Search

•Discovery of a novel CD39+T-cell population that predicts AIHA onset due to ICPi therapy.•This study demonstrates that apyrase acts as a novel therapeutic, effectively mitigating ICPi-induced AIHA.

Background Pervasive social and structural barriers—including national policies—inhibit HIV testing uptake among priority populations, including adolescents. We assessed the relationship between age-of-consent policies for HIV testing and adolescent HIV testing coverage in 51 low- and middle-income countries.Methods We pooled data from household surveys (2010–2020) and calculated the weighted country-level prevalence of lifetime HIV testing separately for adolescent girls and boys (ages 15–19). We then abstracted age-of-consent requirements for HIV testing across countries. Using multivariable linear regression, we estimated the average difference in national HIV testing coverage estimates for adolescent girls and boys by age-of-consent restrictions for HIV testing.Results National HIV testing coverage estimates ranged from 0.7% to 72.5% among girls (median: 18.0%) and 0% to 73.2% among boys (median: 7.5%) in Pakistan and Lesotho, respectively. In adjusted models, HIV testing coverage in countries requiring parental consent for individuals <18 years was, on average, 9.4 percentage-points (pp) lower (95% confidence interval [95%CI] −17.9pp to −0.9pp) among girls and 9.3pp lower (95%CI: −17.3pp to −1.2pp) among boys, relative to countries with less restrictive policies (age-of-consent: ≤16 years). Compared to countries with less restrictive (age-of-consent: ≤14 years) policies, HIV testing prevalence was significantly lower among girls (β−10.5pp, 95%CI: −19.7pp to −1.3pp) and boys (β−10.5pp, 95%CI –19.2pp to −1.8pp) in countries with more restrictive (age-of-consent: 18 years) parental consent requirements.Conclusions Age-of-consent policies are persistent obstacles to adolescent HIV testing. Repealing parental consent requirements for HIV testing is needed to expand coverage and accelerate progress towards global HIV treatment and prevention targets.

Environmental context Saccharides contribute substantially to dissolved organic carbon in the ocean and are enriched at the ocean surface. In this study, we demonstrate that saccharides are more enriched in persistent whitecap foam compared to the sea surface. The maturation of bubbles at the air–water interface is thus expected to enhance the enrichment of organic matter at the ocean surface and ultimately in the sea spray aerosol that forms when bubbles burst at the ocean surface. Rationale Organic matter accumulates at the ocean surface. Herein, we provide the first quantitative assessment of the enrichment of dissolved saccharides in persistent whitecap foam and compare this enrichment to the sea surface microlayer (SSML) during a 9 day mesocosm experiment involving a phytoplankton bloom generated in a Marine Aerosol Reference Tank (MART). Methodology Free monosaccharides were quantified directly, total saccharides were determined following mild acid hydrolysis and the oligo/polysaccharide component was determined as the difference between total and free monosaccharides. Results Total saccharides contributed a significant fraction of dissolved organic carbon (DOC), accounting for 13% of DOC in seawater, 27% in SSML and 31% in foam. Median enrichment factors (EFs), calculated as the ratio of the concentrations of saccharides relative to sodium in SSML or foam to that of seawater, ranged from 1.7 to 6.4 in SSML and 2.1–12.1 in foam. Based on median EFs, xylitol, mannitol, glucose, galactose, mannose, xylose, fucose, rhamnose and ribose were more enriched in foam than SSML. Discussion The greatest EFs for saccharides coincided with high chlorophyll levels, indicating increasing ocean surface enrichment of saccharides during phytoplankton blooms. Higher enrichments of organic matter in sea foam over the SSML indicate that surface active organic compounds become increasingly enriched on persistent bubble film surfaces. These findings help to explain how marine organic matter becomes highly enriched in sea spray aerosol that is generated by bursting bubbles at the ocean surface.

Satellite imagery and UAV (drone) photos taken at Lagash (modern Tell al-Hiba) after rainstorms and at times of elevated soil moisture show dense near-surface architecture that dates mostly to the Early Dynastic III period (c. 2600–2350 BCE) and covers several hundred hectares. Archaeological knowledge of Mesopotamian urban structure has mostly been limited to isolated excavated neighbourhoods, such as at third millennium BCE Tutub (Khafajah) or Eshnunna (Tell Asmar), and early second millennium BCE Ur (Tell al-Muqayyar). The morphology of Tell al-Hiba and the quality of the imagery sets create a unique situation that enables the reconstruction and comparison of neighbourhoods across almost the whole of the city of Lagash. Mapping of near-surface architectural remains, streets, and water features reveals a discontinuous city located within a watery, possibly marshy environment.

The Kathmandu Valley in Nepal suffers from unhealthy air quality, with mean pre-monsoon submicron particulate matter concentration (PM1) of 40 μg m−3and daily peaks over 75 μg m−3. A high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) measured ambient non-refractory submicron PM (NR-PM1) in a Kathmandu suburb in April 2015. The mean NR-PM1composition was 15.8 μg m−3(39.7%) organic aerosol (OA), 10.5 μg m−3(25.0%) BC, 8.4 μg m−3(21.1%) SO42−, 2.96 μg m−3(7.4%) NH4+, 1.22 μg m−3(3.1%) NO3−, and 0.92 μg m−3(2.3%) Cl−. NR-PM1exhibited a diurnal pattern with concentration maxima at 08:00 local standard time. Afternoon winds and an elevated planetary boundary layer then mitigated NR-PM1. Positive matrix factorization (PMF) of OA mass spectral data identified four primary source components: hydrocarbon-like OA (HOA, 15%), biomass burning OA (BBOA, 15%), trash burning OA (TBOA, 11%), a local sulfur-containing OA (sLOA, 7%), and three oxidized OA (OOA, 50%) factors. sLOA contains the ion C3HSO+, associated with emissions from coal used in brick kilns. Secondary aerosols account for 50% of all OA mass within the valley. Gas-phase carbon monoxide (CO), carbon dioxide (CO2), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), methane (CH4), and black and brown carbon (BC, BrC) measurements also characterized pollution in the valley. Composition, concentration, and source analysis from AMS-PMF and filter-based chemical mass balance measurements agree well (OC slope = 1.05, R2= 0.47). This work identifies and quantifies significant sources of PM1in the Kathmandu Valley and provides insight into the impact of these sources on overall air quality throughout South Asia.

Environmental context The production and consumption of chlorofluorocarbons (CFCs) is regulated under the Montreal Protocol and its amendments, due to their role in stratospheric ozone depletion. Global atmospheric levels of CFC-11 did not decline as rapidly as expected during 2012–2018, in large part due to emissions from eastern China. In order to further clarify global CFC-11 emissions, this work provides a rare set CFC-11 measurements from understudied countries and sources throughout Asia (1998–2018). Abstract Trichlorofluoromethane (CFC-11) is an ozone-depleting substance whose production and consumption are regulated under the Montreal Protocol. Global atmospheric CFC-11 levels declined less quickly than expected during 2012–2018, largely because of ongoing emissions from eastern Asia. Satellite measurements suggest additional CFC-11 hotspots in the Arabian Peninsula and north India/Nepal. Here we present CFC-11 levels measured in dozens of Asian cities during 1998–2018, including China and Pakistan before the 2010 phaseout of CFC-11, and China, Nepal, Pakistan, Saudi Arabia and South Korea after the phaseout. Surface measurements of CFCs in Nepal, Pakistan and Saudi Arabia are very rare, and these surveys provide important observational constraints from understudied regions. During pre-phaseout campaigns, higher CFC-11 levels were measured in Beijing than Karachi, despite much higher overall volatile organic compound (VOC) levels in Karachi. During post-phaseout campaigns, average CFC-11 levels were higher in inland Shandong Province and Seoul (1.11–1.23× background) than in western Saudi Arabia, Lahore and Kathmandu (1.02–1.11× background), despite higher levels of other VOCs in the latter regions. While China is known to emit excess CFC-11, elevated CFC-11 levels in Seoul, especially during stagnant meteorological conditions, suggest local emissions in 2015–2016. Rough emission estimates suggest that South Korea is likely a relatively minor global source of excess CFC-11. Hotspot CFC-11 levels were measured from a landfill fire in Mecca (average of 1.8× background) and from garbage burning in Nepal (1.5× background). Because garbage burning and open burning in dumps are common practices, further investigation of CFC-11 emissions at dumps and landfills worldwide is encouraged to determine their global impact.

Visitors to the ruins of Ur venturing into the residential area south of the ziggurat and royal cemetery are confronted with a reconstructed “House of Abraham” (fig. 1), named after the city’s most famous putative resident. It is not clear who decided that this particular structure was the ancestral home of the patriarch, but it was certainly not Sir Leonard Woolley, who closed his celebrated excavations here in 1934. While he was convinced that this city was indeed the Ur of the Chaldees of the Bible—a claim that has not gone unchallenged—and even wrote a book postulating that the Old Babylonian houses here shed light on the origins of Yahwistic religion (Woolley 1936), he doubted that archaeology could ever link Abraham to a specific artifact or building. The massive brick structure one sees today was actually erected only two decades ago to promote tourism in anticipation of a papal visit that was delayed until March 2021. It was built on the ruins of half a dozen individual houses that Woolley had excavated in the area he called AH, generally following their ground plans but connecting the units with doorways to create a single edifice many times larger than any private residence of the early second millennium BCE (fig. 2). If the idea of naming this new creation after Abraham was to promote tourism, it has been a success: Among the thousands who visit Ur every spring, some even come to pray in these rooms, ignoring all warnings that the association with the family of Abraham is suspect.Figure 1. Drone image of Ur facing northward, House of Abraham in foreground and ziggurat in the background. Photograph by Berthold Einwag.Figure 2. Woolley plan (in red) on drone image of modern reconstruction of “House of Abraham.” In the reconstruction internal doors were used to join separate houses into one large structure. The geometry does not match precisely. Drone photograph by Berthold Einwag.

ABSTRACTThe Lake Michigan Ozone Study 2017 (LMOS 2017) in May and June 2017 enabled study of transport, emissions, and chemical evolution related to ozone air pollution in the Lake Michigan airshed. Two highly instrumented ground sampling sites were part of a wider sampling strategy of aircraft, shipborne, and ground-based mobile sampling. The Zion, Illinois site (on the coast of Lake Michigan, 67 km north of Chicago) was selected to sample higher NOxair parcels having undergone less photochemical processing. The Sheboygan, Wisconsin site (on the coast of Lake Michigan, 211 km north of Chicago) was selected due to its favorable location for the observation of photochemically aged plumes during ozone episodes involving southerly winds with lake breeze. The study encountered elevated ozone during three multiday periods. Daytime ozone episode concentrations at Zion were 60 ppb for ozone, 3.8 ppb for NOx, 1.2 ppb for nitric acid, and 8.2 μg m-3for fine particulate matter. At Sheboygan daytime, ozone episode concentrations were 60 ppb for ozone, 2.6 ppb for NOx, and 3.0 ppb for NOy. To facilitate informed use of the LMOS 2017 data repository, we here present comprehensive site description, including airmass influences during high ozone periods of the campaign, overview of meteorological and pollutant measurements, analysis of continuous emission monitor data from nearby large point sources, and characterization of local source impacts from vehicle traffic, large point sources, and rail. Consistent with previous field campaigns and the conceptual model of ozone episodes in the area, trajectories from the southwest, south, and lake breeze trajectories (south or southeast) were overrepresented during pollution episodes. Local source impacts from vehicle traffic, large point sources, and rail were assessed and found to represent less than about 15% of typical concentrations measured. Implications for model-observation comparison and design of future field campaigns are discussed.Implications: The Lake Michigan Ozone Study 2017 (LMOS 2017) was conducted along the western shore of Lake Michigan, and involved two well-instrumented coastal ground sites (Zion, IL, and Sheboygan, WI). LMOS 2017 data are publicly available, and this paper provides detailed site characterization and measurement summary to enable informed use of repository data. Minor local source impacts were detected but were largely confined to nighttime conditions of less interest for ozone episode analysis and modeling. The role of these sites in the wider field campaign and their detailed description facilitates future campaign planning, informed data repository use, and model-observation comparison.

Starting from our previous finding of 14 known drugs as inhibitors of the main protease (Mpro) of SARS-CoV-2, the virus responsible for COVID-19, we have redesigned the weak hit perampanel to yield multiple noncovalent, nonpeptidic inhibitors with ca. 20 nM IC50values in a kinetic assay. Free-energy perturbation (FEP) calculations for Mpro-ligand complexes provided valuable guidance on beneficial modifications that rapidly delivered the potent analogues. The design efforts were confirmed and augmented by determination of high-resolution X-ray crystal structures for five analogues bound to Mpro. Results of cell-based antiviral assays further demonstrated the potential of the compounds for treatment of COVID-19. In addition to the possible therapeutic significance, the work clearly demonstrates the power of computational chemistry for drug discovery, especially FEP-guided lead optimization.

Extant research shows veterinarians face increasing challenges in discussing nutrition with clients despite receiving professional nutrition education in the veterinary medical curriculum. This article’s aim is to elicit student veterinarians’ baseline nutrition-related perceptions and nutrition information-seeking behaviors at the time of entering veterinary school. Participants were newly enrolled veterinary students at the Ontario Veterinary College (n= 120). Focus group discussions (n= 19) informed the design of an online questionnaire capturing students’ demographics and perceptions of their own and their pets’ nutrition. Students reported being influenced by individual factors (e.g., time), social networks (e.g., family), and surrounding environment (e.g., cost, contradictory media messages). Overall, 58% of students considered themselves knowledgeable about pet nutrition when commencing veterinary school, with 71% prioritizing their pets’ diets as much as their own. Students’ confidence in finding pet nutrition information was correlated with perceived accessibility (r= .76, p= .001) and perceived quantity of information available on pet nutrition (r= .83, p= .001), but not quality of information (r= .13, p= .03). In general, students relied on and trusted veterinarians for nutrition advice. However, 94% of students mistrusted pet food companies’ motivations. Our data support that students entering veterinary school have their own perceptions on pet nutrition that impact nutrition education, suggesting this as an important consideration in the design and delivery of a veterinary nutrition curriculum. Veterinary medical faculty should be encouraged to discuss baseline nutrition information and address any misconceptions to prepare students for future consultations with clients.

Background: Blood tests play a vital role in veterinary medicine, as they enable veterinarians to make decisions about their patients’ medical care and provide opportunities to engage clients in veterinary care. The objective of this study was to explore perspectives of veterinary clients and veterinarians on current reporting practices for blood tests ordered in companion animal practice. The type of information communicated and client information seeking behaviours were examined. Methods: Two online surveys were distributed using snowball sampling: one targeting veterinary clients and one targeting veterinarians. Results: In total, 529 veterinary client and 416 veterinarian surveys were included in analyses. Significant differences were found between what blood test information veterinarian respondents felt they provided clients and what client respondents perceived they received with regard to their pet's blood tests. Almost 60% of clients somewhat or strongly agreed that they search the Internet if they do not understand why a test was ordered or what the results mean. Half of clients reported that they never receive a written report of their pet's blood work, 81% of whom were interested in receiving a copy. Conclusion: Results of this research demonstrate opportunities to improve veterinarians’ and clients’ communication about blood tests.

This review of the literature was conducted to define avoidant restrictive food intake disorder (ARFID) and provide the current evidence-based treatment modalities and implications for Nurse Practitioners. A specific case is used to illustrate the daily struggles of a pediatric patient with ARFID that include bullying, self-doubt, and anxiety related to eating. There is a need for increased awareness of the disorder to increase identification of the disorder, enhance the research on treatment modalities for the disorder, and most importantly, to increase the quality of life for those with the disorder and their family members.

Ice nucleating particles (INPs) influence weather and climate by their effect on cloud phase state. Fatty alcohols present within aerosol particles confer a potentially important source of ice nucleation activity to sea spray aerosol produced in oceanic regions. However, their interactions with other aerosol components and the influence on freezing were previously largely unknown. Here, we report quantitative measurements of fatty alcohols in model sea spray aerosol and examine the relationships between the composition and structure of the surfactants and subphase in the context of these measurements. Deposited mixtures of surfactants retain the ability to nucleate ice, even in fatty acid-dominant compositions. Strong refreezing effects are also observed, where previously frozen water–surfactant samples nucleate more efficiently. Structural sources of refreezing behavior are identified as either kinetically trapped film states or three-dimensional (3D) solid surfactant particles. Salt effects are especially important for surfactant INPs, where high salt concentrations suppress freezing. A simple water uptake model suggests that surfactant-containing aerosol requires either very low salt content or kinetic trapping as solid particles to act as INPs in the atmosphere. These types of INPs could be identified through comparison of different INP instrument responses.

Background: Americans spend most of their time indoors. Indoor particulate matter (PM) 2.5 µm and smaller (PM2.5) concentrations often exceed ambient concentrations. Therefore, we tested whether the use of an air purifying device (electrostatic precipitator, ESP) could reduce PM2.5in homes of smokers with and without respiratory exacerbations, compared with baseline. Methods: We assessed PM2.5concentrations in homes of subjects with and without a recent (≤3 years) history of respiratory exacerbation. We compared PM2.5concentrations during 1 month of ESP use with those during 1 month without ESP use. Results: Our study included 19 subjects (53–80 years old), nine with a history of respiratory exacerbation. Geometric mean (GM) PM2.5and median GM daily peak PM2.5were significantly lower during ESP deployment compared with the equivalent time-period without the ESP (GSD = 0.50 and 0.37 µg/m3, respectively, p&lt; 0.001). PM2.5in homes of respiratory exacerbators tended (p&lt; 0.14) to be higher than PM2.5in homes of those without a history of respiratory exacerbation. Conclusions: Subjects with a history of respiratory exacerbation tended to have higher mean, median, and mean peak PM2.5concentrations compared with homes of subjects without a history of exacerbations. The ESP intervention reduced in-home PM2.5concentrations, demonstrating its utility in reducing indoor exposures. Novelty of study: Our work characterizes PM air pollution concentrations in homes of study subjects with and without respiratory exacerbations. We demonstrate that PM concentrations tend to be higher in homes of participants with respiratory exacerbations, and that the use of an inexpensive air purifier resulted in significantly lower daily average PM concentrations than when the purifier was not present. Our results provide a helpful intervention strategy for purifying indoor air and may be useful for susceptible populations.

Increasing air pollution in South Asia has serious consequences for air quality and human/ecosystem health within the region. South Asia, including India and Nepal, suffers from severe air pollution, including high concentrations of aerosols, as well as gaseous pollutants. One of the often-neglected sources contributing to the regional air pollution is garbage burning. It is mostly related to numerous yet small, open, uncontrolled fires burning diverse fuels, making it difficult to quantify activity and emissions. In this study, we attempted to quantify the total emissions due to garbage burning and its contribution to regional air quality, using new observational data, a new inventory, and a regional chemical transport model. We implemented the newly available emission factors (EFs) from a recent field campaign, Nepal Ambient Monitoring and Source Testing Experiment (NAMaSTE), which took place in April 2015. Using a chemical transport model—Weather Research and Forecasting model coupled with Chemistry version 3.5 (WRF-Chem)—and three emission scenarios, we assessed the impact of open garbage burning emissions on regional air quality. Our results show that garbage burning emissions could increase PM2.5concentrations by nearly 30% in India and Nepal, and result in ∼300 000 premature deaths from chronic obstructive pulmonary disease in the two countries.

We demonstrate a facile approach for the synthesis of gem-disubstituted cyclooctanoids, a motif found in several biologically active compounds. Appropriately substituted 1-alkenyl-5-pentyn-1-ols bearing gem-dialkyl substituents at either the C2, C3, or C4 position serve as useful precursors to a number of cyclooct-4-enone derivatives via a tandem, microwave-assisted oxyanionic 6-exo-digcyclization/Claisen rearrangement reaction. gem-Dialkyl activation is necessary for these reactions to occur, as unactivated 1-alkenyl-5-pentyn-1-ols fail to undergo 6-exo-digcyclization under the conditions employed. Further application of the methodology to the corresponding gem-dialkoxy system was also explored to facilitate access to more complex carbocycles.

Analogues of the conformationally dynamic Claritin (loratadine) and Clarinex (desloratadine) scaffolds have been enantio- and chemoselectively N-oxidized using an aspartic acid containing peptide catalyst to afford stable, helically chiral products in up to >99:1 er. The conformational dynamics and enantiomeric stability of the N-oxide products have been investigated experimentally and computationally with the aid of crystallographic data. Furthermore, biological assays show that rigidifying the core structure of loratadine and related analogues through N-oxidation affects antihistamine activity in an enantiomer-dependent fashion. Computational docking studies illustrate the observed activity differences.

We describe the summative assessment component within a K–12 assessment program and our development of a validity argument to support its claims with respect to intended uses and interpretations. First, we describe the Winsight® assessment program theory of action, a logic model elucidating mechanisms for how use of the assessment components can lead to improved student learning in mathematics and English language arts (ELA) and defining the roles of key groups of stakeholders. We explain our process of developing the validity argument that enumerates sources of validity evidence supporting the Winsight summative assessment claims drawn from the theory of action. We examine candidate structures for the argument, describe the steps in which we unpacked stakeholder‐level claims and defined subclaims to operationalize components, and discuss types and sources of validity evidence to meet the goals of professional and federal guidelines. Finally, we discuss the research agenda and operational analyses that will provide this validity evidence. Report Number: ETS RR–19‐26