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.

Microbial analyses of airborne dust collected from dormitory rooms predict the sex of occupants.

We have long known that human occupants are a major source of microbes in the built environment, thus raising the question: How much can we learn about the occupants of a building by analyzing the microbial communities found in indoor air? We investigated bacterial and fungal diversity found in airborne dust collected onto heating, ventilation, and air-conditioning (HVAC) air filters and settling plates from 91 rooms within a university dormitory. The sex of the room occupants had the most significant effect on the bacterial communities, while the room occupants had no significant effect on fungal communities. By examining the abundances of bacterial genera, we could predict the sex of room occupants with 79% accuracy, a finding that demonstrates the potential forensic applications of studying indoor air microbiology. We also identified which bacterial taxa were indicators of female and male rooms, and found that those taxa often identified as members of the vaginal microbiome were more common in female-occupied rooms while taxa associated with human skin or the male urogenital microbiota were more common in male-occupied rooms.

High temporal variability in airborne bacterial diversity and abundance inside single-family residences.

Our homes are microbial habitats, and although the amounts and types of bacteria in indoor air have been shown to vary substantially across residences, temporal variability within homes has rarely been characterized. Here, we sought to quantify the temporal variability in the amounts and types of airborne bacteria in homes, and what factors drive this variability. We collected filter samples of indoor and outdoor air in 15 homes over 1 year (approximately eight time points per home, two per season), and we used culture-independent DNA sequencing approaches to characterize bacterial community composition. Significant differences in indoor air community composition were observed both between homes and within each home over time. Indoor and outdoor air community compositions were not significantly correlated, suggesting that indoor and outdoor air communities are decoupled. Indoor air communities from the same home were often just as different at adjacent time points as they were across larger temporal distances, and temporal variation correlated with changes in environmental conditions, including temperature and relative humidity. Although all homes had highly variable indoor air communities, homes with the most temporally variable communities had more stable, lower average microbial loads than homes with less variable communities.

Role of mechanical ventilation in the airborne transmission of infectious agents in buildings.

Infectious disease outbreaks and epidemics such as those due to SARS, influenza, measles, tuberculosis, and Middle East respiratory syndrome coronavirus have raised concern about the airborne transmission of pathogens in indoor environments. Significant gaps in knowledge still exist regarding the role of mechanical ventilation in airborne pathogen transmission. This review, prepared by a multidisciplinary group of researchers, focuses on summarizing the strengths and limitations of epidemiologic studies that specifically addressed the association of at least one heating, ventilating and/or air-conditioning (HVAC) system-related parameter with airborne disease transmission in buildings. The purpose of this literature review was to assess the quality and quantity of available data and to identify research needs. This review suggests that there is a need for well-designed observational and intervention studies in buildings with better HVAC system characterization and measurements of both airborne exposures and disease outcomes. Studies should also be designed so that they may be used in future quantitative meta-analyses.

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.

Identification of SNPs located on BTA 6 and BTA 20 significantly associated with bovine respiratory disease in crossbred cattle.

The objective of the present study was to evaluate single nucleotide polymorphisms (SNPs) located in two quantitative trait locus (QTL) regions (BTA 6 and BTA 20) that are associated with bovine respiratory disease (BRD). A population of 323 crossbred steers sired by five purebred sire breeds during 2010-2013 (Angus, Braford, Braunvieh, Charolais, and Simmental) were evaluated for BRD susceptibility during the finishing process at a commercial feedlot. A total of 21 animals representing all sire breeds were affected with BRD at some time during the finishing process over the 4-year period. Although multiple sire breeds were evaluated in the present study, no sire breed effects were detected. A total of 82 SNPs were evaluated (58 on BTA 6 and 24 on BTA 20) in the present study for potential associations with BRD incidence. When evaluating the previously described QTL regions on BTA 6, three SNPs (rs42968895, rs42823614, and rs43448463) were significantly (P < 0.05) associated with BRD incidence. Another three SNPs (rs42477340, rs42512588, and rs42524468) were identified as significantly associated with BRD on the previously described BTA 6 QTL region. For both of these regions, animals inheriting different genotypes differed in BRD incidence during the finishing period. Although multiple SNPs were identified as being significantly associated with BRD incidence in the present study, these SNP associations should be validated in larger and more diverse populations.

Antioxidant therapies: a potential role in perinatal medicine.

Pregnancies complicated by impaired placentation, acute severe reductions in oxygen supply to the fetus, or intrauterine infection are associated with oxidative stress to the mother and developing baby. Such oxidative stress is characterized as an upregulation in the production of oxidative or nitrative free radicals and a concomitant decrease in the availability of antioxidant species, thereby creating a state of fetoplacental oxidative imbalance. Recently, there has been a good deal of interest in the potential for the use of antioxidant therapies in the perinatal period to protect the fetus, particularly the developing brain, against oxidative stress in complications of pregnancy and birth. This review will examine why the immature brain is particularly susceptible to oxidative imbalance and will provide discussion on antioxidant treatments currently receiving attention in the adult and perinatal literature - allopurinol, melatonin, α-lipoic acid, and vitamins C and E. In addition, we aim to address the interaction between oxidative stress and the fetal inflammatory response, an interaction that may be vital when proposing antioxidant or other neuroprotective strategies.

Glucocorticoid treatment does not alter early cardiac adaptations to growth restriction in preterm sheep fetuses.

OBJECTIVE: To study the consequences of glucocorticoid treatment in fetal growth restriction (FGR) on cardiac function. SETTING: Laboratory. SAMPLE: Sheep. METHODS: Growth restriction was induced in sheep fetuses using single umbilical artery ligation (SUAL) on days 105-110 of gestation (term 147). Control fetuses were not ligated. Betamethasone (BM) (11.4 mg intramuscularly) or saline was administered to ewes on days 5 and 6 after surgery. Ewes were anaesthetised on day 7, the fetuses were removed, and their hearts were mounted on a Langendorff apparatus. Balloon catheters were inserted into the right and left ventricles. OUTCOME MEASURES: Ventricular contractile function and infarct area following ischaemia/reperfusion. RESULTS: The SUAL resulted in FGR (body weight 77% of control). The FGR was associated with increases in basal left ventricular pressure development and rates of contraction and relaxation. Right ventricular contraction was unaffected. Following brief ischaemia/reperfusion, the infarct area in FGR hearts was increased four-fold compared with controls. Antenatal BM resulted in a proportional increase in heart size and coronary flow, especially in FGR fetuses, and left ventricular pressure and heart rate responses to ß-adrenoceptor activation were increased. CONCLUSIONS: Fetal hearts rapidly adapt to FGR to maintain substrate delivery to the brain and heart. The FGR greatly enhanced the area of ischaemia, with implications for susceptibility in postnatal life. Antenatal BM treatment does not interfere with these cardiac changes but appears to increase left ventricle ß-adrenoceptor responsiveness, which may render the offspring vulnerable to subsequent cardiac dysfunction.

Clathrate hydrates of air in antarctic ice.

Measurements of the dissociation pressure of nitrogen hydrate and oxygen hydrate show that the clathrate hydrate of air with the formula (N(2), O(2)) 6H(2)O should exist below about 800 meters in the Antarctic ice sheet. This accounts for the disappearance of gas bubbles at depths greater than 1200 meters. The hydrate should exist from this depth to prise 0.06 percent of the ice.

Phenylalanine and tyrosine synthesis under primitive earth conditions.

Phenylacetylene can be synthesized in substantial yields from various hydrocarbons by high temperatures, electric discharges, and ultraviolet light. Phenylacetylene is hydrated to phenylacetaldehyde by way of both nucleophilic and radical additions of H(2)S followed by hydrolysis of the thtioaldehyde. The addition of NH(3) and HCN to phenylacetaldehyde yields phenylalanine nitrile which is hydrolyzed to phenylalanine. A small yield of tyrosine is obtained from the radical addition of H(2)S to phenylacetylene. This sequence of reactions is a possible mechanism for the synthesis of these amino acids on the primitive earth.

Prebiotic synthesis of 5-substituted uracils: a bridge between the RNA world and the DNA-protein world.

Under prebiotic conditions, formaldehyde adds to uracil at the C-5 position to produce 5-hydroxymethyluracil with favorable rates and equilibria. Hydroxymethyluracil adds a variety of nucleophiles, such as ammonia, glycine, guanidine, hydrogen sulfide, hydrogen cyanide, imidazole, indole, and phenol, to give 5-substituted uracils with the side chains of most of the 20 amino acids in proteins. These reactions are sufficiently robust that, if uracil had been present on the primitive Earth, then these substituted uracils would also have been present. The ribozymes of the RNA world would have included many of the functional groups found in proteins today, and their catalytic activities may have been considerably greater than presently assumed.

Ammonium ion concentration in the primitive ocean.

If ion exchange on clay minerals regulated the cationts in the primitive ocean as it does in the present ocean, the pH would have been 8 and the K(+) concentration 0.01M. Since NH(4)(+) and K(+) are similar in their claymineral equilibria, the maximum NH(4) (+) concentration in the primitive ocean would also have been 0.01M. An estimate of the minimum NH(4)(+) concentratin is 1 x 10(-3)M, based on the reversible deamination of aspartic acid and the assumption that aspartic acid is necessary for the origin of life. The rate of this nonenzymic deamnination is rapid on the geological time scale.

Primitive earth synthesis of nicotinic acid derivatives.

Nicotinonitrile, 2-cyanopyridine, and 4-cyanopyridine can be synthesized under primitive earth conditions by the action of electric discharges on ethylene and ammonia. The electric discharge first synthesizes pyridine and hydrogen cyanide, which react in the discharge to form the cyanopyridines. Nicotinonitrile would have hydrolyzed in the primitive ocean to nicotinamide and nicotinic acid.

Carbon dioxide clathrate in the martian ice cap.

Measurements of the dissociation pressure of carbon dioxide hydrate show that this hydrate (CO(2) . 6H(2)O) is stable relative to solid CO(2) and water ice at temperatures above about 121 degrees K. Since this hydrate forms from finely divided ice and gaseous CO(2) in several hours at 150 degrees K, it is likely to be present in the martian ice cap. The ice cap can consist of water ice, water ice + CO(2) hydrate, or CO(2) hydrate + solid CO(2), but not water ice + solid CO(2).

Prebiotic synthesis of methionine.

Methionine has been shown to be a product of the action of a spark discharge on a simulated primitive earth atmosphere containing CH(4), N(2), NH(3), H(2)O, and H(2)S or CH(3)SH. Acrolein has also been shown to be a product of the discharge and is proposed as an intermediate in the prebiotic synthesis of methionine and of glutamic acid, homocysteine, homoserine, and alpha,gamma-diaminobutyric acid.

Inositol isomers: occurrence in marine sediments.

A combined gas chromatographic-mass spectrometric technique was used to identify and quantitate the occurrence of myo-, chiro-, and scyllo-inositol in marine sediments. The most abundant isomer was myo-inositol. These inositols were found in all the organic-rich sediment samples examined, and the amount of inositol decreased steadily with the age of the sample. A small fraction of the inositols occurred as hexaphosphate esters.

Temporal processing deficits of language-learning impaired children ameliorated by training.

Children with language-based learning impairments (LLIs) have major deficits in their recognition of some rapidly successive phonetic elements and nonspeech sound stimuli. In the current study, LLI children were engaged in adaptive training exercises mounted as computer "games" designed to drive improvements in their "temporal processing" skills. With 8 to 16 hours of training during a 20-day period, LLI children improved markedly in their abilities to recognize brief and fast sequences of nonspeech and speech stimuli.

Language comprehension in language-learning impaired children improved with acoustically modified speech.

A speech processing algorithm was developed to create more salient versions of the rapidly changing elements in the acoustic waveform of speech that have been shown to be deficiently processed by language-learning impaired (LLI) children. LLI children received extensive daily training, over a 4-week period, with listening exercises in which all speech was translated into this synthetic form. They also received daily training with computer "games" designed to adaptively drive improvements in temporal processing thresholds. Significant improvements in speech discrimination and language comprehension abilities were demonstrated in two independent groups of LLI children.

The Denver Aerosol Sources and Health (DASH) Study: Overview and Early Findings.

Improved understanding of the sources of air pollution that are most harmful could aid in developing more effective measures for protecting human health. The Denver Aerosol Sources and Health (DASH) study was designed to identify the sources of ambient fine particulate matter (PM(2.5)) that are most responsible for the adverse health effects of short-term exposure to PM (2.5). Daily 24-hour PM(2.5) sampling began in July 2002 at a residential monitoring site in Denver, Colorado, using both Teflon and quartz filter samplers. Sampling is planned to continue through 2008. Chemical speciation is being carried out for mass, inorganic ionic compounds (sulfate, nitrate and ammonium), and carbonaceous components, including elemental carbon, organic carbon, temperature-resolved organic carbon fractions and a large array of organic compounds. In addition, water soluble metals were measured daily for 12 months in 2003. A receptor-based source apportionment approach utilizing positive matrix factorization (PMF) will be used to identify PM (2.5) source contributions for each 24-hour period. Based on a preliminary assessment using synthetic data, the proposed source apportionment should be able to identify many important sources on a daily basis, including secondary ammonium nitrate and ammonium sulfate, diesel vehicle exhaust, road dust, wood combustion and vegetative debris. Meat cooking, gasoline vehicle exhaust and natural gas combustion were more challenging for PMF to accurately identify due to high detection limits for certain organic molecular marker compounds. Measurements of these compounds are being improved and supplemented with additional organic molecular marker compounds. The health study will investigate associations between daily source contributions and an array of health endpoints, including daily mortality and hospitalizations and measures of asthma control in asthmatic children. Findings from the DASH study, in addition to being of interest to policymakers, by identifying harmful PM(2.5) sources may provide insights into mechanisms of PM effect.

Nek3 kinase regulates prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells.

Prolactin (PRL) stimulates the cytoskeletal re-organization and motility of breast cancer cells. During PRL receptor signaling, Vav2 becomes phosphorylated and activated, an event regulated by the serine/threonine kinase Nek3. Given the regulatory role of Vav2, the function of Nek3 in PRL-mediated motility and invasion was examined. Overexpression of Nek3 in Chinese hamster ovary transfectants potentiated cytoskeletal re-organization in response to PRL. In contrast, downregulation of Nek3 expression by small-interfering RNA (siRNA) attenuated PRL-mediated cytoskeletal reorganization, activation of GTPase Rac1, cell migration and invasion of T47D cells. In addition, PRL stimulation induced an interaction between Nek3 and paxillin and significantly increased paxillin serine phosphorylation, whereas Nek3 siRNA-transfected cells showed a marked reduction in paxillin phosphorylation. Analysis of breast tissue microarrays also demonstrated a significant up-regulation of Nek3 expression in malignant versus normal specimens. These data suggest that Nek3 contributes to PRL-mediated breast cancer motility through mechanisms involving Rac1 activation and paxillin phosphorylation.