Nicolaides319 reported that fatty acids comprise about 25% of skin surface lipids

Mean outdoor values for palmitic and stearic acids were each in the approximate range 40-80 ng/m3. The mean I/O ratio for palmitic acid was 2.1 during cooler weather and 5.8 for warmer periods. The mean I/O ratio for stearic acid was 1.8 during cooler weather and 24 for warmer periods. Hasheminassab et al. subsequently reported on fine PM organic chemical composition for three of these study sites. They determined that “organic acids inside the retirement communities were dominated by indoor sources .” Total fine particle organic acid concentrations were in the approximate range 0.2-1.7 µg/m3 . Speciated concentrations were not reported. Human skin lipids contain a noteworthy abundance of n-alkanoic carboxylic acids, spanning a broad range of carbon numbers. Among the most prominent of these compounds are palmitic acid , myristic acid and stearic acid . Weitkamp et al. analyzed the fatty acids extracted from the hair of barber shop sweepings and detected the presence of nalkanoic carboxylic acids with carbon numbers ranging from 7 to 22 ; palmitic and stearic acids were especially abundant. Through the routine shedding of particles from the human envelope, one can anticipate that occupants are primary sources of these carboxylic acids in occupied spaces. The presence in indoor dust of squalene, a major skin lipid, reinforces the idea that occupants constitute emission sources of skin lipids to indoor environments. Daher et al. reported on the chemical characterization of both fine and coarse particles “inside the refectory of Santa Maria Delle Grazie Church, home of Leonardo Da Vinci’s ‘Last Supper.’” This highly controlled environment was well protected from the influence of outdoor air pollution. The investigators found, however, that “fatty acids … had high indoor-to-outdoor concentration ratios … showing a good correlation with indoor [fine-particle organic carbon mass concentrations],weed trimming tray implying a common indoor source.” In their supporting information, the authors report monthly concentrations of indoor n-alkanoic carboxylic acids from C14 through C29.

Averaged across all months, the three most abundant species were myristic , palmitic and stearic acids, with respective mean concentrations of 31, 27, 9.6 ng/m3 , which sum to 80% of the total for all n-alkanoic acids . Daher et al. noted that “potential indoor sources include skin emissions from visitors….” Kristensen et al.15 reported on time resolved measurements of gaseous and submicron particle-phase semivolatile organic compounds from a weeks-long sampling campaign in a normally occupied single-family home in northern California. That study identified cooking as an important source of indoor SVOCs, especially in the particle phase. The authors reported that, “the most abundant compounds related to cooking events include straight-chained saturated and unsaturated fatty acids .”Given this perspective, it should not be surprising that Liu et al.69 found dicarboxylic acids to be prominent organic components accumulated in indoor window films. Specifically, dicarboxylic acids with carbon numbers in the range 6 to 14 were the second or third most abundant class for most samples, behind monocarboxylic acids and comparable to n-alkanes . Among the dicarboxylic acids, azelaic acid, a product of ozone reacting with oleic acid, was generally the most abundant. Surface densities were highly variable across samples, with the highest reported value for azelaic acid being 7.3 µg m-2 on the indoor surface of an urban laboratory site in Toronto. Liu et al. inferred from their data that, “the greater accumulation of dicarboxylic acids in indoor rather than outdoor window films suggests indoor sources such as cooking.” With the high propensity to be in the condensed phase, it is worthwhile to consider whether dicarboxylic acids could materially influence the pH of indoor aqueous surface films. Consider the example of a surface film density of azelaic acid being 7.3 µg m-2. Assume that this abundance represents the sum of undissociated azelaic acid plus the two conjugate bases. Consider the influence on pH of surface water of this abundance of azelaic acid in isolation.

We do not have data on the abundance of water in the surface films studied by Liu et al. For exploration, consider three possibilities, corresponding to surface water thicknesses of 1 nm, 3 nm, and 10 nm. Also, assume that the surface water behaves thermodynamically like bulk water. Finally, neglect any substrate effects on aqueous film chemistry. This set of assumptions along with the reported pKa values in Table 17 allow for calculation of the equilibrium pH in the surface water. The results, in relation to the water film thickness, are pH = 3.0 for 1 nm, pH = 3.2 for 3 nm, and pH = 3.5 for 10 nm. Evidently, with such a highly favored aqueous phase, even the relatively weak azelaic acid can be sufficiently abundant to strongly acidify thin water films on indoor surfaces.In their classroom monitoring study, Liu et al.13 reported measurement results for 14 “diacid/hydroxycarbonyl acid ” compounds in the gas phase. Oxalic and malonic acid were reported as non-detectable indoors, even though there were substantial concentrations in outdoor air . The three most abundant diacids in indoor air reported in this study were succinic acid , glutaric acid , and adipic acid . The study by Liu et al.13 represents the most extensive and detailed set of gas-phase indoor organic acid data reported to date. Their supplemental information reports time average indoor and/or outdoor concentrations for 155 species. Table 18 reproduces the indoor and outdoor concentrations for the 18 species for which the time-averaged indoor concentration exceeded 10 ppt. Half of these species were reported as “not detected” in outdoor air. Among the remaining nine, the ratio of average indoor to average outdoor concentrations ranged from 4 to 25 , with a median ratio of 8. The consistently high I/O ratios reflects the importance of indoor emission sources for this group of abundant species. Wisthaler and Weschler326 have shown that these oxoacids are major secondary products of ozone/squalene chemistry, noting that squalene is a primary component of human skin lipids.In an extensive monitoring campaign undertaken in an ordinarily occupied single-family residence, Liu et al. reported on the gas-phase concentrations of a few other organic acids in addition to several n-alkanoic carboxylic acids. With tentative species identification, they reported that the time-average indoor concentration of acrylic acid was ppt during summer monitoring and 312 ppt during winter.

Analogously, glycolic acid was reported at 32 ppt for summer and 36 ppt for winter. Methanesulfonic acid was found to be present at an average abundance of 35 ppt in the summer and 115 ppt in the winter. In each case, the I/O ratio was well above 1.0, implicating indoor sources as important contributors to indoor concentrations. That study also reported an observation regarding a dicarboxylic acid: “Spikes of C2H3O4 + were observed during some occasions of sautéing in the summer.”The estimated average oxalic acid concentration in the summer season in the single-family residence was 16 ppt; in the winter, the average level was not stated, indicating that it was below the 10 ppt reporting threshold.In a follow-up investigation in Portugal, Alves et al. sampled PM10 inside and outside of a primary school classroom in the Aveiro city center during the winter and spring of 2011. They conducted detailed chemical analyses of composited samples, including measurements of diacids, cannabis grow setup ketoacids and aromatic acids. Table 20 records the reported indoor and outdoor concentrations for eight acidic species whose individual concentrations exceeded 10 ng/m3 . A striking feature is the extraordinarily high indoor concentration of malic acid. Alves et al. remarked that, “the fact that this acid is found in many sour or tart-tasting foods can eventually justify its detection at such high levels in indoor particles. The most common use of malic acid is in candy and potato chips.”Dehydroabietic acid and abietic acid are also known as “resin acids,” as they occur in tree resins. Resin acids occur in certain soaps. They are prominently emitted organic compounds from biomass burning. Noonan and coworkers have reported on indoor concentrations of abietic acid and dehydroabietic acid in PM2.5 samples collected in homes that used wood stoves for heat. The studies were conducted in association with a remediation program to improve the impact of wood stove use on ambient PM2.5 levels. Sampling in 16 homes, Ward and Noonan  reported average ± standard deviation indoor concentrations before the remediation to be 80 ± 61 ng/m3 for dehydroabietic acid and 3.7 ± 5.7 ng/m3 for abietic acid. Corresponding results for 21 homes as reported by Noonan et al. were 102 ± 73 ng/m3 for dehydroabietic acid and 8.8 ± 20 ng/m3 for abietic acid. The higher concentrations after remediation were attributed by the study authors to the more effective heating of fuel prior to its combustion in the higher efficiency stoves, leading to enhanced release into indoor air of these semivolatile wood constituents. Many studies have reported outdoor concentrations in the gas and/or particle phase for dicarboxylic and other organic acids reflecting urban and regional air quality concerns.

In summarizing selected results here, we focus on sampling conducted in urban and suburban environments, rather than in the more remote portions of the atmosphere, because of the implicit connection of urban studies to larger numbers of indoor environments and therefore greater relative significance for indoor air quality concerns, including human exposure. An early report by Kawamura and Kaplan characterized outdoor dicarboxylic acids in gas plus particle phases in the Los Angeles area from sampling during summer and autumn of 1984. They concluded that “oxalic acid is the dominant species.” Considering the sum of C2-C6 plus C9 , the total average concentration ± standard deviation for 12 atmospheric samples was 8.3 ± 4.5 nmol/m3 . The three most prominent species were oxalic acid , succinic acid and adipic acid . An early study in Tokyo sampled at intervals between late spring and autumn 1989. In that study, dicarboxylic and ketocarboxylic acids were assessed for the particle-phase only, with no particle size cutoff. The total average mass concentration of n-alkanoic dicarboxylic acids spanning C2 to C10 was 440 ng/m3 with the three most prominent species being oxalic acid , malonic acid and succinic acid .Among the total of 24 reported acids, only two other species had reported average concentrations above 30 ng/m3 : pyruvic acid and glyoxylic acid . Altogether, diacid concentrations averaged 540 ng/m3 and ketoacids 98 ng/m3 .Rogge et al. conducted detailed organic chemical composition analysis for fine particles collected outdoors at uniform intervals for year 1982 at four sites in the Los Angeles area. The average concentration of total aliphatic dicarboxylic acids was 239 ng/m3 . The four most abundant species were succinic acid , malonic acid , azelaic acid , and glutaric acid . These four species contributed 70% of the total mass concentration reported for aliphatic dicarboxylic acids. Oxalic acid was not reported. Khwaja collected and analyzed seven atmospheric samples collected over two days during October 1991 in a semiurban area of New York state. They reported concentrations of oxocarboxylic, ketocarboxylic, and dicarboxylic acids in the particle phase. Average ± standard deviation levels were 231 ± 118 ng/m3 for oxalic acid, 119 ± 44 ng/m3 for succinic acid, 84 ± 20 ng/m3 for malonic acid, 59 ± 21 ng/m3 for pyruvic acid, and 44 ± 16 ng/m3 for glyoxalic acid. Several recent studies have reported particle-associated organic acids sampled from outdoor air in and near Beijing, China. 336-339 Results from one illustrative study are highlighted in Table 21, which reports a subset of species for which the annual average ambient concentration of the analyte in PM2.5 was above 10 ng/m3 . Several dicarboxylic acids are featured, with oxalic acid being the most abundant. Seasonally, the average ± standard deviation for total dicarboxylic acid concentrations varied from a low of 366 ± 261 ng/m3 in autumn to a high of 763 ± 701 ng/m3 in winter. Among the other prominent organic acids quantified in PM2.5 in Beijing are phthalic acid and terephthalic acid, whose structures and thermodynamic properties are illustrated in Figure 16 and its caption.Cooking is a major air pollutant emission source. Even though most cooking occurs indoors, because of the much greater overall research emphasis on outdoor air pollution, most studies on emissions of organic acids from cooking activities have focused on larger-scale cooking operations, e.g. as practiced in restaurants or in the food-preparation industry, rather than from residential cooking. Abdullahi et al. have reviewed emissions from cooking of particulate matter and associated chemical components.

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The concentrations of NO2 and NO were not affected by humans in the chamber

The lower average values for HONO in AC homes may partially reflect HONO loss to the air conditioner condensate. Dividing these same 58 homes between those with gas stoves and those without, average HONO concentrations were 0.8 ± 0.8 ppb in non-gas-stove homes and 4.0 ± 2.8 ppb in gasstove homes . During winter months, Leaderer et al. measured average HONO concentrations to be 6.8 ± 6.1 ppb in kerosene-heater homes and 3.5 ± 3.6 ppb in nonkerosene heater homes .For the homes without kerosene heaters, average wintertime HONO concentrations were 2.4 ± 3.1 ppb in non-gas-stove homes and 5.5 ± 3.8 ppb in gas-stove homes . All of this evidence points to unvented combustion as contributing to measurable increases in indoor HONO levels.In 99 homes in Upland, CA, and San Bernardino County, Lee et al.measured average HONO concentrations of 4.6 ± 4.3 ppb, considerably higher than the outdoor levels of 0.9 ± 2.3 ppb. Homes with gas ranges had higher indoor NO2 and HONO concentrations than those without. Indoor concentrations of HONO were positively correlated with NO2, with HONO levels occurring at approximately 17% of the NO2 levels. HONO concentrations were inversely correlated with O3 concentrations. A similar inverse correlation between HONO and O3 was reported by Weschler et al.based on spot measurements made in a Burbank telecommunications office. In both studies, the authors suggest that this observation may be a result of ozone-initiated oxidation of nitrite ions in aqueous surface films; the concentration of nitrite ions in indoor aqueous solutions is linked to gas-phase HONO concentrations . Semi-continuous measurements of HONO concentrations were made in an unoccupied school classroom in France,planting racks using wet chemical sampling and subsequent quantification with high performance liquid chromatography. Five experiments were conducted with controlled injections of NO2 under different lighting and relative humidity conditions.

With average indoor NO2 levels in the range 28-46 ppb and indoor RH levels in the range 30-60%, average indoor HONO levels were 5.1-6.2 ppb. Mendez et al. developed a description for HONO formation that assumes NO2 is first sorbed to surface sites, which are limited in number, and that NO2 then reacts with water to produce HONO and HNO3. Key parameters were fitted based on measurements in one experiment, and, with these fitted parameters, the model reasonably predicted the measured HONO concentrations in the other four experiments. As part of a study in a Syracuse home, Zhou et al. made time-resolved measurements of HONO concentrations during baseline conditions and cooking events. Mean ± standard deviation HONO concentrations were 4.3 ± 2.2 ppb during baseline conditions, rising to 19.5 ± 10.5 ppb during cooking . A short-term peak concentration of 50 ppb was measured. To our knowledge, this is the first study to report indoor baseline HONO concentrations larger than indoor baseline NO2 concentrations . Collins et al. measured time-resolved HONO levels inside and outside a Toronto home in November using a high-resolution time-of-flight chemical ionization mass spectrometer with acetate as the reagent ion. They found that, while indoor NO2 levels varied over a large range depending on outdoor levels, indoor HONO concentrations varied over a relatively narrow range and did not correlate with NO2 concentrations. Perturbation experiments were conducted in the kitchen using a burner on a gas stove and opening/closing windows and a door. During these perturbations, NO2 emitted by the gas burner only weakly affected HONO levels. Flushing the kitchen via open windows and a door reduced HONO levels during the high ventilation period, but when windows and door were closed, HONO returned to a gas-phase concentration close to its pre-airing value. The temporal responses of HONO were similar to those of small carboxylic acids in these airing experiments.

The authors concluded that gas-phase HONO was in equilibrium with, and strongly controlled by, surface sources. This inference was further supported by nitrite levels measured on various impermeable vertical surfaces in the kitchen and the upstairs of the home. Nitrite levels averaged approximately 1012 molecules cm-2 ; the authors cautioned that this value should be considered a lower limit. HONO measurements that were made during venting experiments as part of the HOMEChem campaign in Austin TX158 substantiate the Toronto home findings by Collins et al.When the Austin test house was vented, gas-phase HONO concentrations decreased from ~ 4 ppb to about 1 ppb. When windows were then closed, the HONO concentration returned to a level close to that measured before venting. See §4.6 for further discussion. It is interesting to compare the influence of HONO to that of HNO3 on the pH of aqueous surface films or bulk water. To begin, consider that the equilibrium pH of water exposed to 800 ppm of CO2 and 20 ppb of NH3 is 7.12. Adding 5 ppb of gaseous HONO to this mix would decrease the equilibrium pH to 6.53, whereas adding 0.1 ppb of HNO3 would decrease the equilibrium pH to 3.48. So, although measured indoor concentrations of HONO tend to be 10- 100´ larger than those of HNO3, the expected influence of HONO on pH is considerably weaker, based on analyses for equilibrium conditions. Taken together, these studies illustrate a strong direct contribution from indoor combustion to indoor HONO concentrations, a contribution from the partial transformation of NO2 to HONO on indoor surfaces, the potential for ozone to decrease indoor HONO levels via oxidation of nitrite ions in aqueous solution, and the ability of indoor basic surfaces to serve as large reservoirs for nitrous acid. More measurements of nitrite ions on indoor surfaces, as well as of the time-dependent pH of aqueous films on different indoor surfaces, would improve our understanding of the reported and inferred dynamics of this inorganic acid.During a study conducted in a 79-m3 stainless steel climate chamber, Brauer et al. examined the impact of human occupants on indoor HONO concentrations.

At a high air-exchange rate , four human occupants had only a small effect on HONO concentrations resulting from the addition of NO2 to the chamber. However, at a much lower air-exchange rate , the measured indoor HONO concentration with occupants was reduced to 40% of its value without humans in the chamber . When the subjects left the chamber, HONO levels returned to levels previously observed for the empty chamber.Direct removal by breathing could not account for the observed HONO removal rate. Reaction of HONO with NH3 emitted by the occupants also did not explain the observed reduction of indoor HONO levels. Brauer et al. speculated that “the effect of increased surface area is a plausible explanation for our observations.”One can estimate the potential magnitude of HONO removal by exposed skin, hair and clothing of the four subjects in the chamber. Assume that the deposition velocity for HONO to human surfaces is similar to that measured for ozone and assume a body surface area of 1.8 m2 for each human in the chamber. Then four humans would remove HONO at a rate equivalent to ventilating with clean air at 58 m3 /h or 0.73 h-1 in the 79 m3 chamber. Such a removal by human occupants is predicted to yield a reduction of approximately 60% in HONO concentration at a chamber air exchange rate of 0.5 h-1 , which is consistent in scale with the reduction shown in Figure 4 of Brauer et al.Conversely, the effect of removal on human surfaces would only be expected to reduce the indoor concentrations of HONO by about 5% for the high air-exchange rate condition of 12 h-1. If HONO loss does occur on the occupant envelope,sub irrigation cannabis important questions remain to be answered. Is this phenomenon transient, terminating when equilibrium partitioning is achieved? Or is HONO being irreversibly sorbed by skin and clothing? Based on 48-h measurements of O3 and NO2 in a Southern California museum gallery, coupled with their model of indoor chemistry, Nazaroff and Cass200 predicted that O3/NO2 chemistry would generate NO3 and N2O5 at substantial net rates. Weschler et al.suggested that under certain circumstances, O3/NO2 chemistry would generate indoor nitrate radical concentrations comparable to outdoor nighttime levels and that subsequent chemistry could be a substantial source of indoor nitric acid. Using a detailed chemical model, Sarwar et al. estimated an indoor nitrate radical concentration of 0.15 ppt for “base case” indoor conditions. Using a detailed model of gas-phase indoor chemistry, Carslaw predicted low NO3 concentrations under indoor conditions that included elevated concentrations of terpenes and unsaturated alkenes, which rapidly consume nitrate radicals. Carslaw noted that an anticipated consequence is formation of RO2·radicals, and subsequent production of organic acids. Nøjgaard made the first time-integrated measurements of the sum ‘NO3 + N2O5’ based on concentrations of an oxidation product of the NO3/cyclohexene reaction. Eleven separate measurements were made in an unoccupied 60 m3 conference room in Copenhagen, DK, during August. There were no indoor sources of O3 or NO2; these species originated outdoors.

The sum ‘NO3 + N2O5’ ranged from 1 to 58 ppt, and was influenced by the fraction of time mechanical ventilation occurred, levels of O3 and NO2, lighting and time of day. For the four samples collected during daylight hours, the sum of NO3 + N2O5 ranged from 3 to 10 ppt or approximately 0.6 to 1.4 ppt of NO3 given the measured cooccurring NO2 concentrations. These measured values are larger than Carslaw’s modeled estimates of NO3 levels under typical indoor conditions. Nøjgaard speculated that this discrepancy might be due to actual NO concentrations being lower than those used in the model and concluded by calling for time-resolved measurements of indoor NO3, such as could be achieved using cavity ring down spectroscopy. Arata et al. made the first real-time indoor NO3 measurements in the kitchen of a single family home during simulated-use conditions. Experiments included cooking with a butane stove in the presence of deliberately released ozone. At an enhanced O3 level of 40 ppb, researchers ignited the stove, operated it for about five minutes to boil water, and turned it off. After O3 had titrated the NO in the kitchen air, the N2O5 level began to increase, reaching a value of 190 ppt, while the NO3 concentrations leveled off at about 3 ppt. Based on simultaneous measurements of NO2, O3 and NO3, they estimated total nitrate radical reactivity with volatile organic compounds to be 0.8 s-1 . Using a box-model they calculated a peak NO3 production rate of 7 ppb h-1 . The model’s output indicated that reaction of N2O5 with indoor surfaces, producing nitric acid, accounted for 20% of NO3 loss during the period of peak NO3 production. More generally, these studies indicate that, under conditions with elevated indoor levels of O3, combustion events can result in meaningful levels of nitric acid, organonitrates and various oxidized VOC – even when measured residual NO3 concentrations are relatively low.Isocyanic acid is moderately acidic and moderately soluble . It has been recognized as a gas-phase acid in the outdoor atmosphere since 2008. More recently, experiments have demonstrated that gas-phase oxidation of nicotine by hydroxyl radicals generates HNCO. Measurements using an acetate CIMS in a chamber and in a Toronto home have explored indoor sources of HNCO. 238 The chamber studies indicated a molar ratio of HNCO/CO in side stream cigarette smoke of 2.7 × 10-3 . In a home, the background HNCO concentration was 0.15 ppb, about twice the outdoor level. A single cigarette’s side stream smoke increased the HNCO concentration to about 1.5 ppb. In chamber experiments, there was evidence for photochemical production of HNCO from cigarette smoke, doubling the concentration in about 30 minutes at an OH concentration of 1.1 × 107 molecules/cm3. However, in the home there was no evidence of photochemistry influencing the HNCO concentration. Simultaneous, time-resolved measurements of HNCO and CO indicated that partitioning to indoor surfaces was a significant sink for indoor HNCO. Isocycanic acid reacts with ammonia to form urea. Among halogenated acids, chlorine-containing species are the most noteworthy. In the atmosphere, hydrochloric acid is a prominent atmospheric inorganic strong acid. Important sources of atmospheric HCl are the combustion of fuels and wastes that contain chlorine, which include coal, bio-fuels, and plastics. Hydrochloric acid is also generated from acid-displacement reactions in which other atmospheric strong acids, such as HNO3, react with sea-salt aerosol, with the net effect represented by HNO3 + NaCl ® HCl + NaNO3. In a global emission inventory of HCl, combustion and sea-salt dechlorination were the largest sources.

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Dermal emission rates were found to be substantially larger than breath emission rates

Although most of the experiments measured whole-body emission rates, a subset of experiments measured dermal and breath emissions separately. Over the range of conditions studied, the measured NH3 emission rates ranged from 0.4 to 5.4 mg h-1 person-1 . These values are much lower than the per person NH3 emission rates reported almost 30 years earlier in Table 4 of Lee and Longhurst.Based on current literature, we judge that the NH3 emission rate of a typical adult is dominated by emissions from skin, is influenced by temperature, sweating, fraction of exposed skin, and is commonly in the range of 0.3 to 5 mg NH3 h-1 person-1 = 2 to 36 g NH3-N y-1 person-1. Humans also contribute to indoor NH3 levels via their skin squames . In mechanically ventilated buildings, squames can accumulate in HVAC systems. Ng et al.report the generation of NH3 and volatile fatty acids via bacteria acting on skin squames in air cooling units. Temperature was seen to have a pronounced effect on NH3 generation. Insufficient information was reported to quantitatively estimate an emission rate from this source under typical building conditions. Concrete treated with urea-based antifreeze during mixing can be a substantial source of ammonia. Bai et al. measured NH3 emissions to vary with air-exchange rate in the range 1-6 mg m-2 h-1 for samples prepared with about 1 kg of urea per 300 kg of concrete. The investigators estimated that, at typical ventilation rates, it would take more than ten years to exhaust the ammonia emanating from their concrete samples. They also made measurements in five undecorated apartments in a building that had been built four years earlier with concrete containing urea. The mean NH3 concentrations in the bedrooms and living rooms were approximately 5000 ppb when windows and outside doors were closed and were slightly above 1000 ppb when the apartments were ventilated.

Lindgren116 measured ammonia levels between 3000 and 6000 ppb in a newly built Beijing office,growers equipment reporting that additives in the concrete were the likely cause of the high values. Jang et al. examined how the organic content of the aggregate affected NH3 emissions from different cement mortars. The NH3 emitted from the aggregate increased with the mass fraction of organic matter in the aggregate. Due to the potential for NH3 emissions from concrete, Chinese buildings are often tested for ammonia. While it is well known that environmental tobacco smoke contains elevated levels of NH3, direct measurements of the influence of smoking on indoor NH3 levels are scarce. Risner and Conner100 report a mean ammonia concentration of 107 µg/m3 in a 28 m3 room in which four cigarettes had been smoked. No information was reported on occupancy or air-exchange rate. In addition to NH3 generated by the combustion of tobacco, NH3 in ETS can also be a consequence of the deliberate addition of ammonia-forming compounds to cigarettes. Ammonia increases the fraction of nicotine that is present in ETS as the free base in contrast to the protonated form. The free-base nicotine is more readily absorbed by the smoker. Pankow et al. have investigated the partitioning of nicotine between particles and the gas phase in ETS and mainstream smoke. See also §3.10.Indoor ammonia concentrations tend to be much larger than outdoor concentrations. Ampollini et al. have assembled an extensive summary of indoor ammonia measurements reported in the peer-reviewed literature. Table 6 summarizes indoor and outdoor ammonia concentrations measured in representative studies. Ammonia measurements indoors first appeared in the literature in the late 1980s and early 1990s. Sisovic et al. measured indoor NH3 levels multiple times in six offices spanning five buildings in Zagreb, Yugoslavia, during summer and winter. The mean summer concentration was 74 µg/m3 ; the mean winter concentration was 67 µg/m3 . This outcome suggests substantially higher indoor NH3 emission rates in summer, since air-exchange rates were presumably lower in winter.

Li and Harrison119 measured indoor and outdoor NH3 levels at University of Essex buildings. They found that indoor levels were 3.5 to 21 times the corresponding outdoor levels; indoor levels ranged from 7 to 48 µg/m3 with a mean value of 20 µg/m3 . Atkins and Lee120 made repeated measurements in 10 British homes. The mean NH3 concentrations in kitchens, living rooms and bedrooms were 39, 37, and 32 µg NH3-N/m3, respectively . During winter months, Tidy and Cape121 measured NH3 concentrations in houses and public buildings in Edinburgh. In private living rooms, NH3 levels ranged from 7 to 63 ppb with higher values where smoking occurred. A similar range of values was found in public buildings. More recently , researchers in Finland have measured NH3 concentrations in newly constructed apartments and residences , as well as office buildings with indoor air problems . In Prague, NH3 measurements were made at the historic National Library, which is naturally ventilated. During warmer months the monthly mean NH3 concentrations were somewhat larger than those measured during cooler months of December-March . Researchers from Kumamoto University, using a novel automated flow-based ammonia gas analyzer, measured a mean NH3 concentration of 28 ppb in their university laboratory. The values reported in Table 6 are for occupied environments. Investigators from Lawrence Berkeley National Laboratory measured NH3 concentrations in an unoccupied home in Clovis, CA. During the months of October, December and January, the mean levels were 21, 17 and 15 ppb, respectively. These indoor values were only slightly larger than co-occurring outdoor values. In more comprehensive multi-pollutant studies, Brauer et al., Liang and Waldman and Suh et al. measured indoor NH3 and examined its relationship to aerosol strong acidity. Brauer et al., sampling in Boston homes, found that NH3 concentrations were higher indoors than outdoors, with mean indoor NH3 concentrations of 8 ppb in summer and 19 ppb in winter . In three New Jersey facilities, Liang and Waldman also found NH3 concentrations to be higher indoors than outdoors. In a daycare facility the mean NH3 concentration was 61 ppb; in a nursing home, 56 ppb; and in a home for the elderly 31 ppb and 29 ppb .

For 24 homes in Uniontown, PA, Suh et al. reported a geometric mean indoor NH3 concentration of 22 ppb , much higher than the outdoor level of 0.3 ppb.In a study of 47 homes in State College, PA, Suh et al. obtained similar results: geometric mean = 20 ppb; GSD = 2.2.As expected, indoor NH3 concentrations tended to be higher in residences with lower air-exchange rates, albeit with considerable scatter. In Connecticut and Virginia, Leaderer et al. measured NH3 levels, in addition to other inorganic species, in 58 homes in the summer and 223 homes in the winter. During the summer, mean NH3 levels were 32 ppb in air-conditioned homes and 28 ppb in homes without AC. During the winter, mean NH3 levels were 44 ppb in homes with kerosene heaters and 38 ppb in homes without. In 10 Albuquerque homes, known to have elevated levels of nitrogen dioxide, mean NH3 concentrations were 20 ppb.Recently, Ampollini et al. reported time-resolved NH3 concentrations, measured with a cavity ring-down spectrometer in a test house in Austin, Texas, during the HOMEChem campaign.During unoccupied periods, the mean NH3 concentration was 32 ppb, increasing when indoor temperature increased. During high-occupancy events, the mean concentration was 52 ppb. Levels rose to an average of 62 ppb while cooking a turkey, and 73 ppb while cleaning with an ammonia-based product.When the air conditioning cooling coil cycled on, the NH3 concentration dropped,plant benches qualitatively consistent with expectations for two influencing factors: dissolution of NH3 in water on coils and lower emission rates at lower temperatures. A half hour of venting with outdoor air substantially reduced the indoor NH3 concentration, but it returned to its prior concentration in less than an hour after the venting ended. The return to concentrations before venting was confirmed during five separate venting periods on a day dedicated to such experiments. These results suggest the presence of a large reservoir of sorbed and/or dissolved NH3 associated with exposed indoor surfaces in the test house. It is instructive to compare the values in Table 6 for indoor NH3 concentrations with calculated estimates based on whole-body emission rates. Assuming no loss of indoor NH3 other than by ventilation and using Li et al.’s average whole-body emission rate at moderate temperatures of approximately 1 mg h-1 person-1 in a residence ventilated at 5 L s-1 person-1 , the calculated NH3 concentration would be about 80 ppb. This is higher than all of the reported mean indoor concentrations in Table 6, suggesting that loss of NH3 from indoor air by processes other than ventilation is an important fate.

Deposition to indoor surfaces is supported by observations made after cleaning with an ammonia-based product in the HOME Chem experiments. After reaching its peak concentration, ammonia levels decreased at a rate substantially faster than the air-exchange rate. In summary, in occupied buildings measured indoor NH3 concentrations are typically in the range 15-75 ppb and are much higher than outdoor concentrations. Indoor enhancement is consistent with strong NH3 emissions from occupants. Higher concentrations occur when other sources are present .In bulk condensed water, in aqueous atmospheric aerosols, and in aqueous surface films, NH3 equilibrates with the ammonium ion . Outdoors, as SO2 is oxidized to H2SO4, gasphase ammonia partially neutralizes H2SO4, forming ammonium salts, e.g., 2SO4, HSO4, and 3H2. The dominant ammonium salt depends on the relative amounts of NH3 and H2SO4 and is also influenced by the presence of nitric acid. Ammonium sulfate salts are often the most abundant inorganic constituent of fine-mode particles. In regions with high levels of nitrogen oxides, aerosol ammonium nitrate levels can approach or exceed those of ammonium sulfate salts. Indoors, ammonium is a common counterion for sulfate, nitrate, and chloride salts present in airborne particles and settled dust. Indoor sources of ammonium include outdoor-to-indoor transport of particles and generation indoors by the reaction of ammonia with acidic species . Many of the studies that have measured indoor ammonia concentrations have also measured ammonium concentrations in indoor airborne particles, commonly reporting results in terms of nmol of ammonium per m3 of air. Table 7 summarizes such measurements in selected studies, contrasting indoor and outdoor values. Sinclair et al. measured NH4 + in fine- and coarse-mode indoor and outdoor particles for extended periods at sparsely occupied telephone switching offices in Wichita KS, Lubbock TX, Newark NJ and Neenah WI. Ammonium was present primarily in fine-mode particles. These offices were mechanically ventilated and HVAC systems contained particle filters, which removed some of the particles from the ventilation air. Consequently, the I/O ratios for fine-mode ammonium were low, ranging from 0.065 to 0.20 , depending on the removal efficiency of the filters at a given facility.The low I/O ratios translate to low indoor NH4 + concentrations in fine-mode particles, ranging from mean values of 0.13 µg/m3 in Lubbock to 0.26 µg/m3 in Wichita. Li and Harrison measured much higher ammonium levels in indoor aerosol particles in university buildings,finding a mean value of 2.44 µg/m3 and an average I/O ratio of 0.96. These higher values are reasonable, given that they were measured in a communal kitchen, coffee room, and corridors, whereas the measurements by Sinclair et al. were in offices with filtered ventilation air. Although Li and Harrison found no correlation between indoor and outdoor NH3 levels, they did find significant correlation between indoor and outdoor NH4 + levels, indicating the importance of outdoor-to-indoor transport as a source of indoor particle-phase ammonium.Based on measurements made in five Los Angeles area museums, Ligocki et al. observed that the indoor/outdoor ratios for NH4 + in fine particles was always less than one and tended to be higher in summer compared to winter. A linear regression model indicated significant correlation between indoor and outdoor levels for fine-mode NH4 + . The ion balances for the aerosol samples indicated that ammonium was primarily associated with sulfate in the summer and with nitrate in the winter. In a study of Boston homes, Brauer et al. found that mean ammonium levels were higher in summer than in winter. In both seasons, the I/O ratio was close to unity. In the New Jersey institutional buildings sampled by Liang and Waldman, I/O ratios for fine-particle NH4 + ranged from 0.44 to 1.1, with median indoor concentrations in the range 73-117 nmol/m3 . Suh et al. measured indoor and outdoor levels of fine-particle ammonium in the homes of 24 children in Uniontown, PA.

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Humidity may play a role in sensory perception of indoor environmental quality

Novel medications and novel biological targets call for careful assessment of mechanisms beyond the “usual suspects”, such as changes in mean levels of subjective response and alcohol craving. Ultimately, the combination of multiple scientific approaches, including human laboratory, DDAs, neuroimaging, and biomarker assessment, offer complementary and clinically useful findings that can inform the development of ibudilast, and immune treatments for AUD more broadly. The chemical composition of indoor air influences its healthfulness as well as its suitability for preserving cultural artifacts and protecting sensitive electronic equipment. As measurement technologies have improved, our understanding of the complexity of indoor air has grown. A striking feature of the atmosphere in general and of indoor environments in particular is the steep increase in the number of chemical species of potential interest as the minimum quantifiable concentration diminishes. In the atmosphere, the number of chemical species present at a level of 0.1% or higher is only four: N2, O2, Ar, and H2O. Decreasing the minimum level of concern to one part per million adds only a few components, such as CO2 and CH4. However, when the threshold for concern is set at a part per billion or a part per trillion, the number of constituents rises to hundreds or thousands of species. These numerous species exhibit a broad range of chemical properties and pose diverse health-risk and material-damage concerns. Even at relatively low fractional abundance, some chemical components may significantly influence the attributes of indoor air. Thinking about the vast number of molecules in a given macroscopic air volume can help to establish perspective. Consider, for example,marijuana grow system that adults inhale an average of 15 m3 or about 600 moles of air daily. This daily quantity of inhaled air corresponds to almost 4 ´ 1026 molecules.

Even at the small fractional abundance of one part per trillion, the daily number of molecules of a trace species inhaled could be nearly 400 trillion. In part because of the large number of compounds of potential interest, it is scientifically valuable to categorize species according to key properties. One prominent example is the grouping of organic compounds into categories based on volatility, i.e., very volatile organic compounds, volatile organic compounds, and semivolatile organic compounds. 1 Such a grouping allows for more efficient identification and treatment of important physicochemical processes governing the sources, dynamic behavior, and fates of indoor-air constituents than would be possible using a purely chemical-by-chemical approach. This review is concerned with two broad and interrelated categories of chemicals occurring in indoor environments: acids and bases. We are guided principally by the Brønsted-Lowry conceptualization, in which a key feature of an acid is its tendency to donate a proton when in aqueous solution; the key complementary feature of a base is to accept a proton. The review’s scope is specifically restricted to compounds that can be found in indoor air, considering gaseous species and also species primarily associated with airborne particles. The review aims to be thorough but does not aspire to be comprehensive. We do intend to include all major classes of acids and bases that occur indoors with substantial exploration of specific examples within these major classes. The indoor environments of concern are those that are normally occupied and of the types in which people spend much time, including but not limited to residences, schools, and offices. As much as possible, our review approach is strongly grounded in physical science and aims to be incisively critical. We synthesize and report measured concentrations. We are particularly interested in processes that govern such concentrations, including characterizing sources and associated emission rates; factors influencing the dynamic behavior; fates; and consequences.

Depending on the relative abundance of condensed-phase water indoors and key physicochemical properties of the chemical compounds, aqueous-phase processes can strongly influence the airborne concentrations of acids and bases indoors as well as altering the pH of indoor water. Although there is a deep and extensive history of interest in indoor acids and bases, until now there has not been a systematic and thorough review of the state-of-knowledge for these important chemical classes. As early as the 1850s, Max von Pettenkofer used indoor abundance of carbonic acid to determine the level of ventilation required to achieve good indoor air. In the middle of the 20th century, sulfur dioxide emerged as an important urban air pollutant, and studies were undertaken to better understand the extent of protection provided by being indoors. Later, as urban and regional air pollution concerns began to focus on particulate matter, a specific interest emerged in the role of aerosol strong acidity as a potential cause of adverse health effects. Several studies were undertaken in the late 1980s and 1990s to better understand indoor concentrations and associated exposures of acidic aerosols. 5,6 Long-term awareness that acidic pollutants can damage cultural and historic materials has been documented by Baer and Banks. Corrosion of metals in indoor environments in relation to acid gases and other pollutants was already studied in the early 1970s.During the past decade, strong new research interest has emerged concerning indoor acids and bases. One dimension has been some evidence, although not yet conclusive, that exposure to excessive carbon dioxide levels indoors can impair cognitive performance. This concern is but one example of a broad array of issues regarding how occupants influence indoor air quality, including through the acidic and basic species they generate, such as the fatty acids in skin oils. Following parallel advances in outdoor atmospheric chemistry, a new area of focus indoors is the class of compounds that are water soluble organic gases, of which acids are a major subcategory. In addition, instruments that have advanced the study of outdoor atmospheric chemistry are now beginning to be applied indoors.

Advanced technologies, such as high-resolution time-of-flight chemical ionization mass spectrometry , aerosol mass spectrometry , and semivolatile thermal-desorption aerosol gas chromatography are permitting new aspects of indoor air quality to be probed, reflecting their capabilities for sensitive measurement with fast time response combined with strong levels of chemical specificity. Recently published studies with such instruments are providing new insights in many aspects of indoor air quality, including the sources, abundances, and dynamic behaviors of indoor acids and bases. The body of this review is divided into three main sections. The first considers water in indoor environments. An important topic in its own regard, only certain aspects of indoor water have been well-addressed in prior studies. For this review, it is an important subject because of the strong two-way interactions between condensed-phase water and airborne acids and bases: acid and base uptake influence the pH of liquid water, a “master variable” of water chemistry; partitioning into the condensed phase alters the airborne concentrations and fates of airborne acids and bases; and condensed-phase water can serve as a large reservoir for acids and bases,cannabis vertical farming buffering their airborne concentrations. Because of water’s important role influencing indoor acids and bases, we review the state of knowledge across a range of physicochemical forms: water vapor, bulk liquid water, sorbed water, water in surface films, and water in suspended airborne particles. The middle section of the article explicitly addresses indoor acids and bases. Acknowledging the richness of the subject and the diversity of the species involved, the material is presented in ten subsections, respectively addressing carbon dioxide, ammonia, sulfur dioxide and sulfate, nitric and nitrous acid, hydrochloric and hypochlorous acid, carboxylic acids, other organic acids, aerosol strong acidity, amines and amino acids, and nicotine. The final core section of the report is concerned with the roles of indoor surfaces and surface materials influencing the dynamic behavior, fates and consequences of indoor acids and bases. A prominent feature that contrasts indoor air from outdoor air is the high surface-to-volume ratio indoors, amplifying the importance of surface interactions influencing indoor air quality. With respect to indoor acids and bases, this feature is pertinent, extending beyond the roles of surfaces as substrates for aqueous and organic films and sorbents for water. Water is centrally important to the concentrations, fates and consequences of indoor acids and bases. When a molecule of a gaseous acid dissolves into condensed-phase water, it can release a proton, changing the pH of that water. The extent to which the acid or base undergoes a proton-exchange reaction depends on several key factors: the pH of the aqueous phase, which is influenced by the abundance of that particular species; the abundance and strengths of other acids and bases; the amount of condensed-phase water; the presence of other anions and cations ; and the influences of solid substrates in contact with the water.

The ionized form of the acid or base has negligible vapor pressure, and so will remain in the condensed phase while ionized. However, acid-base reactions are readily reversible, so a change in pH can lead to the reestablishment of the neutral form of the molecule, which may then return to the gas phase. Indoor water occurs in multiple forms; only some of these are well characterized. Gaseous water is abundant and can play a role in gas-phase chemistry; however, in the context of indoor acids and bases, it is more important as a source and sink for indoor water’s condensed phases. As a condensed species, several forms of water are potentially important in acid-base processes: bulk liquid water, sorbed water, aqueous surface films, and particle-phase water. These different forms of condensed-phase water can influence indoor acids and bases in different ways. In this section of the review, we summarize the state of knowledge about indoor water vapor along with each of these main forms of condensed-phase water. Water is an important component of indoor environmental quality for reasons that extend well beyond the concerns of acids and bases. Dampness and moisture are strongly related to adverse respiratory health symptoms and allergies. Influenza transmission may be influenced by humidity.Humidifiers are used to deliberately increase the water vapor content of indoor air; these have the potential to elevate pollutant exposures and health risks. In warm and humid climates, much of the energy for air conditioning is used to dehumidify ventilation air. The nature and abundance of indoor water varies among building types, across climate zones, and seasonally. In this section, we emphasize general principles and broadly relevant empirical evidence. When specificity is warranted, we consider conditions that are common in residences in the United States.This category includes all forms in contact with indoor air in which the water is sufficiently abundant to be visible. It also includes forms of water that are potentially visible, but normally hidden, such as in sink traps and toilet tanks. We know of no quantitative accounting of the abundance of bulk condensed water in residences or other indoor environments. Direct inspection of spaces occupied by the authors, along with some reflection, suggests that quantities of bulk liquid water in residences might commonly be in the range 0.35-35 L. In the event that all such water was fully equilibrated with gaseous acids and bases, and if such an abundance were present in a 350 m3 residence, then the corresponding contribution to the liquid water volume ratio would be in the range L* = 0.001 – 0.1 L m-3 . Although anecdotal and therefore not directly generalizable, it seems worthwhile to make a brief account of the bulk water observed at a moment in time in the home of one of the authors. In the kitchen, there is about 2 L of visible liquid water, divided among 1 L used to soak dried beans for an upcoming meal, 0.2 L in a teakettle, 0.1 L in a drinking glass, and 0.5 L in an automatic coffee maker. There are smaller amounts of water associated with washed breakfast dishes on a drying rack, dish towels, and the wetted surfaces of the kitchen sink. There is also ~0.25 L of water in a P-trap beneath the kitchen sink. If 2 L of water were fully equilibrated with the kitchen volume of about 50 m3, the corresponding contribution to L* would be 0.04 L/m3 . Each of the two bathrooms in this house has a toilet with about 1 L of water in the bowl and 5 L of water in the tank that provides for flushing. Each bathroom has a sink and a shower. Each of these contains a P-trap connected to the drain.

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There was no significant difference in the detection frequencies between mothers and children

The ELISA was performed using 96-well high binding micro titer plates coated with coating antigen cAg06 , washed with 10mM phosphate buffered saline + 0.05% Tween 20 , blocked with 0.5% bovine serum albumin in PBS. All standards, quality control samples and urine samples were prepared in 10% MeOH in PBS prior to the assay procedure. A 10-point calibration curve was prepared for each assay using a serial 1:5 dilution from the highest standard solution. A blank 0 ng/mL standard in the same 10% MeOH/PBS solution was also prepared. Wells containing instrument blanks received a 50 uL aliquot of PBST, while all remaining wells received a 50 uL aliquot of anti-rabbit 3PBA antibody #294 diluted 1:7000 in PBST. The goat anti-rabbit IgG-horseradish peroxidase conjugate was diluted 1:3000 in PBST. The substrate solution in dimethylsulfoxide per 25 mL of acetate buffer, pH 5.5 was added and color development was stopped after 15 min with 2 M H2SO4. The absorbance was measured using a Vmax micro plate reader in dual wavelength mode at 450 nm – 650 nm. Urinary creatinine concentrations were determined using the methods described in Ahn et al. 2011 .All urine samples, blank samples and QC samples were analyzed in triplicate. The final concentrations were calculated from the means of the triplicate values. If one of the triplicate values fell below the LOD it was not considered in the calculation of the mean concentration. Mean values that fell between the LOD and the LOQ were retained in all further statistical analyses. For each set of extractions,horticulture rack one urine sample was randomly chosen for QC analysis and was spiked to a level of 10 ng/mL 3PBA before extraction in order to verify that there were no matrix effects from the sample extract and to check method accuracy. Five different urine samples were also extracted and analyzed in duplicate at different time points in the analysis to verify the method precision.

For further validation of the ELISA method, and in order to try to quantify any cross reactivity that may have occurred, a set of six urine samples was sent to Emory University in Atlanta, GA where they were analyzed by high performance liquid chromatography-tandem mass spectrometry using a well established method .Summary statistics for both the volume based and creatinine adjusted 3PBA data were calculated. For concentrations below the limit of detection , an imputed value was assigned equal to the LOD divided by the square root of 2 . To determine predictive variables from the questionnaire data to include in a multivariate analysis, linear regression with both the log-transformed creatinine concentration and the variable of interest, referred to as the bivariate comparisons, were performed for each variable with 3PBA concentration. For each type of pesticide application, we created a continuous variable that represented the number of applications per year as well as a categorical variable indicating if that type of pesticide had been applied. Additional variables were also created summing pesticide applications across different application types. Food diaries were translated to English, and individual food items were grouped into ten different food categories: Fruit, Vegetables, Legumes, Meats, Snack/Processed Foods, Dairy, Beverages, Grains, Mixed Foods , and Other. Each category also had subcategories for specific, popular food items. For example, in the Dairy category, subcategories included Milk, Cheese and Other Dairy. Two variables were created for each food category and sub-category. First a categorical variable that indicated if the participant had consumed an item from a given category or sub-category. Second, a continuous variable was created with the number of servings in each category or sub-category. Volume based 3PBA concentrations were log-transformed to better approximate a normal distribution and regressed against the log-transformed creatinine concentrations and the individual questionnaire variable . Two regression analyses were conducted for each variable, one including only data from the mothers and one including only data from the children . There were a number of variables related to individual measures of home disrepair that were significant in the bivariate analysis. Because many of these measures of disrepair were correlated, item analysis was performed to select and evaluate the internal consistency of a set of items for a summative scale score.

The resulting Home Disrepair Score is computed by summing the water damage, leaks, carpet damage, worn spots or holes in the counters and rotten wood indicators and has good internal consistency in our sample . Multivariate regression was then performed to evaluate which questionnaire variables were most predictive of the urinary 3PBA concentrations. Three models were fit, one with the data from both the mothers and the children, one with data only from the children, and one with data only from the mothers. As an alternative, we also ran the models using the metabolite concentrations directly adjusted by the creatinine concentration. All statistical analyses were performed using SAS version 9.2 .The resulting Home Disrepair Score is computed by summing the water damage, leaks, carpet damage, worn spots or holes in the counters and rotten wood indicators and has good internal consistency in our sample . Multivariate regression was then performed to evaluate which questionnaire variables were most predictive of the urinary 3PBA concentrations. Three models were fit, one with the data from both the mothers and the children, one with data only from the children, and one with data only from the mothers. As an alternative, we also ran the models using the metabolite concentrations directly adjusted by the creatinine concentration. All statistical analyses were performed using SAS version 9.2 .Women in this study ranged in age from 23 to 51 years old; they had very low educational levels, with 46% having only a 6th grade education or lower; they were almost all married and lived in homes with 4 or more residents . Pest problems were common with 59% reporting insect problems, 43% using pesticides indoors and 35% applying pesticides outside . A Spearman rank correlation analysis was performed to see if there were associations between the two measures of home disrepair with pesticide application. Multiple significant correlations were observed , suggesting that poor housing conditions do lead to higher rates of pesticide application. For each set of three triplicates, the sample standard deviation of the urinary 3PBA concentration was computed. The average 3PBA concentration was 2.51 with an average standard deviation of 0.42 ng/mL. Less than 10% of the samples had a triplicate that fell below the LOD resulting in that value being dropped from the calculation of the mean.

Recoveries of the fortified urine samples ranged from 67 to 111% with an average of 82 ± 12%. The LOD of this analysis was estimated to be 0.1 ng of 3PBA in 1 mL urine. The limit of quantitation was determined to be 2 ng/mL. The percent difference between concentrations in duplicate aliquots of selective urine samples ranged from 3.6 to 28% with an average of 14%. Six urine samples were also analyzed by HPLC-MS/MS to further validate the ELISA method. The square of the correlation coefficient between the 3PBA concentrations from the two laboratory methods for the six samples tested was R2 = 0.934, and the %D ranged from 7.9 to 30.6% with an average of 25%, with the ELISA resulting in higher concentrations in four of the samples, and lower concentrations in two of the samples. Urinary 3PBA concentrations in our study were detected in 80% of all samples with a range of 0.3–13 ng/mL .However, adjustment for urinary creatinine resulted in a significantly higher concentration of urinary metabolites in children than in mothers . We calculated the correlation of urinary 3PBA concentrations between mothers and children. Urinary 3PBA concentrations from mothers and children in the same household were positively correlated for both volume based and creatinine adjusted concentrations .Variables included in the multivariate analysis were based upon the results of the bivariate analysis. The Home Disrepair Score, derived from the combination of multiple questionnaire items,vertical grow system was significant in the bivariate analysis only for mothers, while the Inside Housing Conditions score, derived from the staff evaluation during the MICASA follow-up interview, was significant only for the children. Because these two scores were designed to measure similar housing characteristics, both scores along with the Outdoor Spray pesticide use variable from the MICASA baseline questionnaire and the log-transformed creatinine concentrations were included in all three multivariate models described below. Multivariate models assessed factors associated with 3BPA concentrations in the combined sample , children only and mothers only . Both the Home Disrepair Score and Outdoor Spray were positive significant predictors of urinary 3PBA levels in the total study population model, which included logtransformed creatinine, the Home Disrepair Score, Outdoor Spray, Inside Housing Conditions and a Mother/Child variable .

The model restricted to children included food diary variables significant in the bivariate model: Apple , Milk , All Meat and Cereal as well as the log-transformed creatinine, the Home Disrepair Score, Outdoor Spray and Inside Housing Conditions. In this model Outdoor Spray and Inside Housing Conditions were marginally significant positive estimators of urinary 3PBA concentration. Cereal Total, while marginally significant, was negatively associated with urinary 3PBA in the children only data. In the mother only model we included the food diary variables Eggs , Beans , Grapes , Chicken , and Cereal as well as log-transformed creatinine, the Home Disrepair Score, Outdoor Spray and Inside Housing Conditions. The Home Disrepair Score , Outdoor Spray , and Cereal Total were all significant positive estimators of urinary 3PBA levels in the mothers. The models with the metabolite concentrations directly adjusted for creatinine resulted in similar associations .We assessed the exposure to pyrethroid pesticides in 105 women and 103 children in a farm worker population by laboratory measurements of the metabolite 3PBA in urine samples and by questionnaire data. This population had a relatively low educational level, with only about half of the adult women participating in our study reporting a 6th grade education or higher, in contrast to the 85% of U.S. adults who have a high school diploma . The results from the ELISA method used to analyze urinary 3PBA concentrations in this study were validated by a more traditional instrumental method at the Emory University in Atlanta, GA. The suitability of this newer analytical technique for use in biological monitoring of 3PBA is further corroborated by Chuang et al. who analyzed over 100 urine samples and showed high correlation between ELISA and GC/MS data, with the square of the linear correlation coefficient R2 = 0.906 and no significant between the two methods of analysis for any given sample . Children had higher concentrations of this metabolite than their mothers. This result is consistent with multiple pesticide exposure studies and most likely has to do with differences in behavior that leads to higher non-dietary ingestion in children . Once pyrethroid pesticides have entered the home, the carpets and cushioned furniture can act as repositories for pesticides . High levels of pesticides in carpet dust is a particular concern for young children who, due to their continual exploration of their environments, spend a large amount of time on the floor and have increased hand to mouth activity, resulting in increased exposure to the pollutants through dermal and non-dietary ingestion routes . The median concentrations in the National Health and Nutrition Examination Survey , a population based sample, collected from 1999 to 2000 were 0.30 and 0.26 ug/g creatinine for children and adults , respectively, and only increased slightly to 0.33 and 0.30 ug/g creatine for children and adults, respectively, in samples collected from 2001 to 2002 . Median urinary 3PBA concentrations of NHANES samples collected from 2007 to 2008 increased a bit more to 0.42 and 0.38 ug/g creatinine for children and adults, respectively . In the Children’s Total Exposure to Persistent Pesticides 2000 to 2001 study, a population based sample of preschool children living in Ohio, the median level was 0.32 ug/g creatinine for children aged 1–5 years . The 2004 Casa y Campo study, a community-based project aiming to reduce pesticide exposure among farm workers and their families in eastern North Carolina, reported median concentrations of 3PBA in children aged 1–6 years of 0.15 ug/g creatinine .

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Hepatitis C virus infection status was categorized as HCV negative if HCV antibody testing was negative

To the best of our knowledge, there has not been a published report that has followed HIV+ individuals and MSM longitudinally over an extended period to characterize the natural history of their marijuana use. Past studies on substance use patterns in these populations have often focused on alcohol or heavy episodic drinking, cigarette smoking or stimulant use. Therefore, the objectives of the current study are to characterize the longitudinal trajectories of marijuana use in a sample of HIV-seropositive and HIVseronegative MSM over a period of 29 years, and to identify factors associated with unique trajectories of marijuana use, as well as those that can change over time that may modify the course of the trajectory. The MACS study protocols were approved by the institutional review boards at the respective recruitment centers and their community affiliates and informed consent was obtained from all participants. MACS participants return every 6 months for a physical examination, collection of blood specimens and completion of a detailed interview and questionnaires. The interview and questionnaires include demographic, psychosocial, behavioral and medical history data. The questions about their recreational drug use, including marijuana, alcohol, poppers, cocaine, crack, heroin, methamphetamine, ecstasy, injection drug use as well as smoking history since their last visit were collected using Audio Computer Assisted Self-Interviewing , an approach previously demonstrated to provide more accurate assessments of ‘sensitive behaviors’ than interview-administered questionnaires among MSM. This analysis included data collected from standardized cannabis grow supplies use questions from semiannual study visits 1 through visit 59 . The study sample included 3658 participants who had data about marijuana use for at least 25 % of their possible study visits during the follow-up period. Specifically, the men enrolled in 1984–1985 and 1987–1991 had 15 and 13 visits or more respectively, whereas, the men enrolled in 2001–2003 had 6 or more visits.

The median years of follow-up was 11.5 years. Alcohol Use—Using data regarding frequency of drinking and average number of alcoholic drinks, alcohol consumption at baseline and at each study visit was categorized as hazardous drinking, low or moderate use or no alcohol use. Tobacco Use—Participants were classified as never, former and current smokers of cigarettes at each study visit. Participants were asked two questions including: whether they ever smoked cigarettes and whether they smoke cigarettes now. Participants were considered to be current smokers if they responded ‘Yes’ to both questions. Participants were categorized as former smokers if they answered ‘Yes’ to ever smoking cigarettes and ‘No’ to the smoking cigarettes now. Never smokers included participants who answered ‘No’ to both questions. In addition, among current smokers, pack-years of smoking at initial visit and at each subsequent visit was calculated using participants’ responses to questions about the number of packs of cigarettes smoked per day. Stimulant/Recreational Drug Use—Participants were considered to be users of stimulant drugs if they reported the use of any of the following drugs at baseline and at each study visit: crack cocaine, other forms of cocaine, methamphetamines , other recreational drugs such as “ecstasy” or MDMA . Clinical Factors—HIV serostatus was assessed using an enzyme-linked immunosorbent assay with confirmatory Western blot tests on all MACS participants at each participant’s initial visit and at each study visit for participants who were initially HIV−. Standardized flow cytometry was used to quantify CD4 + T-lymphocyte subset levels by each MACS site and categorized as ≤200/mm3 , 201–500/mm3 , and >500/mm3 . Levels of plasma HIV RNA were measured using either the standard reverse transcription-polymerase chain reaction assay or with the Roche ultrasensitive assay were used to create a dichotomous variable to denote detectable versus undetectable viral load. Participants were classified at each MACS study visit as HCV positive if they were found to be in the process of seroconversion, acute infection, chronic infection, clearing , or previously HCV positive, but now clear of HCV RNA.

In addition to the aforementioned covariates, we considered that the trajectories of marijuana use over time among HIV+ participants may be influenced by factors specific to HIV-infection. ART use was dichotomized as use of any ART since the last study visit versus no therapy used. Attrition—Two binary variables were constructed and used as covariates to adjust for the effect of attrition: one for participants who dropped out or were lost to follow up and the other for those who died within the follow-up period .We used participant’s self-reported frequency of marijuana use across the follow-up period to identify trajectories using a semi-parametric group-based mixture model: PROC TRAJ SAS procedure. This approach sorts each participant’s frequency of marijuana use over their follow-up period into ‘clusters’ and estimates a single model—consisting of distinct trajectories. The procedure calculates the probability of each participant belonging to each trajectory group and assigns individuals into trajectories based on their highest probability of trajectory membership. Participants were followed from the time of enrollment until either the time of death, lost to follow up or until the end of the study period . We began by fitting a series of models with two to five trajectories by assuming linear, quadratic and cubic shape of the trajectory group curves. Several factors were considered in determining model fit and the optimal number of trajectory groups that best represented the heterogeneity of groups within the data: including, a priori knowledge from previous research on trajectories of marijuana use, model fit statistics including Bayesian information criterion, Akaike Information Criterion, average posterior probability of group membership, significance of the shape of the trajectory group curves , and size of the group membership . Model fitting was an iterative process, starting with a quadratic specification for the shape of the trajectory group curves and assessing whether an additional group resulted in a better model fit based on the aforementioned criteria.

We then estimated higher order shapes of the trajectory group curves and subsequently dropped non-significant terms. Models used a zeroinflated Poisson distribution to account for the large number of participants who reported not using marijuana. After the optimal number of trajectory groups and shape of trajectory change were selected, we included covariates of interest to the trajectory models. For this analysis, two types of covariates were considered: time-fixed/risk factors of trajectory group membership and time varying covariates. These time-fixed/risk factors comprise characteristics established before or at the time of the initial period of trajectories that may serve to predict membership in a given trajectory. Time-varying covariates measured during the course of the trajectory provide trajectory group-specific estimates of whether these covariates alter the course of the trajectory. One advantage of the PROC TRAJ software is that it allows for joint estimation of the parameters that describe the shape of the trajectory group curves,cannabis grow facility adjusted odds ratio and the coefficient estimates . We estimated models for all participants as well as by HIV serostatus. The analysis of all participants was adjusted for sociodemographic characteristics, depressive symptoms, substance use variables, hepatitis C infection status, attrition variables, and HIV serostatus. To account for potential differences in marijuana use by geographic region/site and MACS enrollment cohort, all models included variables for MACS center and enrollment cohort. In the analysis restricted to HIV+ participants, we included other clinical factors relevant to HIV+ status such as ART use, CD4 counts, and viral load detectability. All analysis was performed in SAS 9.4 . The 3658 participants in this study contributed a total of 105,595 person-visits; the median number of visits was 23 representing approximately 11 years . Among those who were HIV+ , the mean age at baseline visit was 35 years [standard deviation = 7.7], median number of visits was 23 , the majority were non-Hispanic whites and 24 % were non-Hispanic blacks . At baseline, among the HIV+ participants, marijuana use was high , 90 % used alcohol , 67 % reported stimulant/recreational drug use, 44 % were current smokers and 29 % were classified as having clinically significant depressive symptoms . At baseline, the HIV− participants in this study reported lower marijuana use , stimulant/recreational drug use , rates of current smoking and depressive symptoms than the HIV+ participants. Both groups were similar with regard to alcohol use . Marijuana Trajectories—Using data for the entire sample, participants’ self-reported frequency of marijuana use across the follow-up period identified four groups with distinct trajectories of marijuana use. We chose a four-group solution based on model parsimony, interpretability of trajectories, BIC and AIC values, significance of the polynomial growth terms, average posterior probabilities and trajectory group size membership . Model fit information and average posterior probabilities of all models are displayed in supplemental Tables 2 to 5. Figure 1 displays the trajectories of marijuana use of these four groups, which we labelled as: “Abstainer/Infrequent”, “Decreasers”, “Increasers” and “Chronic high” trajectory groups.

The abstainer or infrequent use group was characterized by a group of men who abstained from or infrequently used marijuana during the follow-up period. The decreaser group consisted of a group of men who reduced their marijuana use from nearly weekly use to infrequent use over the follow-up period. The increaser group comprised a group of men who initially decreased their marijuana use during the first 10 years of follow-up, after which they began to increase their use over time. The chronic high group represents a group of men who persistently used marijuana nearly daily over the follow-up period. Figure 2 displays trajectories of marijuana use among HIV+ participants: 61 % were in the abstainer/ infrequent use group, 14 % were in the decreaser group, 14 % in the increaser group, and 11 % in the chronic high group. Table 2 displays the baseline characteristics of the entire sample by the four identified trajectory groups. The median number of visits was lower among those in the increaser trajectory group. Participants in the abstainer/infrequent use group were older at baseline compared to the other groups. Frequency of marijuana use at baseline varied across the marijuana trajectory groups: as the proportion of daily users were < 1 % in the abstainer/ infrequent, 3 % in the decreasers, 10 % in the increasers, and 54 % in the chronic high groups. Racial status , detectable HIV viral load and CD4 counts were similar across the marijuana trajectory groups. This study utilized data from the MACS cohort to assess different patterns of marijuana use and to examine both risk factors and time-varying correlates associated with the different trajectories of marijuana use. Our analysis revealed that MSM in the MACS exhibited four distinct trajectories of marijuana use over time, including: abstainer/infrequent, decreasers, increasers and chronic high groups. Most of the men in this cohort displayed a pattern of abstaining or infrequent use over time whereas approximately 10 % who used daily or near daily at their index visit continued this pattern of use over their follow-up visits. About a quarter of the men changed their pattern of use over time, either decreasing or increasing use . Overall, our analysis suggested that these patterns of marijuana use over time were similar for both HIV+ and HIV− participants. In the analysis among all men, HIV+ status was associated with membership across all three trajectory groups reporting any marijuana use. Among HIV+ participants, having a detectable HIV RNA over time was associated with increasing marijuana use only among the men who increased their marijuana use during the follow-up period. Self-reported ART use over time in HIV+ men was associated with reducing marijuana use in the abstainer/ infrequent and increaser groups. Overall, alcohol consumption, cigarette, stimulant/ recreational drug use and IDU over time were associated with increasing marijuana use in nearly all trajectory groups. To the best of our knowledge, we are not aware of any previous study that has examined trajectories of marijuana use among HIV+ and HIV− MSM over a long period of follow-up. Prior studies that have assessed trajectories of marijuana use have focused on adolescents transitioning into young adulthood or racial/ethnic minorities, with a few studies reporting trajectories of use covering adulthood. Direct comparisons of the results from our study with prior research may not be straightforward due to the different populations studied and age periods covered. However, nearly all studies on trajectories of marijuana use have identified a group that abstained or used infrequently, with some identifying a chronic high user group and a few identifying groups that increased and decreased their use.

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Prospective studies have also demonstrated an increased risk of ARDS among smokers

In 2014, PM less than 10 mm in diameter and less than 2.5 mm in diameter accounted for at least 3 million deaths and 85 disability-adjusted life years, primarily because of impacts on chronic cardiovascular and pulmonary conditions.Recently, air pollution in the United States has begun increasing for the first time since 2016 .Ambient pollution is a risk factor not only for the development or worsening of chronic illnesses but also for acute illness. For example, a case control study of older adults in Canada found that long-term exposure to PM 2.5 and NO2 was independently associated with an increased risk of hospitalization for community-acquired pneumonia.Short-term exposure to increasing levels of PM 2.5 was also shown to increase the risk of hospital admission for cardiac and respiratory disease in the United States.Several recent studies have demonstrated that exposure to even low to moderate levels of ambient pollutants increases the risk of developing ARDS. In a prospectively enrolled cohort of patients with ARDS in the Southeastern United States, long-term ozone exposure was associated with the development of ARDS in a dose-dependent manner.This association was most pronounced among patients with trauma as their primary risk factor. Although the association between ozone exposure and the development of ARDS remained significant when controlling for potential confounders including smoking status, there was a statistically significant interaction between ozone exposure and smoking. When patients were stratified by smoking status, ozone exposure remained significantly associated with ARDS only among smokers. The investigators concluded that cigarette smoking likely potentiates the risk from ozone exposure.A subsequent study of patients from a prospectively enrolled cohort in Philadelphia further investigated the relationship between exposure to pollutants and ARDS development among patients with trauma.This study analyzed exposure to low to moderate levels of ozone, NO2, SO2, PM 2.5, and carbon monoxide . Long-term exposure to each of the pollutants was independently associated with an increased odds of developing ARDS. Furthermore,growing tables even 6 weeks of exposure to NO2, SO2, and PM 2.5 increased the odds of developing ARDS.

Differences between the findings of the 2 studies might be accounted for by regional variation in levels of pollutants and air quality monitoring and by the shared risk factor of the population in the second study. Together these studies suggest that exposure to ambient pollution even at low to moderate levels for time periods as short as 6 weeks increases the risk of ARDS. Large epidemiologic studies have also found associations between exposure to ambient pollution and an increased risk of developing ARDS. An observational study of more than 1 million hospitalizations between the years 2000 and 2012 among Medicare beneficiaries who developed ARDS used advanced modeling drawing on multiple data sources to predict average annual levels of ambient pollution across more than 30,000 zip codes.The investigators found that the rate of ARDS hospitalizations increased with increasing levels of both PM 2.5 and ozone. These findings were consistent even in regions where pollutant levels were within national air quality standards. The effect of PM 2.5 was most pronounced among patients whose primary risk factor was sepsis. Ozone exposure had the greatest effect among patients with pneumonia or trauma as their primary risk factor. Although fully accounting for confounding factors in observational studies can be difficult, results were similar in a propensity matched analysis that included variables such as demographic variations and percent of ever-smokers.The results of this large study demonstrate that the association between ambient pollution and ARDS is present outside of the trauma population in patients who are older with comorbid conditions. Another retrospective cohort study of more than 90,000 patients found that increases in average annual PM 2.5 and ozone concentrations independently increased the odds of death from ARDS, suggesting that ambient pollution impacts not only ARDS incidence but also its outcomes.High levels of ambient pollution have also been associated with incidence and adverse outcomes in the coronavirus disease 2019 pandemic, although further studies in this area are needed.

The preponderance of the literature examining the connection between ARDS and ambient pollution has revealed an association between long-term rather than short term exposure to pollutants and ARDS incidence and outcomes. For example, the investigators who found a link between long-term ozone exposure and ARDS did not find the same association for 3-day exposure to environmental pollutants.However, one study from Guangzhou, China, demonstrated an association between short-term PM exposure and incident ARDS.This association may be related to the exceptionally poor air quality of the region in contrast to the other studies, which focused on settings with low to moderate levels of pollutants. There is some evidence, however, that short-term exposure to low levels of ambient pollution is associated with adverse pulmonary outcomes in critically ill patients. A study from Antwerp, Belgium—an area with historically low levels of ambient pollution—found that short-term pollution exposure was associated with longer mechanical ventilation.This study included a broad range of critically ill patients, some of whom did not have ARDS, but does suggest that a deleterious effect from short-term pollution exposure is not limited to areas with exceptionally poor air quality. Various underlying biological mechanisms may explain the basis for the relationship between environmental pollution and ARDS. A meta-analysis of exposure studies in healthy volunteers found that ozone increases the number of bronchoalveolar lavage neutrophils,which are implicated in ARDS pathogenesis.Ozone exposure also increased total protein levels in this analysis,reflecting loss of alveolar epithelial/endothelial barrier integrity.Many components of air pollution exert deleterious effects on pulmonary surfactant.Urban air particles directly stimulate an inflammatory response by pulmonary macrophages in vitro.PM has also been shown to increase markers of apoptosis, oxidative stress, and inflammation and to directly cause lung injury in mouse models.In humans, increased PM 2.5 levels are associated with circulating markers of endothelial injury,which is one of the key pathophysiological mechanisms in the development of ARDS.Although environmental pollutants alone may not be sufficient to induce severe pulmonary injury in humans, they likely increase susceptibility to other causes of ARDS such as respiratory infection and prime the alveolus for damage in these settings.

Wildfire smoke is an increasingly prevalent source of environmental pollution. Climate change has led to more frequent wildfires over a longer season.In the United States, PM air quality has improved over the past 3 decades except in areas that are prone to wildfires.Wildfires are associated with acute increases in ozone and PM as well as other pollutants such as volatile organic compounds.As noted earlier, previous studies of the relationship between ambient pollution and ARDS have generally focused on the average exposure in various regions over time, rather than on events that might be expected to acutely increase ambient pollution. In addition, smoke from wildfires may have chemical properties that make its risk profile different from that of PM or smoke from other sources.Although it is clear that wildfire-related pollution contributes to increased respiratory morbidity and health utilization overall,the specific relationship between ARDS and exposure to pollutants generated by wildfire smoke has not been studied . In vitro evidence demonstrates that wood smoke exposure diminishes alveolar barrier function and increases alveolar endothelial oxidative stress and apoptosis.In mice, PM collected during wildfires induced a more pro-inflammatory response and greater oxidative stress than ambient PM collected in the absence of wildfires.Wood fire smoke exposure has also been shown to induce a pulmonary and systemic inflammatory response in healthy volunteers.It is mechanistically plausible that the increased inflammation,grow tables 4×8 oxidative stress, and lung micro-vascular permeability in response to wood fire smoke demonstrated under experimental conditions would translate to an increased risk of ARDS. Future research should test whether ARDS incidence and outcomes change during or after wildfire events.The link between cigarette smoke and adverse health outcomes is well established, and reducing cigarette use has been a major focus of public health efforts over the past half century.Although rates of tobacco smoking have generally declined globally, they remain unacceptably high, and cigarette smoking is a leading cause of avoidable death. For example, the 2015 Global Burden of Disease Study found that approximately 11% of women and 14% of men in the United States report daily smoking and that smoking accounted for 6.4 million deaths globally.Alternative tobacco and nicotine delivery systems such as electronic cigarettes , or vapes, are increasingly popular, an especially concerning trend among children and adolescents.Although their long-term health consequences are not well established, e-cigarettes cause a specific lung injury syndrome, e-cigarette- or vaping-associated lung injury .E-cigarettes will be discussed in detail in a separate section. Although some retrospective studies have not found an association between cigarette smoking and ARDS,many studies demonstrate that both active smoking and passive cigarette smoke exposure are associated with ARDS, especially among certain clinical populations. Importantly, this association is independent of alcohol use, which is frequently associated with smoking and is a known risk factor for ARDS.A retrospective cohort study of patients in Northern California found that ARDS was more common among self-reported smokers in a dose-dependent manner. The investigators estimated that smoking carried an attributable risk in ARDS of 50%.A 2014 study of 381 patients with ARDS previously enrolled in randomized clinical trials examined the relationship between tobacco exposure and ARDS.Rather than relying on patient or surrogate reports, which lack sensitivity when compared with biomarkers for tobacco exposure,urine levels of NNAL -1–1-butanol were used to determine smoking history. The rate of active smoking among patients with ARDS in this study was significantly higher than the population average .

Smokers were younger and had fewer comorbidities than nonsmokers despite similar ARDS severity. Although unadjusted mortality among smokers was significantly lower than in nonsmokers, there was no significant difference after adjusting for comorbidities and severity of illness,suggesting that smokers develop ARDS when their illness is less severe than that of otherwise similar patients. Current cigarette smoking conferred increased odds for the development of transfusion-related acute lung injury in a two center prospective case-control study.Donor smoking history increased the odds of grade 3 primary graft dysfunction in a multi-center prospectively enrolled cohort of lung transplant recipients.A prospective study of the association between tobacco exposure and the development of ALI after blunt trauma used plasma levels of cotinine to differentiate between active and passive smoke exposure and to quantify exposure levels.Active smokers and passively exposed patients in this cohort from a single level 1 trauma center had similarly increased odds of developing ARDS independent of confounding factors, including alcohol use and trauma severity. Higher levels of plasma cotinine were associated with higher odds of developing ARDS.Another prospective study of patients with trauma enrolled between 2005 and 2015 confirmed that cigarette smoke exposure remains an important risk factor for ARDS and highlighted a particularly elevated risk among passive smokers in later years.In patients with trauma, impaired platelet aggregation likely mediates at least part of the effect of cigarette smoke exposure on ARDS risk.In addition, cigarette smoke alters the microbiota in patients with trauma such that their pulmonary microbiome is enriched for specific pathologic bacteria that are associated with ARDS development.In a prospectively enrolled cohort with diverse predisposing risk factors for ARDS, active cigarette smoking both by self-report and urine NNAL was associated with an increased odds of ARDS among patients with non-pulmonary sepsis as their primary predisposing risk factor.Patients with trauma and transfusion as their primary risk factor were not included in this study because of the previously established link between smoking and ARDS in these populations. Again, the mortality rate of active smokers was lower in an unadjusted analysis, but mortality was similar after adjusting for baseline severity of illness.This finding is consistent with the previous one that smokers are at increased risk of developing ARDS when their underlying illness is comparatively less severe. Similarly to ambient pollution, cigarette smoke exposure likely predisposes the lung to injury in the setting of a second insult such as trauma, multiple transfusions, or sepsis . This concept was elegantly demonstrated in an experimental model in healthy humans who were exposed to inhaled lipopolysaccharide .BAL and plasma biomarkers for alveolar epithelialcapillary permeability, inflammation, and alveolar endothelial dysfunction were compared between self-reported smokers and nonsmokers. Absolute measurements were consistent with more alveolar permeability to protein and inflammation in smokers, and statistical tests of interaction demonstrated that smoking potentiated these responses to LPS.In mice, cigarette smoke exposure itself does not cause frank lung injury, but mice exposed to cigarette smoke develop worse pulmonary edema, increased vascular permeability, worse histologic injury, and increased biomarker evidence of inflammation after exposure to LPS.

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Counts and rates were not reported when n < 16 to protect the identity of individuals in the dataset

Specific to being a sexual minority, GBM who were not out about their gay identity were less likely to report having any other mental health condition at the univariable level than those who were open about being gay. We posit that this may be due to the fact that individuals who are public regarding their sexual orientation are easier targets for harassment or discrimination. This is supported by findings from D’Augelli and Grossman , where GBM who came out at an earlier age and GBM who spent more years out of the closet were more likely to experience victimization than individuals who came out later or who spent less time out of the closet. More generally speaking, Meyer argues that experiences of victimization in the forms of stigma, prejudice, and discrimination that GBM experience may be the cause for the higher prevalence of mental health conditions in GBM populations and refers to this as minority stress . Stigma may also help explain why HIV-positive GBM were more likely to report a substance use disorder in our study. HIV-related stigma has been linked to poorer mental health in a meta-analysis by Logie and Gadalla and a review by Smit and colleagues . Readers should be cautious when interpreting our results. Most notably our results rely on participants’ retrospective self-report of recent substance use and sexual behavior and compare these data with lifetime mental health diagnoses. As such, we are limited in determining causal direction, but instead position these findings as a more representative profile of GBM who had ever been diagnosed with a mental health condition given our use of respondent-driven sampling. We did not conduct diagnostic interviews to account for undiagnosed conditions,mobile racking for growing and thus underestimated the true burden of mental health issues. We attempted to address current symptomology through the inclusion of AUDIT and HADS scores.

However, given the paucity of validation studies for AUDIT, but particularly HADS within GBM populations, we caution the interpretation of these findings and call for new research validation studies with GBM populations. Regardless, our analyses demonstrate some measure of construct validity in that higher scores on both measures were linked to reporting mental health conditions in our study. Our measure of sexual orientation “outness” was only asked for gay-identified participants, and a general measure should be included in future studies. A nurse-administered structured interview was used to assess mental health diagnoses and current treatments to ensure these questions were more accurately understood and answered. Given the potential impact of social desirability and reporting bias , we used CASI to collect data regarding illicit substance use. However, we did not use drug testing to confirm or correct self-report data and likely underestimated the true prevalence of substances used . Despite these shortcomings, one of the strengths of our study is the use of RDS to overcome previous sampling shortfalls with GBM and produce a more accurate representation of the population parameters of these variables of interest for the GBM population of Metro Vancouver. Our study also adds new data regarding the detailed prevalence of substance use and mental health conditions among GBM populations in Canada filling a gap in currently available published literature. Finally, our work goes further to examine explicitly the relationship between substance use and mental health conditions among GBM identifying important relationships that have implications for counseling and public health services, interventions, and policy. The greater burden of mental health conditions and higher prevalence of substance use in GBM populations highlight the need for a more explicit focus on these issues in research and service provision. Mental health specialists should be aware of the relationships with sexuality and substance use when working with GBM clients, particularly issues regarding identity disclosure, number of sexual partners, and higher background community prevalence of substance use .

Future research should seek to validate current measures and to confirm the relationship between substance use and mental health conditions, which has been demonstrated to produce a syndemic including suicidal ideation among GBM and HIV acquisition . Our study was based in a major metropolitan area, which may limit generalizability to GBM in rural or remote regions, whom are a population with distinct needs and challenges that should be further examined. In order to evaluate generalizability, additional research is needed to explore these issues among GBM populations in other urban and non-urban centers across Canada, particularly if these studies employ RDS or other more representative sampling methods. Given the role of social factors in mental well-being, future research should directly examine experiences of homophobia or heterosexism as possible precursors to substance use and/or mental health issues, along with potential mediators and protective factors. Examining demographic factors independent of one another may not reflect the diversity of experiences that exists among GBM. Using an intersectional approach, which looks at how multiple identities such as race, sexual orientation, and class, interact with one another to shape experiences , may also explain the distribution and experiences of mental health and substance use within diverse communities of GBM. In spite of experiences of marginalization and discrimination, many GBM do not go on to develop mental health conditions or engage in harmful substance use. Shilo, Antebi, and Mor found that factors such as support of family and friends, meaningful connections with the LGBT community, and having a steady partner, protect against developing poorer mental health in lesbian, gay, bisexual, queer, and questioning adults. Thus, more focus on factors such as these that promote resiliency in GBM would be beneficial to include in future research on mental health and substance use in these populations. Compared with the Canadian population, GBM living in Metro Vancouver have increased levels of substance use and mental health conditions. The strong link between substance use and mental health among GBM has important implications for public health promotion programming and care service provision.

A number of social determinants increase the likelihood of mental health diagnosis among GBM, including disclosure of sexuality, low income, and race/ethnicity. GBM living with HIV were significantly more likely to have a lifetime doctor-substance use disorder compared with HIVnegative GBM. Greater attention to these issues is needed across all health and social services given their disproportionate effect on GBM populations. Health promotion and interventions should address issues of substance use, mental health, and sexuality in unison and future research can help direct these efforts by examining possible precursors of these issues, which may be the result of discrimination, prejudice, and stigma.Tobacco use in the general population has declined substantially in the past three decades, but rates remain high in certain populations. The prevalence of tobacco use in the homeless population is 3 to 4 times that of the general population.Among homeless adults, tobacco-related chronic diseases including heart disease, cancer and chronic obstructive pulmonary disease are common and contribute significantly to the increased morbidity and mortality in this population.Among a clinic-based sample of homeless adults aged 50 and older, tobacco-attributable deaths accounted for 26% of the overall mortality and 54% of substance-related mortality.The health consequences of smoking occur disproportionately among older individuals because of the cumulative effects of long term smoking.Among older adults,modular cannabis grow racks tobacco-related chronic diseases, particularly chronic obstructive pulmonary disease and coronary heart disease, are among the most common reasons for emergency health care services and preventable hospitalizations.Current tobacco use contributes significantly to all-cause mortality among older adults, suggesting that tobacco cessation at any age is likely to significantly reduce tobacco-related morbidity and mortality.In a nationally representative sample, older adults were less likely to quit smoking than younger adults because of reduced interest in quitting smoking, higher nicotine dependence, and lower support for smoke-free norms.This highlights the need for tobacco cessation interventions that address tobacco-related beliefs and practices among older adults. Over the past 2 decades, the median age of homeless adults increased from 37 years in 1990 to almost 50 years in 2010.Despite increased tobacco-related morbidity and mortality among older homeless adults, little is known about tobacco use and cessation behaviors in this population. Prior research on tobacco use in the homeless population has focused on younger adults, where the average age of study participants in previous studies was less than 44 years.The high prevalence of tobacco use and the increased burden of tobacco-related chronic diseases with aging underscore a need for studies that characterize tobacco use and cessation behaviors among older homeless adults in order to develop tobacco control interventions that address the unique needs of this population. We conducted a study of a cohort of homeless individuals aged 50 and older sampled from the community to examine rates of and factors associated with tobacco cessation.

We hypothesized a priori that current smoking would be associated with symptoms of depression, substance use disorders, history of incarceration, and history of staying in shelters.We also hypothesized that persons who reported smoking heavily or having symptoms of depression at enrollment would be less likely to make a quit attempt at follow-up.We used previously validated questions on tobacco use at the enrollment and 6-month follow-up interviews. We asked participants whether they had ever smoked 100 cigarettes in their lifetime, and classified those who did as ever-smokers. We classified ever-smokers who reported smoking “every day or some days” as current smokers, and those who reported “not smoking at all” as former smokers. We asked current daily smokers to report the number of cigarettes smoked daily. For current non-daily smokers, we estimated average daily cigarette consumption based on self-reported numbers of cigarettes smoked on smoking days in the past 30 days. Participants reported how soon they had smoked their first cigarette after waking, which we dichotomized as greater or less than 30 minutes. We asked current smokers about their intentions to quit smoking . We asked current smokers to report whether they had stopped smoking for 1 day or longer in the past 6 months because they were trying to quit smoking. We asked participants who responded affirmatively to making a quit attempt to report the length of their last quit attempt. We defined reporting a quit attempt in the past 6-months at the follow-up visit as the primary outcome variable. We determined the proportion of participants who were abstinent for 30 days and 90 days at the 6-month study visit using self-reported information on the length of the last quit attempt. At the 6-month follow-up visit, we obtained additional information from participants on their quitting behaviors.If participants reported having made a quit attempt during the past 6 months, we asked them to report the medications, strategies, and support system they had used during their last quit attempt. Participants reported whether they had used nicotine replacement therapy and/ or any of the US Food and Drug Administration -approved medications for smoking cessation during their last quit attempt. Participants reported whether they had used other strategies to quit smoking including gradually cutting back on cigarettes, switching to smokeless tobacco, other combustible tobacco , or electronic cigarettes, or giving up cigarettes all at once. Participants self-reported their use of a telephone quit line, group or one-on-one smoking cessation counseling, hypnosis or acupuncture, and other internet or family-based support for smoking cessation. Participants also reported whether they had received advice to quit cigarette smoking from their health care provider in the past 6 months, and whether they had acted on the advice to quit smoking.Participants self-reported age, gender and race/ethnicity at the enrollment visit. At the enrollment and follow-up interviews, participants reported whether they had spent any time in jail or prison in the past 6 months. At both visits, we gathered residential history of every place that the individual had stayed, by using a 6-month follow-back residential calendar.We categorized participants as having stayed in shelters if they reported staying in a homeless shelter for single adults or families during the past 6 months.We used questions derived from the World Health Organization’s Alcohol, Smoking, and Substance Involvement Screening Test  to assess use of cannabis, cocaine, amphetamines, and opioids. We dichotomized the severity of substance use as low versus moderate to high risk .We administered the WHO’s Alcohol Use Disorders Identification Test with a shortened time frame of the previous 6 months to assess risk and severity of alcohol use disorders. We categorized AUDIT scores of 8 or more as indicative of hazardous and harmful alcohol use or an alcohol disorder.

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Edaravone is an antioxidant and ROS scavenger marketed as a neurovascular protective agent

While the consensus on a healthy diet has generally been interpreted to mean limiting intake of sodium, red meat and saturated fat intake, several other dietary factors have been reported to reduce stroke risk, such as diets rich in magnesium, flavonoids, lycopenes, fruits and vegetables, and chocolate. Further, the Mediterranean diet was found to reduce cardiovascular risk in a randomized trial.Intensive exercise has been also reported to have a benefit in secondary stroke prevention.Thus, it is incumbent upon healthcare providers to emphasize lifestyle changes for stroke risk reduction. Pharmacological approaches to reduce stroke risk often include agents which prevent or reduce thrombus formation. Anti-platelet agents are used for secondary prevention in most non-cardiogenic IS patients to prevent worsening of atherosclerotic disease. The main mechanism of IS reduction are through blockade of platelet aggregation and activation through the suppression of thromboxane A2 via cyclooxygenase-1 blockade and upregulation of cAMP via phosphodiesterase 3 or P2Y12 receptor blockade. Aspirin, clopidgrel, dipyridamole, and cilostazol have all demonstrated efficacy for secondary prevention of IS through this anti-platelet effect. Prasugrel is newer antiplatelet agent, but has not been shown to be superior to conventional anti-platelet agents in recent study.Ticagrelor, a recently approved anti-platelet inhibitor of the P2Y12 ADP receptor in coronary disease, was shown to also have efficacy in primary and secondary IS prevention.Dual antiplatelet treatment typically consists of aspirin plus clopidogrel has met with conflicting results. Early studies suggested that such combination therapy led to unacceptably high risks of major cerebral and gastrointestinal bleeding and a recent metaanalysis indicated that such hemorrhage due to DAPT negated any antithrombotic benefit. It should be pointed out that these early studies used long term DAPT for months or even years. More recent studies of short term DAPT have now shown that this approach can further reduce stroke risk while not increasing the risk of significant hemorrhage .As such,grow racks indoor it is now common practice to prescribe DAPT for periods of 21 or 90 days after non-cardiogenic IS.

It should also be noted that DAPT may increase HTf when used with t-PA in experimental stroke models,In contrast, a recent study showed that combination therapy of aspirin or clopidogrel with cilostazol has been reported not to increase the incidence of HTf and to reduce relative risk of recurrent IS by 51% compared to single anti-platelet therapy.Cilostazol is also thought to have pleiotropic effects such as an improvement of endothelial function by inhibition of smooth muscle cell proliferation and reduction of inflammation.In a recent experimental study, cilostazol was also shown to have a neuroprotective effect via reduction of inflammatory molecules, stabilization of the blood-brain barrier, and prevented apoptosis.Significant extracranial carotid artery stenosis is detected about 15% of IS patients. Revascularization, either via endarterectomy or endovascular approaches, of symptomatic stenotic carotids has been shown to significantly reduce stroke risk, especially if carried out within two weeks of the index transient ischemic attack or stroke.While endarterectomy has long been the mainstay of revascularizing stenotic carotids, endovascular approaches include carotid artery angioplasty followed by stenting , which has the advantage of being less invasive and similarly efficacious.Less clear is the role of carotid revascularization on asymptomatic carotids.In patients with a cardiogenic cause of stroke, anti-thrombotic therapy to prevent thrombus formation has been shown in several studies to substantially reduce recurrent stroke, particularly for atrial fibrillation.The vitamin K antagonist warfarin has been the most widely studied and used, but recently, orally available direct thrombin and factor X inhibitors have been shown to be as effective and easier to manage than warfarin. Several clinical studies have shown that DOACs are noninferior to warfarin in the prevention of IS with a lower incidence of significant HTf. Further, the presence of cerebral microbleeds , which may be an indication of underlying cerebral amyloid angiopathy, increases the risk for cerebral hemorrhage in association with anti-thrombotic therapy. The incidence of intracranial hemorrhage in the presence of CMBs during DOAC treatment has been reported to be less than anti-platelet and warfarin therapy. This is thought to be due to the ability of DOACs to avoid inhibiting factor VII, although hemorrhage risk is still higher compared to that amongst patients without CMBs.

Thus, it is still not recommended to initiate DOAC or other anticoagulant treatment in this patient population.ESUS are now increasingly thought to be due to occult atrial fibrillation , in part, due to the availability of long term cardiac monitoring technology ; however, it is unclear whether these patients should be empirically anticoagulated.DOACs were considered for secondary prevention of ESUS; however, a few studies have failed to show that this approach is effective.Other embolic sources such as aortic plaque, patent foramen ovale, and neoplasm have been identified as the etiology of ESUS where anticoagulation is not always the indicated treatment. Hence, documentation of occult AF will be important prior to initiating anticoagulant therapy. Other beneficial effects of DOACs have been suggested in experimental studies. Dabigatran, a direct thrombin inhibitor, has been shown to inhibit microglial and astrocyte activation.Edoxaban, a factor X inhibitor, has also been shown to have anti-inflammatory effects via suppression of PAI-1, MCP-1, and TNF-α. Some ‘natural’ approaches have been studied in stroke prevention as well, but have not been routinely implemented at the clinical level. Polyphenol supplementation has been proposed as a preventive agent for IS. In a previous study, polyphenol intake was thought to act as an antioxidant, leading to reduction in atherosclerosis.It is also thought to have other beneficial properties such as regulating neurotrophin levels, especially nerve growth factor and brain-derived neurotrophic factor . Epigallocatechin gallate , which is a polyphenol found in green tea, has gained interest for its putative antioxidant and neuroprotective effects via prevention of NF-κB activation, inhibition on PI3K/Akt signaling, and improvement of mitochondrial dysfunction.EGCG also seems to the downregulate MMP-2 and MMP-9 and upregulate the endogenous t-PA inhibitor plasminogen activator inhibitor-1 . These latter observations suggest that EGCG may have a role as an adjunctive agent to t-PA by extending the therapeutic time-window for thrombolytic treatment while reducing other undesirable side effects of t-PA treatment such as severe HTf, brain edema and BBB disruption. Other polyphenols have demonstrated antioxidant effects, which have the potential to reduce stroke risk. Resveratol, a component of red wine, has been shown to inhibit phosphodiesterase and regulate cAMP, AMPK, and SIRT1 pathways during ischemic injury. Salvianolic acid has been shown to have neuroprotective effects dependent on mitochondrial connexin43 via PI3K/Akt pathway.

Flavonol rich diets has been reported for a 14% relative risk reduction of IS. Flavonoids is main sources of apple polyphenol, which has been reported to reverse oxidative stress via P38 mitogen-activated protein kinase signaling pathway.harmacological recanalization with t-PA has been the mainstay for acute IS treatment for several decades. t-PA therapy has been shown to improve neurological outcome provided it is initiated within 4.5 h from symptom onset. In addition to rt-PA therapy, recent randomized controlled trials have demonstrated the efficacy of mechanical thrombectomy in large vessel stroke.98) In several of these trials, pre-treatment with t-PA before MT intervention was superior to t-PA alone. A few studies also showed that MT could be extended to even 24h after stroke onset, provided imaging studies showed a large mismatch. The DAWN ,DEFUSE3 , and EXTEND studies all evaluated endovascular methods of thrombectomy to acutely revascularize occluded large cerebral vessels that cause stroke. These studies have not only shown that acute revascularization can improve stroke outcome from longer time windows,grow shelf rack but can also lengthen the therapeutic time windows for t-PA. These studies utilized imaging based criteria to identify appropriate candidates. In particular, those studies which showed longer time windows for thrombectomy used imaging to demonstrate a large, and thus salvageable ischemic penumbra in relation to the ischemic core . Further, imaging criteria have allowed for the use of t-PA therapy in so-called “wake-up stroke”, where the time of stroke onset is unclear because the patient reports waking up with a neurological deficit after being neurologically intact at the time of sleep. Such cases may be pre-selected by mismatch from diffusion weighted and FLAIR MRI.While the expansion of therapeutic time windows and improved outcomes have been shown in acute revascularization approaches, reperfusion injury has the potential to worsen outcome, compared to no revascularization. While this phenomenon is well established in experimental stroke models, its existence in clinical stroke has been debated. Nevertheless, some have reported a hyperintense acute reperfusion marker on MRI which is thought to predict HTf and clinical worsening in some IS patients, and this has been suggested R/I in humans.In experimental studies, R/I has been attributed to the introduction and generation of ROS when a previously occluded vessel is opened. This flood of ROS leads to inflammation. Inflammation then results in the generation of various damaging immune mediators, effector molecules and more ROS. ROS can also lead to apoptosis/necrosis via DNA/RNA damage, lipid peroxidation, and the reduction of ATP production. Further, t-PA treatment can promote extracellular matrix damage to lead to HTf. Hence, targeted R/I treatments in conjunction with t-PA and/or MT has the potential to further improve neurological outcomes.A few potential adjunctive agents have been explored at the clinical level.At the clinical level, edaravone contributes to improving neurological function and reducing adverse events. In the PROTECT 4.5 trial, the efficacy and safety of combination therapy with edaravone and t-PA in stroke patients suggested that combination therapy might increase the numbers of patients with better outcomes, accelerated recanalization and reduced HTf.

The YAMATO study showed that the timing of edaravone infusion did not affect the rate of early recanalization, symptomatic HTf, or favorable outcomes after t-PA therapy. However, early edaravone infusion in parallel with endovascular revascularization led to better functional outcomes at discharge, lower mortality, and lower incidence of HTf in a recent clinical trial. Edaravone has been already approved for the treatment of IS patients who present within 24 h of the onset of symptoms in Japan and other countries, but not the United States. Thus, the prospects of adding edaravone to t-PA and MT seem favorable. Therapeutic hypothermia has already been shown to improve neurological outcomes in comatose survivors of cardiac arrest and neonatal hypoxic encephalopathy. While it has yet to be shown whether it has any role in patients with IS, major mechanisms for its neuroprotective effect seems to be related to its effects on multiple cell death pathways including inflammation, apoptosis, excitotoxicity and preservation of metabolic stores.HT has also been shown to reduce BBB disruption and HTf in relation to t-PA use in experimental models.Combination therapy with HT and t-PA also reduced HTf and endogeneous tPA expression, and has the potential to extend the time window for other acute therapies. Few clinical studies have been carried out in IS. The ReCCLAIM and ICTuS studies assessed the combination therapy with rt-PA and HT in IS patients with large pretreatment infarcts, and both trials showed that this approach was safe and may even reduce reperfusion injury, as outcomes were improved compared to stroke patients who did not receive HT. The ICTuS2 study showed the safety and feasibility of both HT and HT with t-PA, although cooling increased the incidence of pneumonia. HT has been also combined with MT with selective brain cooling elicited by intra-arterial chilled saline infusion and was shown to be both safe and feasible.The RECCLAIM-Ⅱ also examined MT with HT; however, this trial was stopped early for lack of funding.A recent laboratory study also showed that the neuroprotective effect of HT differentially affects cells of neurovascular unit depending on the depth, duration and even timing of cooling.Yet, clinical studies used a single target temperature with fixed duration . Thus, it may be important to design future clinical trials with adjusted temperature and cooling duration depending on targeted cell type for neuroprotection versus vasculoprotection. Recent years have seen an advent in population-based studies that examine the prevalence, etiology, and developmental trajectories of diverse sub-clinical psychopathological symptoms that pose a risk for the later development of severe mental illnesses. It is increasingly recognized that most categorically defined psychiatric disorders occur on a spectrum or continuum that is not necessarily normally distributed , show high heterogeneity and symptom overlap, and share genetic and environmental risk factors . Therefore, population-based studies of psychopathology in youth assess a broad spectrum of symptoms as well as genetic risk, cognitive and general functioning, socioeconomic, and environmental factors to yield a more complete understanding of symptom etiology and development.

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What Can You Grow With Vertical Farming

Frequent testing for HIV infection can identify new infections early, and it is essential in ending the HIV epidemic. HIV self-testing is an alternative HIV screening method that is commercially available, approved by the Food and Drug Administration, and can reach individuals who have never tested before. It can reach populations at risk, such as Black and Latinx individuals, identify new cases of HIV infection, and lead individuals to seek additional HIV prevention options, such as testing for sexually transmitted infections or pre-exposure prophylaxis. Prevention studies and public health programs have been adopting HIV self-tests and combining them with new technologies, such as smartphone apps or smart devices, to reach populations with high incidence of HIV infection, such as Black and Latinx MSM. Despite multiple efforts, the uptake of HIV testing remains inadequate, especially among individuals at high risk for HIV infection. Thus, optimizing the promotion of HIV testing is important. Due to their extensive popularity, social media sites and dating apps have been used to promote and recruit participants for HIV prevention research studies with high rates of success. According to a recent Centers for Disease Control and Prevention report reviewing HIV self-testing programs, 27 health departments and community organizations used multiple platforms for promotion, mainly social media followed by “traditional” printed media and dating apps . Compared to in-person recruitment, web-based platforms have the capacity to reach a high number of difficult-to-reach populations and individuals at risk , overcoming stigma or other logistic obstacles in a cost-efficient manner. Indeed, the New York Department of Public Health used advertisements on social media, dating apps,plant grow rack and websites to reach 28,921 users, identifying 17,383 eligible MSM, transgender, and gender nonconforming individuals during its HIV self-testing campaign. Most of the participants were under the age of 35 years and identified as Black or Latinx. In addition, the first wave of this campaign reached 3359 users in only 23 days, distributing 2497 home test kit voucher codes to eligible users.

Social media and dating apps have been widely adopted as means of promoting HIV home testing. Although different from dating apps and social media sites, information search sites are commonly used for seeking information on HIV testing and PrEP and could represent a promising outreach avenue. Their use for enrollment and HIV testing promotion has not been evaluated. However, little is known about the relative effectiveness of these different web-based platforms in promoting HIV self-testing. Parker et al conducted a secondary analysis in a study enrolling substance-using sexual and gender minority adolescents and young adults to evaluate the efficacy of their enrollment strategy. The study used multiple methods to enroll participants, including social media platforms , dating apps , internet-based health boards, and venue-based enrollment. They recorded 17,328 visits to the eligibility screener on the landing page, with a 36.2% screener survey completion ratio. Researchers identified 580 participants among those who consented and were eligible to participate , indicating a high recruitment proportion. The majority of their participants were enrolled from Facebook, Instagram, and Grindr. Studies and programs use these platforms based on the experience of previous studies and expert recommendations. Data on the effectiveness of public health promotion through different platforms leading to testing or PrEP are missing. We can only infer the effectiveness of promotion indirectly, as head-to-head comparisons of the effectiveness of the different platforms and sites to reach individuals for public health promotion are missing. This would allow researchers and prevention programs to optimize their budget and strategy. The primary objective of this study was to compare ordering of HIV self-testing kits among users recruited through 3 different types of web-based platforms, including social media, dating apps, and information search sites. Test kit ordering was used as a proxy for analyzing the effectiveness of promoting HIV self-testing on different sites. The secondary goal was to evaluate the association of key moderating variables—substance use, psychological readiness to test, and perceptions and attitudes related to HIV testing—with the ordering of HIV self-testing kits.

In this longitudinal observational cohort study, advertisements promoting free HIV self-testing were placed on three platform types: social media , dating apps , and information search sites . The advertisements were organized in 2 “waves,” with each wave consisting of 1 social media website, 1 dating app, and 1 information search site. The Wave 1 recruitment stopped early, as Grindr unexpectedly stopped running all self-service platform advertisements due to a change in corporate ownership. We continued with Wave 2 as planned and a relaunched Wave 1 once Grindr access was restored. Before launching each wave, we allocated the same amount of funds for each of the 3 sites and optimized them to run for at least 30 calendar days by dividing the available funds in the prespecified promotional period. However, due to slow enrollment during the COVID-19 pandemic, we extended the second phase of Wave 1 up to 63 days. The advertisement used on social media and dating apps was an image that included a person and text , whereas promotional keywords related to HIV testing and PrEP were selected for information search sites . The same image and keywords were used in all waves. The advertisements were launched in the District of Columbia and 8 states , which were selected based on their high incidence of HIV infection. More information regarding the promotional campaign can be found in the published protocol. Upon clicking on the study advertisement, website users landed on the study information page, where they received general information about the study, underwent eligibility screening, and reviewed study procedures. Following electronic informed consent, participants completed the baseline assessment and were emailed a unique electronic code to order their HIV home self-test kit through Orasure.com . Participants also received an electronic coupon for a free telemedicine PrEP visit. Participants were followed up at 14 and 60 days after enrollment. At follow-up, participants were asked about their HIV self-test use and self-test results; depending on their self-test result, they were asked if they visited a PrEP provider and started PrEP, as well as their opinions on PrEP. If they tested positive for HIV antibodies with the home self-test kit, they were asked if they had visited a clinic for confirmatory testing and HIV treatment. In addition, we tracked test kit orders through automated reports, collected anonymous advertisement metrics through the web applications of the platforms, and recorded the costs for each promotion site and wave.

Participants who were enrolled from Google and Facebook while Grindr was inactive were excluded from analyses. This ensured that we included data when all 3 sites were active and thus had an equal chance to enroll participants. Participants who did not order a test kit within 60 days of the test code being emailed to them were classified as “not ordered a self-test kit.” The 2 advertisement periods of Wave 1 were combined before analysis. Prior to statistical modeling, the number of HIV home self-test kits ordered from each platform, specific platform types , and number days of recruitment in each wave were summarized. In addition, the observed daily self-test kit order rates for each site and platform type were calculated . Per our primary research question, we intended to determine the statistical difference in the self-test kit ordering rates by platform type using a Poisson regression model; however, due to significant platform-by-wave interactions and widely differing order rates between sites within the same platform, it was not appropriate to combine or pool sites across the same platform for statistical evaluation of the platform difference. Therefore, we compared the specific platform differences in terms of the order rates within the same wave. We conducted pairwise comparison for all 6 sites from the 2 waves with multiple testing adjustments using the Hochberg method. Demographic and baseline characteristics were presented using summary statistics. Continuous variables were summarized using percentiles , and means with their SDs. Categorical variables were summarized with frequencies and percentages. To assess differences in the measures between participants who ordered a test kit and those who did not order a test kit, we used the Student t test for continuous variables, Fisher exact test for categorical variables,sliding grow racks and Wilcoxon rank sum test for Likert responses. Data analysis was carried out using Statistical Analysis Software . In this study of MSM at risk for HIV infection, we investigated the effectiveness of promoting free home HIV self-test kits on various internet platforms. More than half of the participants ordered a self-test kit, although only a small proportion of HIV-negative individuals reported seeking PrEP services. Our results showed that dating apps were the most efficient platform to distribute HIV self-test kits to men at high risk for HIV infection. Risk behavior, attitudes toward HIV testing and treatment, perception of HIV-related stigma, and medical mistrust were not associated with ordering a self-test kit. Finally, we recorded high prevalence of alcohol and cannabis use among participants. Overall, information search sites performed poorly in recruiting and enrolling individuals. The site advertisement metrics showed a better click-through rate than social media and a similar number of users screened, but ultimately only a small number of individuals enrolled in the study. Search engines have a broad audience as they are available to everyone with access to the internet, and they do not require an account. In comparison, dating apps had the highest click-through rate, screening numbers, and enrollment. Users of dating apps are more likely to be MSM and engage in high-risk behaviors, which could explain the higher engagement with the promoted study advertisements. Consequently, dating apps may be more cost-efficient in enrolling select individuals compared to other platforms. Using search engines for promotion may reach higher numbers of individuals, but dating apps achieved higher interaction with the promotion message in this study. Another important difference between platforms that may have affected individual site performance is the type of advertisement message.

Social media and dating apps use blast advertisements with images and text, whereas search engines use text-only promotional content. Researchers attempting to identify the best type of advertisement to reach MSM through the internet for free at-home HIV testing showed that the click-through rate for a text-only advertisement on Google was 0.38%, whereas that for advertisements with images, such as the ones used in social media and dating apps, was higher, between 0.77% and 2%. There is a lack of published data regarding the performance of promotional campaigns to enroll participants or promote HIV prevention messages. This limits our capacity to make comparisons with similar campaigns. Our data showed that the cost of enrolling individuals from dating apps is lower compared to that for social media and information search sites. This is mainly due to the higher engagement and higher number of participants enrolled through dating apps. Future studies should collect and report advertisement campaign metrics as well as the costs of enrollment per participant screened and enrolled, which can allow for a better evaluation of the cost-effectiveness of different platforms.Our study demonstrated that HIV self-testing can reach individuals at high risk. We enrolled Latino and Black MSM at a high risk for HIV infection in 10 areas with a high incidence of HIV infection. The study population included individuals with inconsistent and infrequent condom use, and nearly 25% of them reported that they had never tested for HIV. We also identified individuals who reported a preliminary positive result, which demonstrates the capacity of HIV home testing to reach hard-to-reach populations, overcome obstacles, and increase testing. Our findings underline the importance of identifying the best possible promotional platform that will allow public health programs to reach an even larger number of individuals at risk. Our findings did not identify any major differences between participants who ordered a kit compared to those who did not order a test kit. However, our data showed a small statistical difference in terms of the questionnaires on self-perceived stigma, as well as the participant perceptions about the risks of HIV infection. Public health stakeholders should continue their efforts to educate individuals about HIV and support vulnerable individuals against stigma. Substance use was common among study participants, especially alcohol and cannabis use. Similarly, Westmoreland et al also reported a high incidence of cannabis use and alcohol use among a sample of MSM, transgender men, and transgender women. Heavy alcohol use is associated with an increase in sexual behaviors that might put persons at risk for HIV acquisition and transmission.

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