criteria but who were exposed to leflunomide either during pregnancy or prior to conception. METHODS: Data on pregnancy exposures and outcomes were collected from 45 pregnant women who had contacted counseling services of the Organization of Teratology Information Specialists in the US or Canada between 1999 and 2009. Sixteen women were exposed to leflunomide during the first trimester of pregnancy and 29 women were exposed preconception. RESULTS: All 16 of the pregnancies with leflunomide exposure during pregnancy and 27 (93%) of the pregnancies with exposure prior to conception resulted in liveborn infants. There were 2 infants with major malformations from mothers who were exposed during pregnancy, and no malformations reported in the preconception group. There was a potential known alternative etiology for at least some of the defects observed. CONCLUSION: These data provide additional reassurance to women who inadvertently become pregnant while taking leflunomide and who undergo the washout procedure, as well as women who discontinue the medication prior to conception but have no prepregnancy documentation of drug clearance. However, until more conclusive data become available, women receiving leflunomide should be advised to use contraceptive methods and avoid pregnancy.

Response of an aerosol mass spectrometer to organonitrates and organosulfates and implications for atmospheric chemistry.

Organonitrates (ON) are important products of gas-phase oxidation of volatile organic compounds in the troposphere; some models predict, and laboratory studies show, the formation of large, multifunctional ON with vapor pressures low enough to partition to the particle phase. Organosulfates (OS) have also been recently detected in secondary organic aerosol. Despite their potential importance, ON and OS remain a nearly unexplored aspect of atmospheric chemistry because few studies have quantified particulate ON or OS in ambient air. We report the response of a high-resolution time-of-flight aerosol mass spectrometer (AMS) to aerosol ON and OS standards and mixtures. We quantify the potentially substantial underestimation of organic aerosol O/C, commonly used as a metric for aging, and N/C. Most of the ON-nitrogen appears as NO(x)+ ions in the AMS, which are typically dominated by inorganic nitrate. Minor organonitrogen ions are observed although their identity and intensity vary between standards. We evaluate the potential for using NO(x)+ fragment ratios, organonitrogen ions, HNO(3)+ ions, the ammonium balance of the nominally inorganic ions, and comparison to ion-chromatography instruments to constrain the concentrations of ON for ambient datasets, and apply these techniques to a field study in Riverside, CA. OS manifests as separate organic and sulfate components in the AMS with minimal organosulfur fragments and little difference in fragmentation from inorganic sulfate. The low thermal stability of ON and OS likely causes similar detection difficulties for other aerosol mass spectrometers using vaporization and/or ionization techniques with similar or larger energy, which has likely led to an underappreciation of these species.

Pyrocumulonimbus affect average stratospheric aerosol composition.

Pyrocumulonimbus (pyroCb) are wildfire-generated convective clouds that can inject smoke directly into the stratosphere. PyroCb have been tracked for years, yet their apparent rarity and episodic nature lead to highly uncertain climate impacts. In situ measurements of pyroCb smoke reveal its distinctive and exceptionally stable aerosol properties and define the long-term influence of pyroCb activity on the stratospheric aerosol budget. Analysis of 13 years of airborne observations shows that pyroCb are responsible for 10 to 25% of the black carbon and organic aerosols in the "present-day" lower stratosphere, with similar impacts in both the North and South Hemispheres. These results suggest that, should pyroCb increase in frequency and/or magnitude in future climates, they could generate dominant trends in stratospheric aerosol.

Impact of trash burning on air quality in Mexico City.

Air pollution experienced by expanding urban areas is responsible for serious health effects and death for millions of people every year. Trash burning is a common disposal method in poor areas, yet it is uncontrolled in many countries, and its contribution to air pollution is unclear due to uncertainties in its emissions. Here we develop a new trash burning emission inventory for Mexico City based on inverse socioeconomic levels and recently measured emission factors, and apply a chemistry-transport model to analyze the effects on pollutant concentrations. Trash burning is estimated to emit 25 tons of primary organic aerosols (POA) per day, which is comparable to fossil fuel POA emissions in Mexico City, and causes an increase in average organic aerosol concentrations of ∼0.3 µg m(-3) downtown and up to 2 µg m(-3) in highly populated suburbs near the sources of emission. An evaluation using submicrometer antimony suggests that our emission estimates are reasonable. Mitigation of trash burning could reduce the levels of organic aerosols by 2-40% and those of PM(2.5) by 1-15% over the metropolitan area. The trash burning contributions to carbon monoxide, nitrogen oxides, and volatile organic compounds were found to be very small (<3%), and consequently the contributions to secondary nitrate, sulfate, and secondary organic aerosols are also very small.

Acute toxicity of alkylpolyglucosides to Vibrio fischeri, Daphnia magna and microalgae: a comparative study.

In this paper, toxicity values of alkylpolyglucosides have been determined by applying the 24-h immobilization test with Daphnia magna, the LumiStox(®) 300 test which employs the luminescent bacteria Photobacterium phosphoreum and the test with Selenastrum capricornutum. Three alkylpolyglucosides with different alkyl chain and degree of polymerisation have been tested. For all tests, the results indicated that Vibrio fischeri was more sensitive to toxic effects from alkylpolyglucosides than was D. magna or S. capricornutum. The results demonstrate considerable variation in toxicity responses within structurally related glucose-based surfactants regardless of the species tested. The toxicity increased as the critical micelle concentration decreased, and as the alkyl chain length and resultant hydrophobicity increased.

Real-time methods for estimating organic component mass concentrations from aerosol mass spectrometer data.

We use results from positive matrix factorization (PMF) analysis of 15 urban aerosol mass spectrometer (AMS) data sets to derive simple methods for estimating major organic aerosol (OA) component concentrations in real time. PMF analysis extracts mass spectral (MS) profiles and mass concentrations for key OA components such as hydrocarbon-like OA (HOA), oxygenated OA (OOA), low-volatility OOA (LV-OOA), semivolatile OOA (SV-OOA), and biomass burning OA (BBOA). The variability in the component MS across all sites is characterized and used to derive standard profiles for real-time estimation of component concentrations. Two methods for obtaining first-order estimates of the HOA and OOA mass concentrations are evaluated. The first approach is the tracer m/z method, in which the HOA and OOA concentrations are estimated from m/z 57 and m/z 44 as follows: HOA ∼ 13.4 × (C(57) - 0.1 × C(44)) and OOA ∼ 6.6 × C(44), where C(i) is the equivalent mass concentration of tracer ion m/z i. The second approach uses a chemical mass balance (CMB) method in which standard HOA and OOA profiles are used as a priori information for calculating their mass concentrations. The HOA and OOA mass concentrations obtained from the first-order estimates are evaluated by comparing with the corresponding PMF results for each site. Both methods reproduce the HOA and OOA concentrations to within ∼30% of the results from detailed PMF analysis at most sites, with the CMB method being slightly better. For hybrid CMB methods, we find that fixing the LV-OOA spectrum and not constraining the other spectra produces the best results.

Effectiveness of a colonoscopic screening programme in first-degree relatives of patients with colorectal cancer.

AIM: The study aimed to assess the diagnostic yield of a colonoscopy screening programme in first-degree relatives of colorectal cancer (CRC) patients and to identify factors associated with advanced neoplasia. METHOD: We conducted a cross-sectional study. Individual characteristics, family trees and colonoscopy findings of asymptomatic first-degree relatives of CRC patients were collected. The findings were classified into cancer (invasive carcinoma and/or non-invasive high-grade neoplasia), high-risk adenomas (≥ 10 mm and/or a villous component) and low-risk adenomas (tubular < 10 mm). The dependent variable was the presence of advanced neoplasia, defined as cancer and/or high-risk adenoma. RESULTS: Two hundred and sixty-three relatives (147 females), 50.0 ± 11.5 (range, 25-75) years of age, agreed to participate out of a total of 618 who were invited (acceptance rate 42.5%). Index cases were diagnosed at 63.8 ± 12.4 (range, 37-88) years of age. The closest familial relationship was parent/offspring in 168 (63.9%) participants and sibling in 95 (36.1%) participants; 14.8% had three or more relatives with CRC/cancer associated with Lynch syndrome, and two or more affected generations were identified in 24.0%. Advanced neoplasia was found in 56 (21.3%) participants. Of these, invasive cancer, non-invasive high-grade neoplasia and high-risk adenomas were detected in five (1.9%), six (2.3%) and 45 (17.1%) participants, respectively. Low-risk adenomas were detected in 20 (7.6%) participants. Male sex (odds ratio, 2.59; P = 0.003) and sibling relationship (odds ratio, 2.74; P = 0.001) were independently associated with advanced neoplasia. CONCLUSION: We detected advanced neoplasia in a considerable number of participants. Our data support colonoscopy screening in first-degree relatives of patients with CRC at an earlier age than in the medium-risk population. Male sex and sibling relationship were predictors of advanced neoplasia.

Effect of concentration on the primary and ultimate biodegradation of alkylpolyglucosides in aerobic biodegradation tests.

This study examines the primary and ultimate biodegradation of a non-ionic surfactant, an alkylpolyglucoside, in ready biodegradability tests. The surfactant concentration was tested by the anthrone method, while the ultimate biodegradation (mineralization) was analyzed by the total organic carbon determinations. The influence of the concentration on the extent of primary and ultimate biodegradation and the kinetics of degradation also were determined. The primary and ultimate biodegradation was studied at different initial concentrations-15, 25, 50, 75, and 100 mg/L. The increasing concentration of test chemical from 15 to 100 mg/L resulted in a decrease in the relative maximum mineralization rate and longer estimated lag times by a factor of approximately 4.3. During the degradative process, two different stages were noted; these are better described with Quiroga and first-order kinetic models, respectively. For the study of the influence of concentration, the parameters characteristic of the biodegradation profiles in the different biodegradation assays were evaluated.

How did we get here: what are droplets and aerosols and how far do they go? A historical perspective on the transmission of respiratory infectious diseases.

The COVID-19 pandemic has exposed major gaps in our understanding of the transmission of viruses through the air. These gaps slowed recognition of airborne transmission of the disease, contributed to muddled public health policies and impeded clear messaging on how best to slow transmission of COVID-19. In particular, current recommendations have been based on four tenets: (i) respiratory disease transmission routes can be viewed mostly in a binary manner of 'droplets' versus 'aerosols'; (ii) this dichotomy depends on droplet size alone; (iii) the cut-off size between these routes of transmission is 5 µm; and (iv) there is a dichotomy in the distance at which transmission by each route is relevant. Yet, a relationship between these assertions is not supported by current scientific knowledge. Here, we revisit the historical foundation of these notions, and how they became entangled from the 1800s to today, with a complex interplay among various fields of science and medicine. This journey into the past highlights potential solutions for better collaboration and integration of scientific results into practice for building a more resilient society with more sound, far-sighted and effective public health policies.

Dismantling myths on the airborne transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

The coronavirus disease 2019 (COVID-19) pandemic has caused untold disruption throughout the world. Understanding the mechanisms for transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is key to preventing further spread, but there is confusion over the meaning of 'airborne' whenever transmission is discussed. Scientific ambivalence originates from evidence published many years ago which has generated mythological beliefs that obscure current thinking. This article collates and explores some of the most commonly held dogmas on airborne transmission in order to stimulate revision of the science in the light of current evidence. Six 'myths' are presented, explained and ultimately refuted on the basis of recently published papers and expert opinion from previous work related to similar viruses. There is little doubt that SARS-CoV-2 is transmitted via a range of airborne particle sizes subject to all the usual ventilation parameters and human behaviour. Experts from specialties encompassing aerosol studies, ventilation, engineering, physics, virology and clinical medicine have joined together to produce this review to consolidate the evidence for airborne transmission mechanisms, and offer justification for modern strategies for prevention and control of COVID-19 in health care and the community.