Impact Of Low-Frequency HIV-1 Drug Resistance Mutations On Antiretroviral Therapy Outcomes.

BACKGROUND: The association between low-frequency HIV-1 drug resistance mutations (DRMs) and treatment failure (TF) is controversial. We explore this association using NGS methods that accurately sample low-frequency DRMs. METHODS: We enrolled women with HIV-1 in Malawi who were either ART naïve (A), had ART failure (B), or had discontinued ART (C). At entry, A and C began an NNRTI-based regimen and B started a PI-based regimen. We used Primer ID MiSeq to identify regimen-relevant DRMs in entry and TF plasma samples, and a Cox proportional hazards model to calculate hazard ratios (HRs) for entry DRMs. Low-frequency DRMs were defined as ≤ 20%. RESULTS: We sequenced 360 participants. Cohort B and C participants were more likely to have TF than Cohort A participants. The presence of K103N at entry significantly increased TF risk among A and C participants at both high and low frequency, with HR of 3.12 [1.58-6.18, 95% CI] and 2.38 [1.00-5.67, 95% CI] respectively. At TF, 45% of participants showed selection of DRMs while in the remaining participants there was an apparent lack of selective pressure from ART. CONCLUSIONS: Using accurate NGS for DRM detection may benefit an additional 10% of the patients by identifying low-frequency K103N mutations.

Use of Next-Generation Sequencing in a State-Wide Strategy of HIV-1 Surveillance: Impact of the SARS-COV-2 Pandemic on HIV-1 Diagnosis and Transmission.

BACKGROUND: The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic posed an unpreceded threat to the management of other pandemics such as human immunodeficiency virus-1 (HIV-1) in the United States. The full impact of the SARS-CoV-2 pandemic on the HIV-1 pandemic needs to be evaluated. METHODS: All individuals with newly reported HIV-1 diagnoses from NC State Laboratory of Public Health were enrolled in this prospective observational study, 2018-2021. We used a sequencing-based recency assay to identify recent HIV-1 infections and to determine the days postinfection (DPI) for each person at the time of diagnosis. RESULTS: Sequencing used diagnostic serum samples from 814 individuals with new HIV-1 diagnoses spanning this 4-year period. Characteristics of individuals diagnosed in 2020 differed from those in other years. People of color diagnosed in 2021 were on average 6 months delayed in their diagnosis compared to those diagnosed in 2020. There was a trend that genetic networks were more known for individuals diagnosed in 2021. We observed no major integrase resistance mutations over the course of the study. CONCLUSIONS: SARS-CoV-2 pandemic may contribute to the spread of HIV-1. Public health resources need to focus on restoring HIV-1 testing and interrupting active, ongoing, transmission.

Iterative method for optical modelling of perovskite-based tandem solar cells.

We present an iterative method to model the optical properties of a complete semitransparent perovskite solar cell. It is based on spectroscopic characterizations and accounts for porosity and incoherence effects. We provide the complex refractive indices of each layer, and we identify the main sources of optical losses. The optical model is also coupled to an electrical model of 4T perovskite/silicon tandem solar cells. It allows to evaluate the interplay between the optical and electrical losses, and the balance between the efficiency of the top and bottom cells. These models provide an effective way to design future tandem devices.

Low LAL (Lysosomal Acid Lipase) Expression by Smooth Muscle Cells Relative to Macrophages as a Mechanism for Arterial Foam Cell Formation.

[Figure: see text].

Assessing the added value of group B Streptococcus maternal immunisation in preventing maternal infection and fetal harm: population surveillance study.

OBJECTIVE: To assess the incidence of maternal group B Streptococcus (GBS) infection in England. DESIGN: Population surveillance augmented through data linkage. SETTING: England. POPULATION: All pregnant women accessing the National Health Service (NHS) in England. METHODS: Invasive GBS (iGBS) infections during pregnancy or within 6 weeks of childbirth were identified by linking Public Health England (PHE) national microbiology surveillance data for 2014 to NHS hospital admission records. Capsular serotypes of GBS were determined by reference laboratory typing of clinical isolates from women aged 15-44 years. Post-caesarean section surgical site infection (SSI) caused by GBS was identified in 21 hospitals participating in PHE SSI surveillance (2009-2015). MAIN OUTCOME MEASURES: iGBS rate per 1000 maternities; risk of GBS SSI per 1000 caesarean sections. RESULTS: Of 1601 patients diagnosed with iGBS infections in England in 2014, 185 (12%) were identified as maternal infections, a rate of 0.29 (95% CI 0.25-0.33) per 1000 maternities and representing 83% of all iGBS cases in women aged 18-44 years. Seven (3.8%) were associated with miscarriage. Fetal outcome identified excess rates of stillbirth (3.4 versus 0.5%) and extreme prematurity (<28 weeks of gestation, 3.7 versus 0.5%) compared with national averages (P < 0.001). Caesarean section surveillance in 27 860 women (21 hospitals) identified 47 cases of GBS SSI, with an estimated 4.24 (3.51-5.07) per 1000 caesarean sections, a median time-to-onset of 10 days (IQR 7-13 days) and ten infections that required readmission. Capsular serotype analysis identified a diverse array of strains with serotype III as the most common (43%). CONCLUSIONS: Our assessment of maternal GBS infection in England indicates the potential additional benefit of GBS vaccination in preventing adverse maternal and fetal outcomes.

ß-d-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells.

Mutagenic ribonucleosides can act as broad-based antiviral agents. They are metabolized to the active ribonucleoside triphosphate form and concentrate in genomes of RNA viruses during viral replication. ß-d-N4-hydroxycytidine (NHC, initial metabolite of molnupiravir) is >100-fold more active than ribavirin or favipiravir against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with antiviral activity correlated to the level of mutagenesis in virion RNA. However, NHC also displays host mutational activity in an animal cell culture assay, consistent with RNA and DNA precursors sharing a common intermediate of a ribonucleoside diphosphate. These results indicate highly active mutagenic ribonucleosides may hold risk for the host.

Correlated optical and electrical analyses of inhomogeneous core/shell InGaN/GaN nanowire light emitting diodes.

The performance of core-shell InGaN/GaN nanowire (NW) light emitting diodes (LEDs) can be limited by wire-to-wire electrical inhomogeneities. Here we investigate an array of core-shell InGaN/GaN NWs which are morphologically identical, but present electrical dissimilarities in order to understand how the nanoscale phenomena observed in individual NWs affect the working performance of the whole array. The LED shows a low number of NWs (∼20%) producing electroluminescence under operating conditions. This is related to a presence of a potential barrier at the interface between the NW core and the radially grown n-doped layer, which differently affects the electrical properties of the NWs although they are morphologically identical. The impact of the potential barrier on the performance of the NW array is investigated by correlating multi-scanning techniques, namely electron beam induced current microscopy, electroluminescence mapping and cathodoluminescence analysis. It is found that the main cause of inhomogeneity in the array is related to a non-optimized charge injection into the active region, which can be overcome by changing the contact architecture so that the electrons become injected directly in the n-doped underlayer. The LED with so-called 'front-n-contacting' is developed leading to an increase of the yield of emitting NWs from 20% to 65%.

Pathways of smooth muscle foam cell formation in atherosclerosis.

PURPOSE OF REVIEW: Smooth muscle cells (SMCs) are the major cell type in human atherosclerosis-prone arteries and take up excess lipids, thereby contributing to luminal occlusion. Here we provide a focused review on pathways by which smooth muscle cells (SMCs) can become foam cells in atherosclerosis. RECENT FINDINGS: A synthesis of recent and older investigations provides key mechanistic insights into SMC foam cell formation. LDL and other apoB-containing lipoproteins are modified by a diverse array of oxidative, enzymatic, and nonenzymatic processes present in the arterial intima. These modifications of LDL all promote the aggregation of LDL (agLDL), a key finding from analysis of arterial lesion particles. Scavenger receptor and phagocytic capacity of SMCs can vary greatly, perhaps related to differences in SMC phenotype or in-vitro cell culture environments, and can be increased with exposure to cytokines, growth factors, and cholesterol. Macrophages promote the formation of SMC foam cells in direct or indirect co-culture models. SUMMARY: SMCs contribute significantly to the foam cell population in atherosclerosis. Further investigation and identification of key mechanisms of SMC foam cell formation will help drive new therapeutics to reduce cardiovascular disease.

Correlated optical and structural analyses of individual GaAsP/GaP core-shell nanowires.

We report on the structural and optical properties of GaAs0.7P0.3/GaP core-shell nanowires (NWs) for future photovoltaic applications. The NWs are grown by self-catalyzed molecular beam epitaxy. Scanning transmission electron microscopy (STEM) analyses demonstrate that the GaAsP NW core develops an inverse-tapered shape with a formation of an unintentional GaAsP shell having a lower P content. Without surface passivation, this unintentional shell produces no luminescence because of strong surface recombination. However, passivation of the surface with a GaP shell leads to the appearance of a secondary peak in the luminescence spectrum arising from this unintentional shell. The attribution of the luminescence peaks is confirmed by correlated cathodoluminescence and STEM analyses of the same NW.

Value-Based Care Has Not Resulted in Biased Patient Selection: Analysis of a Single Center's Experience in the Care for Joint Replacement Bundle.

BACKGROUND: Bundled reimbursement models for total knee arthroplasty (TKA) by the Center for Medicare and Medicaid Services have resulted in an effort to decrease the cost of care. However, these models may incentivize bias in patient selection to avoid excess cost of care. We sought to determine the impact of the Comprehensive Care for Joint Replacement (CJR) model at a single center. METHODS: This is a retrospective review of primary TKA patients from July 2015 to December 2017. Patients were stratified by whether or not their surgery was performed before or after implementation of the CJR bundle. Patient demographic data including age, sex, and body mass index were collected in addition to Elixhauser comorbidities and American Society of Anesthesiologists score. In-hospital outcomes were then examined including surgery duration, length of stay, discharge disposition, and direct cost of care. RESULTS: A total of 1248 TKA patients (546 Medicare and 702 commercial insurance) were evaluated, with 27.0% undergoing surgery before the start of the bundle. Compared to patients following implementation of the bundle, there was no significant difference in age, gender, or body mass index. However, pre-CJR Medicare patients were more likely to have fewer Elixhauser comorbidities (P < .001), prolonged length of stay (P < .001), and greater discharges to inpatient facilities (P = .019). There was no significant difference in direct hospital costs or operative service time comparing pre-bundle and post-bundle patients. CONCLUSION: Implementation of the bundled reimbursement model did not result in biased patient selection at our institution; importantly, it also did not result in decreased hospital costs despite apparent improvement in value-based outcome metrics. This should be taken into consideration as future adaptations to reimbursement are made by the Center for Medicare and Medicaid Services.

No Changes in Patient Selection and Value-Based Metrics for Total Hip Arthroplasty After Comprehensive Care for Joint Replacement Bundle Implementation at a Single Center.

BACKGROUND: Alternative payment models for total hip arthroplasty (THA) were initiated by the Center for Medicare and Medicaid Services to decrease overall healthcare cost. The associated shift of financial risk to participating institutions may negatively influence patient selection to avoid high cost of care ("cherry picking," "lemon dropping"). This study evaluated the impact of the Comprehensive Care for Joint Replacement (CJR) model on patient selection, care delivery, and hospital costs at a single care center. METHODS: Patients undergoing a primary THA from 2015-2017 were stratified by insurance type (Medicare and commercial insurance) and whether care was provided before (pre-CJR) or after (post-CJR) CJR bundle implementation. Patient age, gender, and body mass index, Elixhauser comorbidities and American Society of Anesthesiologists scores, were analyzed. Delivery of care variables including surgery duration, discharge disposition, length of stay, and direct hospital costs were compared pre- and post-CJR. RESULTS: A total of 751 THA patients (273 Medicare and 478 commercial Insurance) were evaluated pre-CJR (29%) and post-CJR (71%). Patient demographics were similar (age, gender, BMI); however, commercially insured patients had less comorbidities pre-CJR (P = .033). Medicare patient post-CJR length of stay (P = .010) was reduced with a trend toward discharge to home (P = .019). Surgical time, operating room service time, 90-day readmissions and direct hospital costs were similar pre- and post-CJR. CONCLUSION: There was no differential patient selection after CJR bundle implementation and value-based metrics (surgical time, operating room service time) were not affected. Patients were discharged sooner and more often to home. However, overall direct hospital expenses remained unchanged revealing that any cost savings were for insurance providers, not participating hospitals.

The Role of Malnutrition in Ninety-Day Outcomes After Total Joint Arthroplasty.

BACKGROUND: Research has linked malnutrition to more complications in total joint arthroplasty (TJA) patients. The role of preoperative albumin in predicting length of stay (LOS) and 90-day outcomes remains understudied. Often, an albumin cut-off ≤3.5 g/dL is used as proxy for malnutrition, although this value remains understudied. This preoperative level may be missing some patients at risk for adverse events post TJA. METHODS: TJA patients at a single institution from 2013 to 2018 were reviewed for preoperative albumin level. In total, 4047 cases (total knee arthroplasty: 2058; total hip arthroplasty: 1989) had available data, including 90-day readmissions, 90-day emergency department (ED) visits, and postoperative LOS. RESULTS: About 5.6% experienced a readmission and 9.6% had at least one ED visit within 90 days. Overall prevalence of malnutrition was 3.6%, and this cohort experienced a longer average LOS (3.5 vs 2.2 days, P < .0001) and was more likely to experience a readmission (16% vs 5%, P < .0001) or ED visit (18% vs 9%, P = .0005). Additionally, albumin ≤3.5 g/dL was correlated with more frequent discharge to skilled nursing facility/rehab (30.8% vs 14.7%, P < .0001), increased risk for 90-day readmission with univariable (odds ratio [OR] 1.79, P < .0001) and multivariable logistic regression (OR 1.55, P < .0001), and increased risk for 90-day ED visits with univariable (OR 1.62, P < .0001) and multivariable regression (OR 1.35, P < .0001). The optimal albumin cut-off was 3.94 g/dL in a univariable model for 90-day readmission. CONCLUSION: Screening for malnutrition may serve a role in preoperative evaluation. An albumin cutoff value of 3.5 g/dL may miss some at-risk patients.

An overview of approaches and challenges for retrieving marine inherent optical properties from ocean color remote sensing.

Ocean color measured from satellites provides daily global, synoptic views of spectral waterleaving reflectances that can be used to generate estimates of marine inherent optical properties (IOPs). These reflectances, namely the ratio of spectral upwelled radiances to spectral downwelled irradiances, describe the light exiting a water mass that defines its color. IOPs are the spectral absorption and scattering characteristics of ocean water and its dissolved and particulate constituents. Because of their dependence on the concentration and composition of marine constituents, IOPs can be used to describe the contents of the upper ocean mixed layer. This information is critical to further our scientific understanding of biogeochemical oceanic processes, such as organic carbon production and export, phytoplankton dynamics, and responses to climatic disturbances. Given their importance, the international ocean color community has invested significant effort in improving the quality of satellite-derived IOP products, both regionally and globally. Recognizing the current influx of data products into the community and the need to improve current algorithms in anticipation of new satellite instruments (e.g., the global, hyperspectral spectroradiometer of the NASA Plankton, Aerosol, Cloud, ocean Ecosystem (PACE) mission), we present a synopsis of the current state of the art in the retrieval of these core optical properties. Contemporary approaches for obtaining IOPs from satellite ocean color are reviewed and, for clarity, separated based their inversion methodology or the type of IOPs sought. Summaries of known uncertainties associated with each approach are provided, as well as common performance metrics used to evaluate them. We discuss current knowledge gaps and make recommendations for future investment for upcoming missions whose instrument characteristics diverge sufficiently from heritage and existing sensors to warrant reassessing current approaches.

In situ passivation of GaAsP nanowires.

We report on the structural and optical properties of GaAsP nanowires (NWs) grown by molecular-beam epitaxy. By adjusting the alloy composition in the NWs, the transition energy was tuned to the optimal value required for tandem III-V/silicon solar cells. We discovered that an unintentional shell was also formed during the GaAsP NW growth. The NW surface was passivated by an in situ deposition of a radial Ga(As)P shell. Different shell compositions and thicknesses were investigated. We demonstrate that the optimal passivation conditions for GaAsP NWs (with a gap of 1.78 eV) are obtained with a 5 nm thick GaP shell. This passivation enhances the luminescence intensity of the NWs by 2 orders of magnitude and yields a longer luminescence decay. The luminescence dynamics changes from single exponential decay with a 4 ps characteristic time in non-passivated NWs to a bi-exponential decay with characteristic times of 85 and 540 ps in NWs with GaP shell passivation.

Pet ownership is associated with increased risk of non-atopic asthma and reduced risk of atopy in childhood: findings from a UK birth cohort.

BACKGROUND: Studies have shown an inverse association of pet ownership with allergy but inconclusive findings for asthma. OBJECTIVE: To investigate whether pet ownership during pregnancy and childhood was associated with asthma and atopy at the age of 7 in a UK population-based birth cohort. METHODS: Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) were used to investigate associations of pet ownership at six time points from pregnancy to the age of 7 with asthma, atopy (grass, house dust mite, and cat skin prick test) and atopic vs. non-atopic asthma at the age of 7 using logistic regression models adjusted for child's sex, maternal history of asthma/atopy, maternal smoking during pregnancy, and family adversity. RESULTS: A total of 3768 children had complete data on pet ownership, asthma, and atopy. Compared with non-ownership, continuous ownership of any pet (before and after the age of 3) was associated with 52% lower odds of atopic asthma [odds ratio (OR) 0.48, 95% CI 0.34-0.68]. Pet ownership tended to be associated with increased risk of non-atopic asthma, particularly rabbits (OR 1.61, 1.04-2.51) and rodents (OR 1.86, 1.15-3.01), comparing continuous vs. non-ownership. Pet ownership was consistently associated with lower odds of sensitization to grass, house dust mite, and cat allergens, but rodent ownership was associated with higher odds of sensitization to rodent allergen. Differential effects of pet ownership on atopic vs. non-atopic asthma were evident for all pet types. CONCLUSIONS AND CLINICAL RELEVANCE: Pet ownership during pregnancy and childhood in this birth cohort was consistently associated with a reduced risk of aeroallergen sensitization and atopic asthma at the age of 7, but tended to be associated (particularly for rabbits and rodents) with an increased risk of non-atopic asthma. The opposing effects on atopy vs. non-atopic asthma might be considered by parents when they are deciding whether to acquire a pet.

Tooth counts through growth in diapsid reptiles: implications for interpreting individual and size-related variation in the fossil record.

Tooth counts are commonly recorded in fossil diapsid reptiles and have been used for taxonomic and phylogenetic purposes under the assumption that differences in the number of teeth are largely explained by interspecific variation. Although phylogeny is almost certainly one of the greatest factors influencing tooth count, the relative role of intraspecific variation is difficult, and often impossible, to test in the fossil record given the sample sizes available to palaeontologists and, as such, is best investigated using extant models. Intraspecific variation (largely manifested as size-related or ontogenetic variation) in tooth counts has been examined in extant squamates (lizards and snakes) but is poorly understood in archosaurs (crocodylians and dinosaurs). Here, we document tooth count variation in two species of extant crocodylians (Alligator mississippiensis and Crocodylus porosus) as well as a large varanid lizard (Varanus komodoensis). We test the hypothesis that variation in tooth count is driven primarily by growth and thus predict significant correlations between tooth count and size, as well as differences in the frequency of deviation from the modal tooth count in the premaxilla, maxilla, and dentary. In addition to tooth counts, we also document tooth allometry in each species and compare these results with tooth count change through growth. Results reveal no correlation of tooth count with size in any element of any species examined here, with the exception of the premaxilla of C. porosus, which shows the loss of one tooth position. Based on the taxa examined here, we reject the hypothesis, as it is evident that variation in tooth count is not always significantly correlated with growth. However, growth trajectories of smaller reptilian taxa show increases in tooth counts and, although current samples are small, suggest potential correlates between tooth count trajectories and adult size. Nevertheless, interspecific variation in growth patterns underscores the importance of considering and understanding growth when constructing taxonomic and phylogenetic characters, in particular for fossil taxa where ontogenetic patterns are difficult to reconstruct.