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Non-suppressible HIV-1 viremia (NSV) is defined as persistent low-level viremia on antiretroviral therapy (ART) without evidence of ART non-adherence or significant drug resistance. Unraveling the mechanisms behind NSV would broaden our understanding of HIV-1 persistence. Here we analyzed plasma virus sequences in eight ART-treated individuals with NSV (88% male) and show that they are composed of large clones without evidence of viral evolution over time in those with longitudinal samples. We defined proviruses that match plasma HIV-1 RNA sequences as ‘producer proviruses’, and those that did not as ‘non-producer proviruses’. Non-suppressible viremia arose from expanded clones of producer proviruses that were significantly larger than the genome-intact proviral reservoir of ART-suppressed individuals. Integration sites of producer proviruses were enriched in proximity to the activating H3K36me3 epigenetic mark. CD4+T cells from participants with NSV demonstrated upregulation of anti-apoptotic genes and downregulation of pro-apoptotic and type I/II interferon-related pathways. Furthermore, participants with NSV showed significantly lower HIV-specific CD8+T cell responses compared with untreated viremic controllers with similar viral loads. We identified potential critical host and viral mediators of NSV that may represent targets to disrupt HIV-1 persistence.

BackgroundAlthough genome-wide association studies (GWAS) have identified many genomic regions associated with idiopathic pulmonary fibrosis (IPF), the causal genes and functions remain largely unknown. Many single-cell expression data have become available for IPF, and there is increasing evidence suggesting a shared genetic basis between IPF and other diseases.MethodsWe conducted integrative analyses to improve the power of GWAS. First, we calculated global and local genetic correlations to identify IPF genetically associated traits and local regions. Then, we prioritised candidate genes contributing to local genetic correlation. Second, we performed transcriptome-wide association analysis (TWAS) of 44 tissues to identify candidate genes whose genetically predicted expression level is associated with IPF. To replicate our findings and investigate the regulatory role of the transcription factors (TF) in identified candidate genes, we first conducted the heritability enrichment analysis in TF binding sites. Then, we examined the enrichment of the TF target genes in cell-type-specific differentially expressed genes (DEGs) identified from single-cell expression data of IPF and healthy lung samples.FindingsWe identified 12 candidate genes across 13 genomic regions using local genetic correlation, including the POT1locus (p value=0.00041), which contained variants with protective effects on lung cancer but increasing IPF risk. We identified another 13 novel genes using TWAS. Two TFs, MAFKand SMAD2, showed significant enrichment in both partitioned heritability and cell-type-specific DEGs.InterpretationOur integrative analysis identified new genes for IPF susceptibility and expanded the understanding of the complex genetic architecture and disease mechanism of IPF.

Vegetative filter strip characteristics such as perenniality drive hydrology and subsequent ecosystem services. However, the extent and the potential for forage–biomass crops to improve water quality, provide fodder, and optimize nutrient cycling in multifunctional systems is unknown. We evaluated (a) how species, perenniality, and plant community composition are linked to water quality; and (b) the multiuse forage–biomass potential of filter strips. Whole plots were species [eastern gamagrass (Tripsacum dactyloides), Kernza [or intermediate wheatgrass (Thinopyrum intermedium)], silphium (Silphium integrifolium), switchgrass (Panicum virgatum), and winter wheat (Triticum aestivum)], with split‐plots receiving 0 or 5.6 Mg ha−1broiler litter. Rainfall simulations were conducted at 5 cm h−1(until 30 min of continuous runoff) in summer and fall of 2019 and 2021 with dual forage and biomass harvests occurring 2019–2021. Kernza and silphium had the lowest biomass regrowth after forage harvests relative to native grasses, suggesting they would not be ideal multifunctional forage–bioenergy crops. Among all soil–plant–water variables, canonical correlations indicate poultry litter (.97), and soil phosphorus saturation (.77) were the most influential variables for water quality. Water quality score, FWQ, which is inversely related to runoff water quality, was lowest for switchgrass (0.03) and greatest (P≥ .05) for eastern gamagrass and wheat (1.77 and 3.33, respectively), but not different from Kernza (0.98) and silphium (0.31). Therefore, switchgrass resulted in the best water quality scores and highest forage–biomass yields, with Kernza and silphium also showing promise for reducing sediment and nutrient loads following poultry litter applications in multifunctional filter strip systems. Filter strip characteristics drive surface hydrology and subsequent ecosystem services. Greatest multiuse (forage–biomass filter strip) yields occurred for switchgrass. Poultry litter applications and soil P saturation were most correlated with water quality. Perennial crops (excluding eastern gamagrass) improved water quality. Switchgrass had the highest water quality and biomass yields, indicating greatest multiuse filter strip potential.

Poultry litter is generated in large quantities throughout the southeastern United States and is an excellent nutrient source for increasing crop yields. However, surface applications result in nutrient losses to air, soil, and water. Subsurface banding poultry litter is a promising technology for reducing nutrient losses to surface and groundwater, but information is needed on optimum crop seeding distance from bands. This study evaluated edamame [Glycine max(L.) Merr. ‘Edamame’] yield (residue, pod, and total plant), crop quality, and leaf greenness. Subsurface banded poultry litter and crop row distances (13, 25, and 38 cm) were compared with surface‐applied poultry litter (all received 168 kg ha−1total N) under irrigated and nonirrigated conditions from 2019 to 2020. Both chlorophyll and edamame total yields were greatest (P≤ .05) under subsurface banding litter, relative to surface applications, regardless of distance. Overall, greatest total crop yields were observed for 13‐ and 25‐cm banding distances under irrigation and the 38‐cm distance, irrespective of irrigation, relative to surface applications. Residue nutritive value for the 13‐cm distance was greater under irrigation than dryland. Both systems provided high levels of nutritive residual mass, thus edamame could be used as a vegetable crop and a forage following harvest. Overall, subsurface banding poultry litter in conservation tillage systems is a viable replacement to surface applications for edamame production (vegetable and fodder), particularly in organic systems. Results can be used to develop nutrient management plans for organic edamame and other specialty crop production systems in the Mid‐South. Subsurface banding resulted in greater leaf greenness and yield compared with surface litter.Edamame can serve as a multifunctional crop for use as an organic vegetable and fodder.Subsurface banding litter at all distances were optimum for organic total edamame yields.

Patients with sarcoidosis who develop severe clinical phenotypes of pulmonary fibrosis or multiorgan disease experience debilitating symptoms, with fatigue being a common chief complaint. Studies that have investigated this patient-related outcome measure (PROM) have used the Fatigue Assessment Scale (FAS), a self-reported questionnaire that reflects mental and physical domains. Despite extensive work, its cause is unknown and treatment options remain limited. Previously, we showed that the plasma of patients with sarcoidosis with extrapulmonary disease endorsing fatigue was enriched for mitochondrial DNA (mtDNA), a ligand for the innate immune receptor toll-like receptor 9 (TLR9). Through our cross-disciplinary platform, we investigated a relationship between sarcoidosis-induced fatigue and circulating mtDNA.

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2and CTSLacross 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2and CTSLare coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial–macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.

In a partnership with the nationally respected Children's Defense Fund, AASA is encouraging schools to enroll eligible students in Medicaid or the state's Children's Health Insurance Program. Through a grant [...]

We use a multi‐year record of Pandora‐derived NO2total column abundance in Boston to examine the influence of atmospheric transport on column NO2and its surface concentrations during the warm season in a coastal urban environment. We derive tropospheric NO2estimates from the total column with a measurement‐model fusion approach using near‐real‐time estimates of stratospheric NO2from NASA's Goddard Earth Observing System Composition Forecast model system and find the average influence of stratospheric NO2at this urban site can be 30%–70% depending on season and time of day. Sea breeze days tend to exhibit rapid temporal variability in the column that which can go in the opposite direction of changes in surface NO2concentrations. By comparing tropospheric NO2with surface concentrations, we constrain the role of boundary layer entrainment processes in the evolution of surface NO2concentrations, while highlighting the value of column measurements in identifying sea breeze frontal dynamics. We estimate an apparent equal mixing layer height of NO2and infer that surface NOxemissions remain concentrated near the surface regardless of atmospheric stability regime. When comparing the Pandora‐ to TROPOMI‐derived column NO2measurements, we find that sea breeze days present a unique challenge likely due to higher spatial heterogeneity in NO2and the meteorology involved that is not well represented in retrieval inputs. Our observations provide new insights into column and surface variability of NO2which will be relevant to interpreting geostationary observations, especially in coastal urban locations. Relating satellite‐derived observations of nitrogen dioxide (NO2) to ground‐level air quality has long been an area of research with important applications to human and environmental welfare. Here, we use new remote sensing observations from ground‐ and satellite‐based instruments, along with ground‐level air quality monitoring and meteorological observations, to gain new insight into the relationship of NO2total column abundance and surface concentrations in a costal urban environment. We show how the total columns (the NO2between the surface and top of the atmosphere) derived from remote sensing are sensitive to different processes than surface concentrations (the amount of NO2at a point near the surface), which complicate the interpretation of surface air quality from satellite observations. We also find evidence that the mixing of surface emissions in our urban environment is slow relative to the NOxlifetime even under conditions when the boundary layer is expected to be well‐mixed. We find that sea breeze systems common to coastal environments present particularly challenging circumstances, due to higher spatial and temporal variability in pollutant concentrations. Our results should provide some insights into the interpretation of new geostationary air quality observations. Tropospheric NO2column measurements capture rapid changes in horizontal advection of pollutionCollocated column and in situ measurements constrain the dominant role of vertical entrainment in NO2surface concentrationsSea breezes pose a challenge to satellite retrievals of NO2due to heterogeneity in NO2and meteorology Tropospheric NO2column measurements capture rapid changes in horizontal advection of pollution Collocated column and in situ measurements constrain the dominant role of vertical entrainment in NO2surface concentrations Sea breezes pose a challenge to satellite retrievals of NO2due to heterogeneity in NO2and meteorology

Coastal urban environments face unique challenges associated with air quality‐meteorology interactions. In this study, high resolution chemical transport modeling over the Greater Boston area was performed to improve our understanding of sea breezes impacts on the spatiotemporal variability of primary and secondary pollutants. We perform WRF‐Chem simulations at 3 km resolution over June 22 to 10 July 2019 (a period that included 10 sea breeze occurrences), and use Pandora tropospheric NO2column, surface air quality monitoring, and vertical meteorological aircraft profiles for evaluation. The model generally reproduces observed spatiotemporal variability of air pollution during sea breezes well. Tropospheric columns of NO2predicted by the model and observed by the Pandora instrument show that sea breezes are associated with rapid increases and steep gradients in tropospheric NO2and confirm accumulation of local primary emissions. Spatial heterogeneity in tropospheric NO2is strongly governed by inland penetration lengths of the sea breeze front. Process diagnostics show that three sea‐breeze days where O3observations recorded hourly concentrations >70 ppb have both efficient net chemical O3production in the boundary layer (>10 ppb/hr) and rapid O3convergence in the near‐surface convergence zone (>20 ppb/hr). During sea breezes, interactions between photochemistry, the convergence zone inland penetration, and urban NOxtitration effects, contribute to strong heterogeneity and high O3inland that is not captured by the current monitoring network. We discuss monitoring needs and model applications for the sea breeze scenarios, with broad implications for air quality monitoring in coastal urban environments. The sea breeze is a local meteorological system that brings air from the sea over the land during the day. In areas that usually experience offshore winds, this means the system can recirculate early morning pollutant emissions back onshore later in the day. Understanding the behavior of air pollutants in coastal urban environments is essential for air quality management, but land‐sea breeze circulations are characterized by fine scale features and rapid changes in pollution levels that pose challenges for traditional monitoring and satellite retrievals. In the Greater Boston area, we use highly resolved information from a regional chemical transport model combined with observational assets to examine pollutant behavior and model performance. We find new evidence of underestimated regional ozone pollution and nitrogen dioxide column spatial variability associated with sea breezes. This variability is governed by how far the sea breeze penetrates inland, but is also affected by interactions between chemistry and atmospheric dynamic that are not well captured by current monitoring and coarse resolution models. Our results provide valuable insights for future ground‐based and satellite remote sensing monitoring, highlighting that customized strategies for monitoring coastal urban air quality are required from high‐resolution models constrained by carefully allocated observations. High resolution WRF‐Chem modeling reproduces observed spatiotemporal variability of NO2and O3during sea breezes in the Greater Boston areaModel results suggest high O3pollution and NO2column spatial variability associated with sea breezes is not captured by current monitoringMonitoring coastal urban air quality requires customized strategies with high‐resolution modeling and well‐allocated observations High resolution WRF‐Chem modeling reproduces observed spatiotemporal variability of NO2and O3during sea breezes in the Greater Boston area Model results suggest high O3pollution and NO2column spatial variability associated with sea breezes is not captured by current monitoring Monitoring coastal urban air quality requires customized strategies with high‐resolution modeling and well‐allocated observations

Most cell types in multicellular organisms can perform multiple functions. However, not all functions can be optimally performed simultaneously by the same cells. Functions incompatible at the level of individual cells can be performed at the cell population level, where cells divide labor and specialize in different functions. Division of labor can arise due to instruction by tissue environment or through self-organization. Here, we develop a computational framework to investigate the contribution of these mechanisms to division of labor within a cell-type population. By optimizing collective cellular task performance under trade-offs, we find that distinguishable expression patterns can emerge from cell-cell interactions versus instructive signals. We propose a method to construct ligand-receptor networks between specialist cells and use it to infer division-of-labor mechanisms from single-cell RNA sequencing (RNA-seq) and spatial transcriptomics data of stromal, epithelial, and immune cells. Our framework can be used to characterize the complexity of cell interactions within tissues.

Presents letters to the editor referencing articles and topic discussed in previous issues. "Uranium Mystery in the Colorado Basin," which focused on the assertion that the U.S. Atomic Energy Commission opposes the release of a Public Health Service Report on uranium mill tailings; Separation of U.S. Vice President Hubert Humphrey from the liberal wing; "The Case Against a Tax Increase," which argued against a tax increase in the U.S.

Barbara Best--my former co-director in this joint AASA/CDF venture and now associate director for student and fellows programs and special projects at Harvard's Kennedy School--used to tell me that we [...]

This study evaluates the ability of users to self-install a smart home in a box (SHiB) intended for use by a senior population. SHiB is a ubiquitous system, developed by the Washington State University Center for Advanced Studies in Adaptive Systems (CASAS). Participants involved in this study are from the greater Palouse region of Washington State, and there are 13 participants in the study with an average age of 69.23. The SHiB package, which included several different types of components to collect and transmit sensor data, was given to participants to self-install. After installation of the SHiB, the participants were visited by researchers for a check of the installation. The researchers evaluated how well the sensors were installed and asked the resident questions about the installation process to help improve the SHiB design. The results indicate strengths and weaknesses of the SHiB design. Indoor motion tracking sensors are installed with high success rate, low installation success rate was found for door sensors and setting up the Internet server.

A previously published report by these authors on the impact in the United States of recession on children's health emphasized four points: 1) available monitoring systems are not adequate for reporting on the health of children in a timely fashion; 2) the monitoring of maternal and child health must emphasize data on population subgroups, i.e., minorities, the poor and those hardest hit by recession; 3) the health of poor children is adversely affected and their numbers dramatically increased during the recession of 1981–82; and 4) comparisons between the recession of 1974–75 and that of 1981–82 suggest that expansion of health services and social support systems during the recession of 1974–75 had a cushioning effect that protected the health of children, while the curtailment of many of these programs during the 1981–82 recession is associated with adverse health trends, especially among the most vulnerable population subgroups.Data on these issues are appreciably better now than they were nine months ago, thus further validating the points made above. As with the previous report, officially released current data are abundant for economic indicators (even for early 1984), but are sparse for health status indicators. The previous report also observed that the health status of children is influenced by interdependent and interlocking factors that include economic well-being and access to health services and social supports. A new analysis attempts to unlock those relationships and measure the impact of lost welfare benefits, implemented as a result of the Omnibus Reconciliation Act of 1981 (OBRA), and the separate impact of the serious recession of 1981–82. That analysis shows the poverty rate for children increased by 7.6 percentage points between 1981 and 1982. Approximately 60 percent of the increase is attributable to the recession and 40 percent to social policy changes effected after 1981.

This is a review of the United States experience with issues of child health and services as they relate to changes in economic trends. No existing data systems are entirely adequate for reporting on the current health status of children. An important consideration for the monitoring of children's health in the United States is the status of subgroups such as those who are disadvantaged for reasons of poverty, discrimination or geographic isolation. Ample evidence confirms that children living in poverty suffer adverse health consequences and that the proportion of children living in poverty in the United States has increased steadily since 1975 and dramatically since 1981. Most measures of health status and health risks for children show steady improvements throughout the 1970s. The exercise of public responsibility for financing and providing essential services and supports held constant or improved during this period, especially during the recession of 1974–75. The health status and risks for children since 1981 appear to be adversely affected which must be attributed to a combination of circumstances that include serious recession, increased poverty rates for households with children and diminished health benefits and social support services. These findings suggest that when either local or widespread economic reversals are anticipated, health services and social supports for children need to be expanded rather than contracted.

Presents letters to the editor referencing articles and topics discussed in previous issues. Purpose of the Negro press; Military domination of the U.S. in China; Concern of the Poles on the fate of the Oder-Niesse line.

Cell-based therapies have shown promise for treating myriad chronic pulmonary diseases through direct application of epithelial progenitors or by way of engineered tissue grafts or whole organs. To elucidate environmental effects on epithelial regenerative outcomes in vitro, here, we isolate and culture a population of pharmacologically expanded basal cells (peBCs) from rat tracheas. At peak basal marker expression, we simultaneously split peBCs into four in vitroplatforms: organoid, air-liquid interface (ALI), engineered trachea, and engineered lung. Following differentiation, these samples are evaluated using single-cell RNA sequencing (scRNA-seq) and computational pipelines are developed to compare samples both globally and at the population level. A sample of native rat tracheal epithelium is also evaluated by scRNA-seq as a control for engineered epithelium. Overall, this work identifies platform-specific effects that support the use of engineered models to achieve the most physiologic differential outcomes in pulmonary epithelial regenerative applications.

Presents letters to the editor about various happenings in the U.S. Criticism of playwright Eugene Ionesco; Information on American electioneering; Hostility shown by Cubans.

Presents letters to the editor. Information on political conditions in Iran in 1964; Advantages of compact cars; Information on the Far Eastern policy of the U.S.

Presents several letters to the editor. Possible alternative for the member nations of the United Nations to maintain world peace; Possible solution to the housing problems in the U.S.; Description of some civil rights deprivations of minorities in the U.S.

Presents several letters to the editor. Comments on the article "Rafferty: New Hope of the Far Right," by Gene Marine; Discussion of a conference on peace and disarmament; Inability of members to achieve objectives of the conference.

Presents several letters to the editor regarding various issues of World politics. Suggestions for an article concerning German contributions to NATO; Comment on U.S. President John F. Kennedy's speech on nuclear incineration; Explanation for the aim of an article on narcotics addiction; Information of a follow-up study on Cuban missile crisis.

Presents several letters to the editor. Remarks made by the chairman of the section on military psychiatry in the annual meeting of the American Psychiatric Association at Chicago, Illinois; Comments of Colonel William Erwin Mayer on the subject of brainwashing; Details of the campaign conducted by George Romney, Governor of Michigan during gubernatorial elections.

Review: 93 refs.