Genome editing in the mouse brain with minimally immunogenic Cas9 RNPs.

Transient delivery of CRISPR-Cas9 ribonucleoproteins (RNPs) into the central nervous system (CNS) for therapeutic genome editing could avoid limitations of viral vector-based delivery including cargo capacity, immunogenicity, and cost. Here, we tested the ability of cell-penetrant Cas9 RNPs to edit the mouse striatum when introduced using a convection-enhanced delivery system. These transient Cas9 RNPs showed comparable editing of neurons and reduced adaptive immune responses relative to one formulation of Cas9 delivered using AAV serotype 9. The production of ultra-low endotoxin Cas9 protein manufactured at scale further improved innate immunity. We conclude that injection-based delivery of minimally immunogenic CRISPR genome editing RNPs into the CNS provides a valuable alternative to virus-mediated genome editing.

Cumulative housing cost burden exposures and disadvantages to children's well-being and health.

Housing affordability is a growing challenge for households in the United States and other developed countries. Prolonged exposure to housing cost burden can have damaging effects on households, and, in particular, children. These burdens can exacerbate parental stress, reduce investments in children and expose households to greater neighborhood disadvantage. In this study, we use national survey data to assess whether cumulative housing cost burden exposure is associated with disadvantages to children's well-being and health. We observe that long-term exposures are linked to lower achievement in math and reading standardized test scores, as well as higher levels of behavior problems. Moreover, we identify that three mechanisms--caregiver distress, economic strain, and neighborhood disadvantage--operate as mediating pathways for these disadvantages to different degrees between these three outcomes. Overall, our study highlights how the dimension of time is increasingly important to our understanding of the challenges that families face related to housing affordability.

Elucidation of physico-chemical principles of high-density lipoprotein-small RNA binding interactions.

Extracellular small RNAs (sRNAs) are abundant in many biofluids, but little is known about their mechanisms of transport and stability in RNase-rich environments. We previously reported that high-density lipoproteins (HDLs) in mice were enriched with multiple classes of sRNAs derived from the endogenous transcriptome, but also from exogenous organisms. Here, we show that human HDL transports tRNA-derived sRNAs (tDRs) from host and nonhost species, the profiles of which were found to be altered in human atherosclerosis. We hypothesized that HDL binds to tDRs through apolipoprotein A-I (apoA-I) and that these interactions are conferred by RNA-specific features. We tested this using microscale thermophoresis and electrophoretic mobility shift assays and found that HDL binds to tDRs and other single-stranded sRNAs with strong affinity but did not bind to double-stranded RNA or DNA. Furthermore, we show that natural and synthetic RNA modifications influenced tDR binding to HDL. We demonstrate that reconstituted HDL bound to tDRs only in the presence of apoA-I, and purified apoA-I alone were able to bind sRNA. Conversely, phosphatidylcholine vesicles did not bind tDRs. In summary, we conclude that HDL binds to single-stranded sRNAs likely through nonionic interactions with apoA-I. These results highlight binding properties that likely enable extracellular RNA communication and provide a foundation for future studies to manipulate HDL-sRNA interactions for therapeutic approaches to prevent or treat disease.

Using Latent Profile Analysis to Identify Associations Between Gestational Chemical Mixtures and Child Neurodevelopment.

BACKGROUND: Unsupervised machine learning techniques have become increasingly popular for studying associations between gestational exposure mixtures and human health. Latent profile analysis is one method that has not been fully explored. METHODS: We estimated associations between gestational chemical mixtures and child neurodevelopment using latent profile analysis. Using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) research platform, a longitudinal cohort of pregnant Canadian women and their children, we generated latent profiles from 27 gestational exposure biomarkers. We then examined the associations between these profiles and child Verbal IQ, Performance IQ, and Full-Scale IQ, measured with the Wechsler Preschool and Primary Scale of Intelligence, Third Edition (WPPSI-III). We validated our findings using k-means clustering. RESULTS: Latent profile analysis detected five latent profiles of exposure: a reference profile containing 61% of the study participants, a high monoethyl phthalate (MEP) profile with moderately low persistent organic pollutants (POPs) containing 26%, a high POP profile containing 6%, a low POP profile containing 4%, and a smoking chemicals profile containing 3%. We observed negative associations between both the smoking chemicals and high MEP profiles and all IQ scores and between the high POP profile and Full-Scale and Verbal IQ scores. We also found a positive association between the low POP profile and Full-Scale and Performance IQ scores. All associations had wide 95% confidence intervals. CONCLUSIONS: Latent profile analysis is a promising technique for identifying patterns of chemical exposure and is worthy of further study for its use in examining complicated exposure mixtures.

Who benefits most from a prenatal HEPA filter air cleaner intervention on childhood cognitive development? The UGAAR randomized controlled trial.

BACKGROUND: Air pollution exposure during pregnancy affects children's brain function. Maternal stress and nutrition, socioeconomic status, and the child's sex may modify this relationship. OBJECTIVE: To identify characteristics of children with the largest increases in full-scale IQ (FSIQ) after their mothers used HEPA filter air cleaners during pregnancy. METHODS: In this randomized controlled trial we randomly assigned women to receive 1-2 air cleaners or no air cleaners during pregnancy. We analyzed maternal hair samples for cortisol and dehydroepiandrosterone (DHEA). When the children were 48 months old, we measured FSIQ with the Wechsler Preschool and Primary Scale of Intelligence. We evaluated ten potential modifiers of the intervention-FSIQ relationship using interaction terms in separate regression models. To account for correlations between modifiers, we also used a single regression model containing main effects and intervention x modifier terms for all potential modifiers. RESULTS: Among 242 mother-child dyads with complete data, the intervention was associated with a 2.3-point increase (95% CI: -1.5, 6.0 points) in mean FSIQ. The intervention improved mean FSIQ among children of mothers in the bottom (5.4 points; 95% CI: -0.8, 11.5) and top (6.1 points; 95% CI: 0.5, 11.8) cortisol tertiles, but not among those whose mothers were in the middle tertile. The largest between-group difference in the intervention's effect was a 7.5-point (95% CI: -0.7, 15.7) larger increase in mean FSIQ among children whose mothers did not take vitamins than among children whose mothers did take vitamins (interaction p-value = 0.07). We also observed larger benefits among children whose mothers did not complete university, and those with lower hair DHEA concentrations, hair cortisol concentrations outside the middle tertile, or more perceived stress. CONCLUSION: The benefits of reducing air pollution during pregnancy on brain development may be greatest for children whose mothers who do not take vitamins, experience more stress, or have less education.

An updated systematic review and meta-analysis on portable air cleaners and blood pressure: Recommendations for users and manufacturers.

Fine particulate matter (PM2.5) air pollution is a leading contributor to the global burden of cardiovascular disease (CVD). One important underlying mechanism is an increase in blood pressure (BP). A growing number of studies have reported a beneficial effect of portable air cleaners (PACs) on systolic and diastolic BP; SBP and DBP. We conducted an updated systematic review and meta-analysis of studies using true versus sham mode filtration reporting the effects on BP. Of 214 articles identified up to February 5, 2023, seventeen (from China, USA, Canada, South Korea and Denmark) enrolling approximately 880 participants (484 female) met the inclusion criteria for meta-analyses. Aside from studies conducted in China, research on PACs and BP has been conducted in relatively low pollution settings. Mean indoor PM2.5 concentrations during the active and sham mode purification were 15.9 and 41.2 µg/m3, respectively. The mean efficiency of PACs against indoor PM2.5 was 59.8 % (ranging from 23 % to 82 %). True mode filtration was associated with a pooled mean difference of - 2.35 mmHg (95 % confidence interval [CI]: - 4.5, - 0.2) and - 0.81 mmHg (95 % CI: - 1.86, 0.24) in SBP and DBP, respectively. After removing the studies with high risk of bias, the magnitude of the pooled benefits on SBP and DBP increased to - 3.62 mmHg (95 % CI: - 6.69, - 0.56) and - 1.35 mmHg (95 % CI: - 2.29, - 0.41), respectively. However, there are several barriers to the use of PACs, specifically in low- and middle-income countries (LMICs), such as the initial purchase cost and filter replacements. There may be several avenues to help overcome these economic burdens and improve cost effectiveness, such as implementing government or other subsidized programs to distribute PACs targeting vulnerable and higher-risk individuals. We propose that environmental health researchers and healthcare providers should be better trained to educate the public regarding the use of PACs to reduce the impacts of PM2.5 on cardiometabolic diseases globally.

Application of an Ultra-Low-Cost Passive Sampler for Light-Absorbing Carbon in Mongolia.

Low-cost, long-term measures of air pollution concentrations are often needed for epidemiological studies and policy analyses of household air pollution. The Washington passive sampler (WPS), an ultra-low-cost method for measuring the long-term average levels of light-absorbing carbon (LAC) air pollution, uses digital images to measure the changes in the reflectance of a passively exposed paper filter. A prior publication on WPS reported high precision and reproducibility. Here, we deployed three methods to each of 10 households in Ulaanbaatar, Mongolia: one PurpleAir for PM2.5; two ultrasonic personal aerosol samplers (UPAS) with quartz filters for the thermal-optical analysis of elemental carbon (EC); and two WPS for LAC. We compared multiple rounds of 4-week-average measurements. The analyses calibrating the LAC to the elemental carbon measurement suggest that 1 µg of EC/m3 corresponds to 62 PI/month (R2 = 0.83). The EC-LAC calibration curve indicates an accuracy (root-mean-square error) of 3.1 µg of EC/m3, or ~21% of the average elemental carbon concentration. The RMSE values observed here for the WPS are comparable to the reported accuracy levels for other methods, including reference methods. Based on the precision and accuracy results shown here, as well as the increased simplicity of deployment, the WPS may merit further consideration for studying air quality in homes that use solid fuels.

Immigrant Legal Status among Essential Frontline Workers in the United States during the COVID-19 Pandemic Era.

Emerging evidence suggests that the COVID-19 pandemic has extracted a substantial toll on immigrant communities in the United States, due in part to increased potential risk of exposure for immigrants to COVID-19 in the workplace. In this article, we use federal guidance on which industries in the United States were designated essential during the COVID-19 pandemic, information about the ability to work remotely, and data from the 2019 American Community Survey to estimate the distribution of essential frontline workers by nativity and immigrant legal status. Central to our analysis is a proxy measure of working in the primary or secondary sector of the segmented labor market. Our results indicate that a larger proportion of foreign-born workers are essential frontline workers compared to native-born workers and that 70 percent of unauthorized immigrant workers are essential frontline workers. Disparities in essential frontline worker status are most pronounced for unauthorized immigrant workers and native-born workers in the secondary sector of the labor market. These results suggest that larger proportions of foreign-born workers, and especially unauthorized immigrant workers, face greater risk of potential exposure to COVID-19 in the workplace than native-born workers. Social determinants of health such as lack of access to health insurance and living in overcrowded housing indicate that unauthorized immigrant essential frontline workers may be more vulnerable to poor health outcomes related to COVID-19 than other groups of essential frontline workers. These findings help to provide a plausible explanation for why COVID-19 mortality rates for immigrants are higher than mortality rates for native-born residents.

Outcomes of Talar Osteochondral and Transchondral Lesions Using an Algorithmic Approach Based on Size, Location, and Subchondral Plate Integrity: A 10-Year Study on 204 Lesions.

The management of transchondral and osteochondral talar lesions has evolved, with microfracturing originally considered the best initial treatment. Despite talar lesions being a tri-dimensional defect, most studies use 2-dimensional parameters to grade them. We propose in this study that tri-dimensional sizing may be more appropriate in evaluation for treatment. The present study evaluated the outcomes of treatment of talar lesions performed by a single surgeon, creating and using an algorithm based on volume, location, and integrity of the subchondral plate. The lesions were classified as "small" (up to 125 mm3), "medium" (125 mm3-1500 mm3), and "large" (>1500 mm3) based upon evaluation of the preoperative magnetic resonance imagining. Location of the lesion was also noted on a 9-region grid pattern of the talar dome. These 3 parameters dictated whether a lesion required microfracturing or retrograde drilling, autogenous or allogenous bone graft, and whether an open versus an arthroscopic approach was required. Over a 10-year period, surgery was performed on 204 lesions. Overall, the average time to return to activity was 7.93 ± 5.00 (range 2-36) months. The average preoperative American Orthopaedic Foot and Ankle score was 76.44 ± 10.98 (range 52-86), and the average postoperative American Orthopaedic Foot and Ankle score was 96.12 ± 3.46 (range 81-100), p = .0001. By using the proposed algorithm, the outcome and return to activity for most patients can be better predicted, regardless of the size or location of the osteochondral lesion. The treatment algorithm implemented in the present investigation yielded overall acceptable results, with only 7 of the 204 lesions needing additional surgery.

Trivalent sulfonium compounds (TSCs): Tetrahydrothiophene-based amphiphiles exhibit similar antimicrobial activity to analogous ammonium-based amphiphiles.

Recent advances in the development of quaternary ammonium compounds (QACs) have focused on new structural motifs to increase bioactivity, but significantly less studied has been the change from ammonium- to sulfonium-based disinfectants. Herein, we report the synthesis of structurally analogous series of quaternary ammonium and trivalent sulfonium compounds (TSCs). The bioactivity profiles of these compounds generally mirror each other, and the antibacterial activity of sulfonium-based THT-18 was found to be comparable to the commercial disinfectant, BAC. The development of these compounds presents a new avenue for further study of disinfectants to combat the growing threat of bacterial resistance.

Portable HEPA filter air cleaner use during pregnancy and children's behavior problem scores: a secondary analysis of the UGAAR randomized controlled trial.

BACKGROUND: Developmental exposure to particulate matter (PM) air pollution may impair children's behaviors. Our objectives were to quantify the impact of reducing indoor PM using portable HEPA filter air cleaners during pregnancy on behavioral problems in children and to assess associations between indoor fine PM (PM2.5) concentrations during pregnancy and children's behavior. METHODS: This is a secondary analysis of a single-blind parallel-group randomized controlled trial in which we randomly assigned 540 non-smoking pregnant women to receive 1 or 2 HEPA filter air cleaners or no air cleaners. We administered the Behavior Assessment System for Children (BASC-3) to caregivers when children were a mean age of 23 months, and again at a mean age of 48 months. Primary outcomes were the four BASC-3 composite scales: externalizing problems, internalizing problems, adaptive skills, and the behavioral symptoms index. We imputed missing data using multiple imputation with chained equations. The primary analysis was by intention-to-treat. In a secondary analysis, we evaluated associations between BASC-3 composite indices and modeled trimester-specific PM2.5 concentrations inside residences. RESULTS: We enrolled participants at a median of 11 weeks gestation. After excluding miscarriages, still births and neonatal deaths, our analysis included 478 children (233 control and 245 intervention). We observed no differences in the mean BASC-3 scores between treatment groups. An interquartile increase (20.1 µg/m3) in first trimester PM2.5 concentration was associated with higher externalizing problem scores (2.4 units, 95% CI: 0.7, 4.1), higher internalizing problem scores (2.4 units, 95% CI: 0.7, 4.0), lower adaptive skills scores (-1.5 units, 95% CI: -3.0, 0.0), and higher behavior symptoms index scores (2.3 units, 95% CI: 0.7, 3.9). Third trimester PM2.5 concentrations were also associated with some behavioral indices at age 4, but effect estimates were smaller. No significant associations were observed with PM2.5 concentrations during the second trimester or for any of the BASC indices when children were 2 years old. CONCLUSION: We found no benefit of reducing indoor particulate air pollution during pregnancy on parent-reported behaviors in children. Associations between indoor PM2.5 concentrations in the first trimester and behavioral scores among 4-year old children suggest that it may be necessary to intervene early in pregnancy to protect children, but these exploratory findings should be interpreted cautiously. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01741051.

The Impact of Color Fidelity on Evaluation of Patients in the Outpatient Dermatologic Setting.

BACKGROUND AND OBJECTIVES: To demonstrate that high color fidelity light-emitting diode (LED) sources are preferred by dermatologists for the evaluation of patients during standard-of-care, outpatient visits when compared to low color fidelity LED sources similar to fluorescent lighting. STUDY DESIGN/MATERIALS AND METHODS: Three different LED sources were installed in exam rooms at a single, academic, medical institution (low color fidelity [82 color rendering index (CRI)] similar to fluorescent lighting, and high color fidelity [97 CRI and 96+red CRI]). A cross-sectional survey study was conducted in three parts. Naturalness (i.e. ability to reproduce natural, daylight conditions), effectiveness, color contrast, comfort, and overall performance of each LED source were rated on a 5-point scale from 0 to 4 with 0 being the worse, and 4 being the best. The first part included a survey of board-certified dermatologists (n = 3) assessing their visual experience while clinically evaluating a subset of patients during standard-of-care outpatient visits. The second survey was completed by dermatologic medical providers (n = 55) at three separate monthly departmental Grand Rounds sessions in which standardized patients were evaluated with the LED sources. Lastly, patients (n = 75) finished a survey assessing the comfort level of the LED sources. RESULTS: In the first part of the study, all dermatologists significantly preferred the high color fidelity sources over low color fidelity sources based on all five evaluation criteria, with two preferring the 97 CRI LED source overall, while the third dermatologist favored 96+red CRI. Assessments provided by the 55 participants at Grand Rounds demonstrated that the 97 CRI was most "liked." Patients also preferred the high color fidelity LED source, reporting the 96+red CRI source was the "most comfortable." CONCLUSION: Dermatologists, dermatologists-in-training and mid-level providers significantly prefer high color fidelity LED sources for outpatient evaluation of dermatologist patients in enclosed spaces, rating them the more natural, effective, comfortable, and providing superior color contrast than low color sources. Patients also favor high color fidelity LED sources as being the most comfortable in the clinic room. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Global estimates of mortality associated with long-term exposure to outdoor fine particulate matter.

Exposure to ambient fine particulate matter (PM2.5) is a major global health concern. Quantitative estimates of attributable mortality are based on disease-specific hazard ratio models that incorporate risk information from multiple PM2.5 sources (outdoor and indoor air pollution from use of solid fuels and secondhand and active smoking), requiring assumptions about equivalent exposure and toxicity. We relax these contentious assumptions by constructing a PM2.5-mortality hazard ratio function based only on cohort studies of outdoor air pollution that covers the global exposure range. We modeled the shape of the association between PM2.5 and nonaccidental mortality using data from 41 cohorts from 16 countries-the Global Exposure Mortality Model (GEMM). We then constructed GEMMs for five specific causes of death examined by the global burden of disease (GBD). The GEMM predicts 8.9 million [95% confidence interval (CI): 7.5-10.3] deaths in 2015, a figure 30% larger than that predicted by the sum of deaths among the five specific causes (6.9; 95% CI: 4.9-8.5) and 120% larger than the risk function used in the GBD (4.0; 95% CI: 3.3-4.8). Differences between the GEMM and GBD risk functions are larger for a 20% reduction in concentrations, with the GEMM predicting 220% higher excess deaths. These results suggest that PM2.5 exposure may be related to additional causes of death than the five considered by the GBD and that incorporation of risk information from other, nonoutdoor, particle sources leads to underestimation of disease burden, especially at higher concentrations.

The "LOOMING DISASTER" for higher education: how commercial rankers use social media to amplify and foster affect.

Despite the ubiquity of global university rankings coverage in media and academia, a concerted attempt to investigate the role of social media in ranking entrepreneurship remains absent. By drawing on an affect lens, we critically examine the social media activities of two commercial rankers: Times Higher Education (THE) and Quacquarelli Symonds Ltd (QS). Based on an analysis of THE's Twitter feed and QS' Facebook page between January and June 2020, we illuminate how rankers use social media for affective storytelling to frame and sell their expertise within global HE. First, we demonstrate how THE uses Twitter to engage an audience of institutions, governments, and administrators, reinforcing universities' increasingly aggressive behavior as market competitors. Next, we show how QS engages a student-oriented audience on Facebook, furthering the role of students as consumers. Before and during the COVID pandemic, we observed that both rankers amplified and mobilized precarity associated with performance and participation, selling hope to targeted audiences to market their expertise as solutions-a strategy that remained amidst the global pandemic. Based on our observation of the front stage of rankers' social media activities, we argue that rankers' deployment of social media as a form of affective infrastructure is conducive to further sustaining, diffusing, and normalizing rankings in HE globally.

Circulating microbial small RNAs are altered in patients with rheumatoid arthritis.

OBJECTIVES: To determine if plasma microbial small RNAs (sRNAs) are altered in patients with rheumatoid arthritis (RA) compared with control subjects, associated with RA disease-related features, and altered by disease-modifying antirheumatic drugs (DMARDs). METHODS: sRNA sequencing was performed on plasma from 165 patients with RA and 90 matched controls and a separate cohort of 70 patients with RA before and after starting a DMARD. Genome alignments for RA-associated bacteria, representative bacterial and fungal human microbiome genomes and environmental bacteria were performed. Microbial genome counts and individual sRNAs were compared across groups and correlated with disease features. False discovery rate was set at 0.05. RESULTS: Genome counts of Lactobacillus salivarius, Anaerobaculum hydrogeniformans, Staphylococcus epidermidis, Staphylococcus aureus, Paenisporosarcina spp, Facklamia hominis, Sphingobacterium spiritivorum, Lentibacillus amyloliquefaciens, Geobacillus spp, and Pseudomonas fluorescens were significantly decreased in the plasma of RA compared with control subjects. Three microbial transfer RNA-derived sRNAs were increased in RA versus controls and inversely associated with disease activity. Higher total microbial sRNA reads were associated with lower disease activity in RA. Baseline total microbial sRNAs were threefold higher among patients who improved with DMARD versus those who did not but did not change significantly after 6 months of treatment. CONCLUSION: Plasma microbial sRNA composition is altered in RA versus control subjects and associated with some measures of RA disease activity. DMARD treatment does not alter microbial sRNA abundance or composition, but increased abundance of microbial sRNAs at baseline was associated with disease activity improvement at 6 months.

Dscam1 Forms a Complex with Robo1 and the N-Terminal Fragment of Slit to Promote the Growth of Longitudinal Axons.

The Slit protein is a major midline repellent for central nervous system (CNS) axons. In vivo, Slit is proteolytically cleaved into N- and C-terminal fragments, but the biological significance of this is unknown. Analysis in the Drosophila ventral nerve cord of a slit allele (slit-UC) that cannot be cleaved revealed that midline repulsion is still present but longitudinal axon guidance is disrupted, particularly across segment boundaries. Double mutants for the Slit receptors Dscam1 and robo1 strongly resemble the slit-UC phenotype, suggesting they cooperate in longitudinal axon guidance, and through biochemical approaches, we found that Dscam1 and Robo1 form a complex dependent on Slit-N. In contrast, Robo1 binding alone shows a preference for full-length Slit, whereas Dscam1 only binds Slit-N. Using a variety of transgenes, we demonstrated that Dscam1 appears to modify the output of Robo/Slit complexes so that signaling is no longer repulsive. Our data suggest that the complex is promoting longitudinal axon growth across the segment boundary. The ability of Dscam1 to modify the output of other receptors in a ligand-dependent fashion may be a general principle for Dscam proteins.

Two-Dimensional White-Light Spectroscopy Using Supercontinuum from an All-Normal Dispersion Photonic Crystal Fiber Pumped by a 70 MHz Yb Fiber Oscillator.

We report on a new broadband, ultrafast two-dimensional white-light (2DWL) spectrometer that utilizes a supercontinuum pump and a supercontinuum probe generated with a ytterbium fiber oscillator and an all-normal dispersion photonic crystal fiber (ANDi PCF). We demonstrate compression of the supercontinuum to sub-20 fs and the ability to collect high quality 2D spectra on films of single-walled carbon nanotubes. Two spectrometer designs are investigated. Supercontinuum from ANDi PCF provides a means to generate broadband pulse sequences for multidimensional spectroscopy without the need for an optical parametric amplifier.

Coal smoke, gestational cadmium exposure, and fetal growth.

BACKGROUND: Gestational cadmium exposure may impair fetal growth. Coal smoke has largely been unexplored as a source of cadmium exposure. We investigated the relationship between gestational cadmium exposure and fetal growth, and assessed coal smoke as a potential source of airborne cadmium, among non-smoking pregnant women in Ulaanbaatar, Mongolia, where coal combustion in home heating stoves is a major source of outdoor and indoor air pollution. METHODS: This observational study was nested within the Ulaanbaatar Gestation and Air Pollution Research (UGAAR) study, a randomized controlled trial of portable high efficiency particulate air (HEPA) filter air cleaner use during pregnancy, fetal growth, and early childhood development. We measured third trimester blood cadmium concentrations in 374 out of 465 participants who had a live birth. We used multiple linear and logistic regression to assess the relationships between log2-transformed maternal blood cadmium concentrations and birth weight, length, head circumference, ponderal index, low birth weight, small for gestational age, and preterm birth in crude and adjusted models. We also evaluated the relationships between log2-transformed blood cadmium concentrations and the density of coal-burning stoves within 5000 m of each participant's apartment as a proxy of coal smoke emissions from home heating stoves. RESULTS: The median (25th,75th percentile) blood cadmium concentration was 0.20 (0.15, 0.29) µg/L. A doubling of blood cadmium was associated with a 95 g (95% CI: 34, 155 g) reduction in birth weight in adjusted models. An interquartile range increase in coal stove density (from 3.4 to 4.9 gers/hectare) surrounding participants' apartments was associated with a 12.2% (95% CI: 0.3, 25.6%) increase in blood cadmium concentrations. CONCLUSIONS: Gestational cadmium exposure was associated with reduced birth weight. In settings where coal is a widely used fuel, cadmium may play a role in the putative association between air pollution and impaired fetal growth.

More QACs, more questions: Recent advances in structure activity relationships and hurdles in understanding resistance mechanisms.

Quaternary ammonium compounds (QACs) are a class of antimicrobials that have been around for over a century; nevertheless, they have found continued renewal in the structures to which they can be appended. Ranging from antimicrobial polymers to adding novel modes of action to existing antibiotics, QACs have found ongoing use due to their potent properties. However, resistance against QACs has begun to emerge, and the mechanism of resistance is still only partially understood. In this review, we aim to summarize the current state of the field and what is known about the mechanisms of resistance so that the QACs of the future can be designed to be evermore efficacious and utilized to unearth the remaining mysteries that surround bacteria's resistance to them.

Optimizing 802.15.4 Outdoor IoT Sensor Networks for Aerial Data Collection.

Rural IoT sensor networks, prevalent in environmental monitoring and precision agriculture, commonly operate over some variant of the IEEE 802.15.4 standard. Data collection from these networks is often challenging, as they may be deployed in remote regions where existing backhaul infrastructure is expensive or absent. With the commercial and industrial success of Unmanned Aircraft Systems (UAS), there is understandable interest in using UASs for delay tolerant data collection from 802.15.4 IoT sensor networks. In this study, we investigate how to optimize 802.15.4 networks for aerial data collection, which, unlike other wireless standards, has not received rigorous evaluation for three-dimensional aerial communication. We analyze experimental measurements from an outdoor aerial testbed, examining how factors, such as antenna orientation, altitude, antenna placement, and obstruction, affect signal strength and packet reception rate. In our analysis, we model and predict the quality of service for aerial data collection, based on these network configuration variables, and contrast that with the Received Signal Strength Indication (RSSI)-a commonly used signal strength metric. We find that network configuration plays a significant role in network quality, which RSSI, a mediator variable, struggles to account for in the presence of high packet loss. We conclude with a discussion of strategies for optimizing sensor network configuration for aerial data collection, in light of our results.