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DOE OSTI2019

Inorganic Element Concentrations in Passerine Eggs Collected at Technical Areas 36, 39, and 16 at Los Alamos National Laboratory

In 2018, nonviable avian eggs were opportunistically collected at Los Alamos National Laboratory near open detonation sites at Technical Area (TA) 36 and TA-39 and near the TA-16 burning grounds and were evaluated for inorganic elements (mostly metals). A total of eight western bluebird Sialia mexicana ) and ash-throated flycatcher ( Myiarchus cinerascens ) egg samples were collected among the three locations of interest. Due to the small sample size, statistical comparisons could not be made. However, concentrations of inorganic elements observed in this study were compared with the upper-level bounds of background concentrations (mean + three standard deviations = 99% confidence interval; regional statistical reference level [RSRL]). Several inorganic elements were not detected in avian eggs and the majority of inorganic elements detected were below the RSRL. The few elements that exceeded the RSRL were below the lowest observable adverse effect level (LOAEL), when available. These data suggest that inorganic element concentrations in eggs observed here are not of ecological concern. As these data are preliminary, more data are needed to make a robust assessment, including additional background samples.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2019

An interval of high salinity in ancient Gale crater lake on Mars

Precipitated minerals, including salts, are primary tracers of atmospheric conditions and water chemistry in lake basins. Ongoing in situ exploration by the Curiosity rover of Hesperian (around 3.3–3.7 Gyr old) sedimentary rocks within Gale crater on Mars has revealed clay-bearing fluvio-lacustrine deposits with sporadic occurrences of sulfate minerals, primarily as late-stage diagenetic veins and concretions. In this work, we report bulk enrichments, disseminated in the bedrock, of 30–50 wt% calcium sulfate intermittently over about 150 m of stratigraphy, and of 26–36 wt% hydrated magnesium sulfate within a thinner section of strata. We use geochemical analysis, primarily from the ChemCam laser-induced breakdown spectrometer, combined with results from other rover instruments, to characterize the enrichments and their lithology. The deposits are consistent with early diagenetic, pre-compaction salt precipitation from brines concentrated by evaporation, including magnesium sulfate-rich brines from extreme evaporative concentration. This saline interval represents a substantial hydrological perturbation of the lake basin, which may reflect variations in Mars’ obliquity and orbital parameters. Our findings support stepwise changes in Martian climate during the Hesperian, leading to more arid and sulfate-dominated environments as previously inferred from orbital observations.

58 GEOSCIENCES↗
DOE OSTI2022

Nonsynonymous amino acid changes in the α-chain of complement component 5 influence longitudinal susceptibility to Plasmodium falciparum infections and severe malarial anemia in kenyan children

Background: Severe malarial anemia (SMA; Hb < 5.0 g/dl) is a leading cause of childhood morbidity and mortality in holoendemic Plasmodium falciparum transmission regions such as western Kenya. Methods: We investigated the relationship between two novel complement component 5 (C5) missense mutations [rs17216529:C>T, p(Val145Ile) and rs17610:C>T, p(Ser1310Asn)] and longitudinal outcomes of malaria in a cohort of Kenyan children (under 60 mos, n = 1,546). Molecular modeling was used to investigate the impact of the amino acid transitions on the C5 protein structure. Results: Prediction of the wild-type and mutant C5 protein structures did not reveal major changes to the overall structure. However, based on the position of the variants, subtle differences could impact on the stability of C5b. The influence of the C5 genotypes/haplotypes on the number of malaria and SMA episodes over 36 months was determined by Poisson regression modeling. Genotypic analyses revealed that inheritance of the homozygous mutant (TT) for rs17216529:C>T enhanced the risk for both malaria (incidence rate ratio, IRR = 1.144, 95%CI: 1.059–1.236, p = 0.001) and SMA (IRR = 1.627, 95%CI: 1.201–2.204, p = 0.002). In the haplotypic model, carriers of TC had increased risk of malaria (IRR = 1.068, 95%CI: 1.017–1.122, p = 0.009), while carriers of both wild-type alleles (CC) were protected against SMA (IRR = 0.679, 95%CI: 0.542–0.850, p = 0.001). Conclusion: Collectively, these findings show that the selected C5 missense mutations influence the longitudinal risk of malaria and SMA in immune-naïve children exposed to holoendemic P. falciparum transmission through a mechanism that remains to be defined.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Response of the Quasi–Biennial Oscillation to a warming climate in global climate models

We compare the response of the Quasi–Biennial Oscillation (QBO) to a warming climate in eleven atmosphere general circulation models that performed time–slice simulations for present–day, doubled, and quadrupled CO 2 climates. No consistency was found among the models for the QBO period response, with the period decreasing by 8 months in some models and lengthening by up to 13 months in others in the doubled CO 2 simulations. In the quadrupled CO 2 simulations, a reduction in QBO period of 14 months was found in some models, whereas in several others the tropical oscillation no longer resembled the present–day QBO, although it could still be identified in the deseasonalized zonal mean zonal wind timeseries. In contrast, all the models projected a decrease in the QBO amplitude in a warmer climate with the largest relative decrease near 60 hPa. In simulations with doubled and quadrupled CO 2 , the multi–model mean QBO amplitudes decreased by 36 and 51%, respectively. Across the models the differences in the QBO period response were most strongly related to how the gravity wave momentum flux entering the stratosphere and tropical vertical residual velocity responded to the increases in CO 2 amounts. Likewise it was found that the robust decrease in QBO amplitudes was correlated across the models to changes in vertical residual velocity, parametrized gravity wave momentum fluxes, and to some degree the resolved upward wave flux. Here, we argue that uncertainty in the representation of the parameterized gravity waves is the most likely cause of the spread among the eleven models in the QBO's response to climate change.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

Los Alamos National Laboratory Floodplain Assessment for Fire Risk Mitigations at the Lower Slobbovia Testing Site in (TA-36)

The National Nuclear Security Administration (NNSA), a semi-autonomous agency within the U.S. Department of Energy (DOE), is proposing to take fire pre-suppression actions at Los Alamos National Laboratory (LANL) Technical Area (TA) 36. Constructing a fire break and a fuel break surrounding the Lower Slobbovia explosives testing site in addition to the current vegetation mowing practices would establish a safety perimeter to help prevent fires from spreading away from the firing point. NNSA has prepared this floodplain assessment in accordance with 10 Code of Federal Regulations (CFR) Part 1022 Compliance with Floodplain and Wetland Environmental Review Requirements (10 CFR 1022), which was promulgated to implement DOE requirements under Executive Order 11988 Floodplain Management (EO 1977). A floodplain is defined in 10 CFR 1022 as “the lowlands adjoining inland and coastal waters and relatively flat areas and flood prone areas of offshore islands,” and a base floodplain as “the 100-year floodplain, that is, a floodplain with a 1.0 percent chance of flooding in any given year (CFR 2003).” This floodplain assessment evaluates potential impacts to floodplain values and functions from implementation of the proposed action, identifies alternatives to the Proposed Action, and allows for meaningful public comment.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2020

Halogenation as a tool to tune antimicrobial activity of peptoids

Antimicrobial peptides have attracted considerable interest as potential new class of antibiotics against multi-drug resistant bacteria. However, their therapeutic potential is limited, in part due to susceptibility towards enzymatic degradation and low bioavailability. Peptoids (oligomers of N-substituted glycines) demonstrate proteolytic stability and better bioavailability than corresponding peptides while in many cases retaining antibacterial activity. In this study, we synthesized a library of 36 peptoids containing fluorine, chlorine, bromine and iodine atoms, which vary by length and level of halogen substitution in position 4 of the phenyl rings. As we observed a clear correlation between halogenation of an inactive model peptoid and its increased antimicrobial activity, we designed chlorinated and brominated analogues of a known peptoid and its shorter counterpart. Short brominated analogues displayed up to 32-fold increase of the activity against S. aureus and 16- to 64-fold against E. coli and P. aeruginosa alongside reduced cytotoxicity. The biological effect of halogens seems to be linked to the relative hydrophobicity and self-assembly properties of the compounds. By small angle X-ray scattering (SAXS) we have demontrated how the self-assembled structures are dependent on the size of the halogen, degree of substitution and length of the peptoid, and correlated these features to their activity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Partitioning net carbon dioxide fluxes into photosynthesis and respiration using neural networks

The eddy covariance (EC) technique is used to measure the net ecosystem exchange (NEE) of CO 2 between ecosystems and the atmosphere, offering a unique opportunity to study ecosystem responses to climate change. NEE is the difference between the total CO 2 release due to all respiration processes (RECO), and the gross carbon uptake by photosynthesis (GPP). These two gross CO 2 fluxes are derived from EC measurements by applying partitioning methods that rely on physiologically based functional relationships with a limited number of environmental drivers. However, the partitioning methods applied in the global FLUXNET network of EC observations do not account for the multiple co-acting factors that modulate GPP and RECO flux dynamics. To overcome this limitation, we developed a hybrid data-driven approach based on combined neural networks (NN C-part ). NN C-part incorporates process knowledge by introducing a photosynthetic response based on the light-use efficiency (LUE) concept, and uses a comprehensive dataset of soil and micrometeorological variables as fluxes drivers. We applied the method to 36 sites from the FLUXNET2015 dataset and found a high consistency in the results with those derived from other standard partitioning methods for both GPP (R 2 > .94) and RECO (R 2 > .8). High consistency was also found for (a) the diurnal and seasonal patterns of fluxes and (b) the ecosystem functional responses. NNC-part performed more realistic than the traditional methods for predicting additional patterns of gross CO 2 fluxes, such as: (a) the GPP response to VPD, (b) direct effects of air temperature on GPP dynamics, (c) hysteresis in the diel cycle of gross CO 2 fluxes, (d) the sensitivity of LUE to the diffuse to direct radiation ratio, and (e) the post rain respiration pulse after a long dry period. In conclusion, NN C-part is a valid data-driven approach to provide GPP and RECO estimates and complementary to the existing partitioning methods.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2019

Discovery of Geographically Robust Hybrid Poplar Clones

Hybrid poplar clonal growth in the states (regions) of Minnesota (MN), Indiana (IN), Michigan (MI), and New York (NY) USA was analyzed to discover 10 geographically robust (geo-robust) clones, all P. deltoides x P. nigra (D x N) hybrids previously tested and screened in MN, that were broadly adapted across latitudinal and longitudinal ranges of 9 and 20 degrees, respectively. The clonal effect for growth explained 25 to 36 % of the total variance, 2.5–4.1 times the clone x site interaction. Clone explained 24 to 46 % of total variation in canker occurrence on two sites. Genetic gain in growth was calculated relative to commercial check clones. Genetic gain in growth of geo-robust clones exceeded that of random clones by 24 to 44 %. Geo-robust clones and the best clones on each site were not significantly different on the MN sites, but best clones outperformed geo-robust clones on the other sites by 10 to 39 % genetic gain. Geo-robust clones grew faster than commercial check clones on all but the MI site. The reduction in genetic gain for growth due to using broadly adapted clones relative to the best clones has to be compared to the additional costs and benefits of multiple breeding zones.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Unveiling the mechanism of lithium-mediated nitrogen reduction via operando X-ray scattering in a flow cell with hydrogen oxidation

The lithium-mediated nitrogen reduction reaction (Li-NRR) is currently the most promising strategy for electrochemical ammonia synthesis. In this study, we present an operando grazing incidence wide angle X-ray scattering (GI WAXS) investigation using an improved electrochemical flow cell that enables hydrogen oxidation at the anode and thereby eliminates the need of a sacrificial proton donor. The improved cell design also increases nitrogen availability and mass transport, achieving ammonia faradaic efficiencies (FEs) up to 36%. This setup allows direct analysis of reaction intermediates and the solid electrolyte interphase (SEI) using state-of-the-art diglyme-based electrolytes. We identify lithium amide (LiNH2) as the only stable, crystalline intermediate, providing direct insight into the Li-NRR mechanism. Notably, in diglyme-based electrolytes, the SEI composition differs significantly from that in tetrahydrofuran-based systems, with reduced LiF content and the formation of previously unreported crystalline diglyme–lithium salt complexes. These species likely influence ammonia selectivity and long-term stability. Our findings highlight how the electrolyte composition and cell architecture govern Li-NRR selectivity and efficiency, offering a foundation for the rational design of next-generation SEI layers and solid electrolytes to enable scalable electrochemical ammonia synthesis.

Deissler, Niklas H. [Technical Univ. of Denmark, L↗
DOE OSTI2023

Striatal dopamine synthesis and cognitive flexibility differ between hormonal contraceptive users and nonusers

In rodents and nonhuman primates, sex hormones are powerful modulators of dopamine (DA) neurotransmission. Yet less is known about hormonal regulation of the DA system in the human brain. Using positron emission tomography (PET), we address this gap by comparing hormonal contraceptive users and nonusers across multiple aspects of DA function: DA synthesis capacity via the PET radioligand 6-[ 18 F]fluoro-m-tyrosine ([ 18 F]FMT), baseline D2/3 receptor binding potential using [ 11 C]raclopride, and DA release using methylphenidate-paired [ 11 C]raclopride. Participants consisted of 36 healthy women (n = 15 hormonal contraceptive users; n = 21 naturally cycling/non users of hormonal contraception), and men (n = 20) as a comparison group. A behavioral index of cognitive flexibility was assessed prior to PET imaging. Hormonal contraceptive users exhibited greater DA synthesis capacity than NC participants, particularly in dorsal caudate, and greater cognitive flexibility. Furthermore, across individuals, the magnitude of striatal DA synthesis capacity was associated with cognitive flexibility. No group differences were observed in D2/3 receptor binding or DA release. Analyses by sex alone may obscure underlying differences in DA synthesis tied to women’s hormone status. Hormonal contraception (in the form of pill, shot, implant, ring, or intrauterine device) is used by ~400 million women worldwide, yet few studies have examined whether chronic hormonal manipulations impact basic properties of the DA system. Findings from this study begin to address this critical gap in women’s health.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Core line spread function calibration of the X-ray Imaging and Spectroscopy Mission Resolve X-ray calorimeter spectrometer

The Resolve X-ray imaging spectrometer onboard the X-ray Imaging and Spectroscopy Mission consists of a 36 pixel array of high-resolution X-ray calorimeters each with ∼ 5 eV full-width-at-half-maximum (FWHM) spectral resolution in the 0.3 to 12 keV band. The response to monochromatic X-rays (line spread function, LSF) is composed of a narrow Gaussian core and weak extended components caused by energy loss during thermalization. We report on the characterization of the Gaussian core LSF in an extensive ground calibration campaign. We also discuss the characterization of on-orbit resolution, which shows slightly higher FWHM than that obtained on the ground.

Astronomy and AstroPhysics↗
DOE OSTI2021

Population genomics provides insights into the genetic basis of adaptive evolution in the mushroom-forming fungus Lentinula edodes

Introduction: Mushroom-forming fungi comprise diverse species that develop complex multicellular structures. In cultivated species, both ecological adaptation and artificial selection have driven genome evolution. However, little is known about the connections among genotype, phenotype and adaptation in mushroom-forming fungi. Objectives: This study aimed to (1) uncover the population structure and demographic history of Lentinula edodes, (2) dissect the genetic basis of adaptive evolution in L. edodes, and (3) determine if genes related to fruiting body development are involved in adaptive evolution. Methods: We analyzed genomes and fruiting body-related traits (FBRTs) in 133 L. edodes strains and conducted RNA-seq analysis of fruiting body development in the YS69 strain. Combined methods of genomic scan for divergence, genome-wide association studies (GWAS), and RNA-seq were used to dissect the genetic basis of adaptive evolution. Results: We detected three distinct subgroups of L. edodes via single nucleotide polymorphisms, which showed robust phenotypic and temperature response differentiation and correlation with geographical distribution. Demographic history inference suggests that the subgroups diverged 36,871 generations ago. Moreover, L. edodes cultivars in China may have originated from the vicinity of Northeast China. A total of 942 genes were found to be related to genetic divergence by genomic scan, and 719 genes were identified to be candidates underlying FBRTs by GWAS. Integrating results of genomic scan and GWAS, 80 genes were detected to be related to phenotypic differentiation. A total of 364 genes related to fruiting body development were involved in genetic divergence and phenotypic differentiation. Conclusion: Adaptation to the local environment, especially temperature, triggered genetic divergence and phenotypic differentiation of L. edodes. A general model for genetic divergence and phenotypic differentiation during adaptive evolution in L. edodes, which involves in signal perception and transduction, transcriptional regulation, and fruiting body morphogenesis, was also integrated here.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Evidence of co-exposure with Brucella spp, Coxiella burnetii , and Rift Valley fever virus among various species of wildlife in Kenya

Co-infection, especially with pathogens of dissimilar genetic makeup, may result in a more devastating impact on the host. Investigations on co-infection with neglected zoonotic pathogens in wildlife are necessary to inform appropriate prevention and control strategies to reduce disease burden in wildlife and the potential transmission of these pathogens between wildlife, livestock and humans. This study assessed co-exposure of various Kenyan wildflife species with Brucella spp, Coxiella burnetii and Rift Valley fever virus (RVFV). A total of 363 sera from 16 different wildlife species, most of them (92.6%) herbivores, were analysed by Enzyme-linked immunosorbent assay (ELISA) for IgG antibodies against Brucella spp, C. burnetii and RVFV. Further, 280 of these were tested by PCR to identify Brucella species. Of the 16 wildlife species tested, 15 (93.8%) were seropositive for at least one of the pathogens. Mean seropositivities were 18.9% (95% CI: 15.0–23.3) for RVFV, 13.7% (95% CI: 10.3–17.7) for Brucella spp and 9.1% (95% CI: 6.3–12.5) for C. burnetii. Buffaloes (n = 269) had higher seropositivity for Brucella spp. (17.1%, 95% CI: 13.0–21.7%) and RVFV (23.4%, 95% CI: 18.6–28.6%), while giraffes (n = 36) had the highest seropositivity for C. burnetii (44.4%, 95% CI: 27.9–61.9%). Importantly, 23 of the 93 (24.7%) animals positive for at least one pathogen were co-exposed, with 25.4% (18/71) of the positive buffaloes positive for brucellosis and RVFV. On molecular analysis, Brucella DNA was detected in 46 (19.5%, CI: 14.9–24.7) samples, with 4 (8.6%, 95% CI: 2.2–15.8) being identified as B. melitensis. The Fisher’s Exact test indicated that seropositivity varied significantly within the different animal families, with Brucella (p = 0.013), C. burnetii (p = <0.001) and RVFV (p = 0.007). Location was also significantly associated (p = <0.001) with Brucella spp. and C. burnetii seropositivities. Of ~20% of Kenyan wildlife that are seropositive for Brucella spp, C. burnetii and RVFV, almost 25% indicate co-infections with the three pathogens, particularly with Brucella spp and RVFV.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Population genomics of the pathogenic yeast Candida tropicalis identifies hybrid isolates in environmental samples

Candida tropicalis is a human pathogen that primarily infects the immunocompromised. Whereas the genome of one isolate, C. tropicalis MYA-3404, was originally sequenced in 2009, there have been no large-scale, multi-isolate studies of the genetic and phenotypic diversity of this species. Here, we used whole genome sequencing and phenotyping to characterize 77 isolates of C. tropicalis from clinical and environmental sources from a variety of locations. We show that most C. tropicalis isolates are diploids with approximately 2–6 heterozygous variants per kilobase. The genomes are relatively stable, with few aneuploidies. However, we identified one highly homozygous isolate and six isolates of C. tropicalis with much higher heterozygosity levels ranging from 36–49 heterozygous variants per kilobase. Our analyses show that the heterozygous isolates represent two different hybrid lineages, where the hybrids share one parent (A) with most other C. tropicalis isolates, but the second parent (B or C) differs by at least 4% at the genome level. Four of the sequenced isolates descend from an AB hybridization, and two from an AC hybridization. The hybrids are MTLa/α heterozygotes. Hybridization, or mating, between different parents is therefore common in the evolutionary history of C. tropicalis. The new hybrids were predominantly found in environmental niches, including from soil. Hybridization is therefore unlikely to be associated with virulence. In addition, we used genotype-phenotype correlation and CRISPR-Cas9 editing to identify a genome variant that results in the inability of one isolate to utilize certain branched-chain amino acids as a sole nitrogen source.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Climate vs Energy Security: Quantifying the Trade-offs of BECCS Deployment and Overcoming Opportunity Costs on Set-Aside Land

Bioenergy with carbon capture and storage (BECCS) sits at the nexus of the climate and energy security. We evaluated trade-offs between scenarios that support climate stabilization (negative emissions and net climate benefit) or energy security (ethanol production). Our spatially explicit model indicates that the foregone climate benefit from abandoned cropland (opportunity cost) increased carbon emissions per unit of energy produced by 14–36%, making geologic carbon capture and storage necessary to achieve negative emissions from any given energy crop. The toll of opportunity costs on the climate benefit of BECCS from set-aside land was offset through the spatial allocation of crops based on their individual biophysical constraints. Dedicated energy crops consistently outperformed mixed grasslands. We estimate that BECCS allocation to land enrolled in the Conservation Reserve Program (CRP) could capture up to 9 Tg C year –1 from the atmosphere, deliver up to 16 Tg CE year –1 in emissions savings, and meet up to 10% of the US energy statutory targets, but contributions varied substantially as the priority shifted from climate stabilization to energy provision. Furthermore, our results indicate a significant potential to integrate energy security targets into sustainable pathways to climate stabilization but underpin the trade-offs of divergent policy-driven agendas.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗
DOE OSTI2019

Therapeutic effects of moxibustion simultaneously targeting Nrf2 and NF-κB in diabetic peripheral neuropathy

Moxibustion is the main alternative medicine treatment that has been beneficial to diabetic peripheral neuropathy (DPN), a common complication secondary to diabetic microvascular injury. However, the underlying protective mechanism of moxibustion against neuroinflammation remains unclear. We hypothesized that moxibustion treats DPN by regulating the balance of nuclear factor-2 erythroid-related factor-2 (Nrf2)-nuclear factor-kappa light chain enhancer of B cells (NF-кB). In vivo, diabetes was induced in rats by injecting streptozotocin (STZ; 60 mg/kg; i.p.). Moxibustion was then applied to “Zusanli” (ST 36), “Guanyuan” (BL 26), and “Yishu” (EX-B 3) acupuncture points. Nerve conduction was detected. Serum interleukin (IL)-1β, IL-6, and IL-8 levels were determined through enzyme-linked immunosorbent assay. NF-κB and Nrf2 proteins were examined through immunoblot analysis. The mRNA of NF-κB and Nrf2 was evaluated through RT-PCR. We found that the conduction velocity and amplitude of the action potentials of sciatic nerve conduction were reduced in the DPN model group but were rescued by moxibustion treatment. Moxibustion also improved the effect of DPN on other parameters, including ultrastructural changes, NF-κB and Nrf2 expression in the sciatic nerve, and serum IL-1β, IL-6, and IL-8 levels. Our data suggested that moxibustion may alleviate neuroinflammation by inhibiting NF-κB and by activating Nrf2. Moxibustion may also provide therapeutic effects for patients with DPN by simultaneously targeting Nrf2 and NF-κB.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

HIV drug resistance during antiretroviral therapy scale-up in Uganda, 2012–19: a population-based, longitudinal study

Background With scale-up of antiretroviral therapy (ART) in sub-Saharan Africa, increasing pretreatment HIV drug resistance has been reported; however, the broader effect of ART expansion on population-level resistance patterns remains insufficiently quantified. We aimed to estimate the longitudinal prevalence of drug resistance and resistance-conferring mutations. Methods This study used data collected as part of the Rakai Community Cohort Study (RCCS), an open population-based census and cohort study conducted in southern Uganda. At each survey round, residents aged 15–49 years are invited to participate and receive a structured questionnaire that obtains sociodemographic, behavioural, and health information, including self-reported past and current ART use. Voluntary HIV testing is conducted using a rapid test algorithm and a venous blood sample. People with HIV provide samples for viral load quantification and deep sequencing. We analysed RCCS survey, HIV viral load, and deep sequencing (which was used to predict resistance) data from five survey rounds. The key outcomes were the population prevalence of viraemic people with HIV with non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI), protease inhibitor, or multiclass resistance among all participants (regardless of HIV serostatus) in the 2015 and 2017 surveys. Prevalence of class-specific resistance and resistance-conferring substitutions were estimated using robust log-Poisson regression. Findings Between Aug 10, 2011, and Nov 4, 2020, there were 43 361 participants in the RCCS and 7923 (18·27%) people with HIV. Over five survey rounds, 93 622 participant visits occurred, among which 17 460 (18·65%) were from people with HIV. Over the analysis period, the median age of study participants remained similar (28 years [22–35] in 2012 and 29 years [21–38] in 2019). Sufficient data were available to reliably genotype 4072 (90·03%) of 4523 participant visits from 3407 people with HIV for at least one drug. Overall population prevalence of resistance contributed by viraemic pretreatment people with HIV decreased between 2012 and 2017 from 0·56% (95% CI 0·42–0·75) to 0·25% (0·18–0·33) for NNRTI and from 0·24% (0·15–0·37) to 0·05% (0·02–0·10) for NRTI (prevalence ratio 0·44 [0·29–0·68] for NNRTI and 0·21 [0·09–0·47] for NRTI). Between 2012 and 2017, NNRTI resistance among viraemic pretreatment people with HIV increased from 4·86% (3·69–6·42) to 9·61% (7·27–12·7; prevalence ratio 1·98 [1·34–2·91]). The prevalence of NNRTI and NRTI resistance was substantially higher among viraemic treatment-experienced people with HIV (51·49% [46·24–57·34] for NNRTI and 36·46% [30·06–44·22] for NRTI in 2017) than among pretreatment people with HIV. NNRTI and NRTI resistance was predominantly attributable to rtK103N and rtM184V. inT97A was observed at a similar prevalence among viraemic treatment-experienced (9·96% [6·41–15·48]) and viraemic pretreatment (10·56% [8·01–13·93]) people with HIV; no major dolutegravir resistance mutations were observed. Interpretation Despite rising NNRTI resistance among pretreatment people with HIV, overall population prevalence of pretreatment HIV drug-resistant viraemia decreased due to increasing ART uptake and viral suppression. This finding underscores the crucial role of achieving and maintaining high ART coverage in reducing transmission of drug-resistant HIV. The high prevalence of mutations conferring resistance to components of first-line ART regimens among viraemic people with HIV is potentially concerning. Funding National Institutes of Health, Johns Hopkins University Center for AIDS Research, Bill & Melinda Gates Foundation, and the US Centers for Disease Control and Prevention.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Radiation hardness characterization of LKH-5 scintillating glass

Radiation hardness is an important property to examine in scintillators to help determine their expected lifetime in application cases where significant radiation dose is expected. Industrial imaging systems using 9 MV linear accelerators for x-ray radiography are one such application where significant radiation doses are expected to the scintillators used. Cadmium tungstate scintillators (CWO) and Thallium doped Cesium Iodide scintillators (CsI(Tl)) are used in some high energy cargo x-ray radiography systems. However, CWO has a high manufacturing cost for adequately uniform crystals and CsI(Tl) does not have sufficient radiation hardness. LKH-5 glass is being investigated as a potential low cost replacement for CWO and CsI(Tl). In this experiment 36 samples of a terbium doped silicate glass called LKH-5 were irradiated at doses up to 5 MRad using a 9 MV linear accelerator, and the change in their transmission properties was observed. Additionally, the glass was discovered to be a radiation hard glass due to the relatively small change in the transmission of the glass: less than 3% per cm at its emission peak of 550 nm and 5 MRad. This is similar to CWO which has a reported reduction in transmitted light of 2% per cm at 5 MRad and the emission peak of 475 nm and better than CsI(Tl) which is reported to have a reduction in transmitted light of 5% per cm at the emission peak of 550 nm and 4.2 MRad dose. Furthermore, an annealing procedure is described that returned the transmission of the glass to pre-irradiation values.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗