Low temperature thermal oxidation of epitaxial 3C-SiC

Silicon Carbide (SiC) is a wide-bandgap semiconductor which has promising potential as a future material for power electronics devices such as metal-oxide-semiconductor field effect transistors (MOSFETs). The aim of this project was to take cubic SiC (3C-SiC) grown on silicon (Si) substrates by reduced-pressure chemical vapour deposition (RPCVD) and investigate whether low-temperature (< 1000 ⁰C) dry oxidation is a suitable method for growing the dielectric oxide layers vital for device fabrication. To this end, heteroepitaxially grown 3C-SiC was oxidised at 985 ⁰C and a range of physical and electrical characterisation techniques were employed to assess the grown oxide. X-ray reflectance (XRR) and cross-sectional transmission electron microscopy (X-TEM) analysis suggested a growth rate of around 4.08 × 10-2 nm/min, comparable to that achieved on 4H-SiC. Qualitative analysis showed that this oxide closely followed the surface morphology of the 3C-SiC, and atomic force microscopy (AFM) proved that the oxide did not significantly alter the surface roughness of the as-grown 3C-SiC epilayers. X-ray photoelectron spectroscopy (XPS) and secondary ion mass spectroscopy (SIMS) showed that the oxide had carbon (C) distributed inhomogeneously throughout the oxide, which may have served as charge traps at the oxide/3C-SiC interface and contributed to leakage through the oxide by trap-assisted tunnelling (TAT). The highest concentration of C was at the interface, totalling 25% of the material present. Capacitance-voltage (CV), conductance-voltage (GV), and current-voltage (IV) analysis provided information about the electrical properties of the grown oxide. While a small inversion population was observed in the CV data, this quickly collapsed under negative bias. Relatively high leakage current through the oxide is the suspected cause of this. While leakage was high, the oxide/3C-SiC interface showed a relatively small interface state density (Dit) of 1 × 1010 cm-2eV-1, which is comparable to that seen on similar material after post-oxidation annealing (POA), despite the fact that none was performed on this material. POA may further improve this Ditfigure by up to an order of magnitude. In summary, this work provides some evidence that heteroepitaxially grown 3C-SiC is a viable material for power device applications, but optimisation of the oxidation method and post-oxidation treatment is required to make this material realise its full potential

Wastewater Analysis of Mpox Virus in a City With Low Prevalence of Mpox Disease: an Environmental Surveillance Study

BACKGROUND: Tracking infectious diseases at the community level is challenging due to asymptomatic infections and the logistical complexities of mass surveillance. Wastewater surveillance has emerged as a valuable tool for monitoring infectious disease agents including SARS-CoV-2 and Mpox virus. However, detecting the Mpox virus in wastewater is particularly challenging due to its relatively low prevalence in the community. In this study, we aim to characterize three molecular assays for detecting and tracking the Mpox virus in wastewater from El Paso, Texas, during February and March 2023. METHODS: In this study, a combined approach utilizing three real-time PCR assays targeting the C22L, F3L, and F8L genes and sequencing was employed to detect and track the Mpox virus in wastewater samples. The samples were collected from four sewersheds in the City of El Paso, Texas, during February and March 2023. Wastewater data was compared with reported clinical case data in the city. FINDINGS: Mpox virus DNA was detected in wastewater from all the four sewersheds, whereas only one Mpox case was reported during the sampling period. Positive signals were still observed in multiple sewersheds after the Mpox case was identified. Higher viral concentrations were found in the pellet than in the supernatant of wastewater. Notably, an increasing trend in viral concentration was observed approximately 1-2 weeks before the reporting of the Mpox case. Further sequencing and epidemiological analysis provided supporting evidence for unreported Mpox infections in the city. INTERPRETATION: Our analysis suggests that the Mpox cases in the community is underestimated. The findings emphasize the value of wastewater surveillance as a public health tool for monitoring infectious diseases even in low-prevalence areas, and the need for heightened vigilance to mitigate the spread of Mpox disease for safeguarding global health. FUNDING: Center of Infectious Diseases at UTHealth, the University of Texas System, and the Texas Epidemic Public Health Institute. The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of these funding organizations

Multiple RSV strains infecting HEp-2 and A549 cells reveal cell line-dependent differences in resistance to RSV infection

Background: Respiratory syncytial virus (RSV) is the major viral driver of a global pediatric respiratory disease burden disproportionately borne by the poor1. Thus, RSV, like SARS-CoV-2, combines with congenital and environmental and host-history-dependent factors to create a spectrum of disease with greatest severity most frequently occurring in those least able to procure treatment. Methods: Here we apply whole genome sequencing and a suite of other molecular biological techniques to survey host-virus dynamics in infections of two distinct cell lines (HEp2 and A549) with four strains representative of known RSV genetic diversity. Results: We observed non-gradient patterns of RSV gene expression and a single major difference in transcriptional readthrough correlating with a deep split in the RSV phylogenetic tree. We also observed increased viral replication in HEp2 cells along with a pro-inflammatory host-response; and decreased viral replication in A549 cells with a more potent antiviral response in host gene expression and levels of secreted cytokines. Conclusions: Our findings suggest HEp2 and A549 cell lines can be used as complementary models of host response leading to more or less severe RSV disease. In vitro perturbations inspired by actual environmental and host-history-dependent factors associated with greater disease can be tested for their ability to shift the antiviral response of A549 cells to the more pro-inflammatory response of HEp2 cells. Such studies would help illuminate the tragic costs of poverty and suggest public health-level interventions to reduce the global disease burden from RSV and other respiratory viruses

Fully Resolved assembly of Cryptosporidium Parvum

BACKGROUND: Cryptosporidium parvum is an apicomplexan parasite commonly found across many host species with a global infection prevalence in human populations of 7.6%. Understanding its diversity and genomic makeup can help in fighting established infections and prohibiting further transmission. The basis of every genomic study is a high-quality reference genome that has continuity and completeness, thus enabling comprehensive comparative studies. FINDINGS: Here, we provide a highly accurate and complete reference genome of Cryptosporidium parvum. The assembly is based on Oxford Nanopore reads and was improved using Illumina reads for error correction. We also outline how to evaluate and choose from different assembly methods based on 2 main approaches that can be applied to other Cryptosporidium species. The assembly encompasses 8 chromosomes and includes 13 telomeres that were resolved. Overall, the assembly shows a high completion rate with 98.4% single-copy BUSCO genes. CONCLUSIONS: This high-quality reference genome of a zoonotic IIaA17G2R1 C. parvum subtype isolate provides the basis for subsequent comparative genomic studies across the Cryptosporidium clade. This will enable improved understanding of diversity, functional, and association studies

'I Just Stopped Going': A Mixed Methods Investigation Into Types of Therapy Dropout in Adolescents With Depression

What does it mean to ‘drop out’ of therapy? Many definitions of ‘dropout’ have been proposed, but the most widely accepted is the client ending treatment without agreement of their therapist. However, this is in some ways an external criterion that does not take into account the client’s experience of therapy, or reasons for ending it prematurely. This study aimed to identify whether there were more meaningful categories of dropout than the existing dropout definition, and to test whether this refined categorization of dropout was associated with clinical outcomes. This mixed-methods study used a subset of data from the IMPACT trial, which investigated psychological therapies for adolescent depression. Adolescents were randomly allocated to a treatment arm (Brief Psychosocial Intervention; Cognitive-Behavioral Therapy; Short-Term Psychoanalytic Psychotherapy). The sample for this study comprised 99 adolescents, aged 11–17 years. Thirty-two were classified as having dropped out of treatment and participated in post-therapy qualitative interviews about their experiences of therapy. For 26 dropout cases, the therapist was also interviewed. Sixty-seven cases classified as having completed treatment were included to compare their outcomes to dropout cases. Interview data for dropout cases were analyzed using ideal type analysis. Three types of dropout were constructed: ‘dissatisfied’ dropout, ‘got-what-they-needed’ dropout, and ‘troubled’ dropout. ‘Dissatisfied’ dropouts reported stopping therapy because they did not find it helpful. ‘Got-what-they-needed’ dropouts reported stopping therapy because they felt they had benefitted from therapy. ‘Troubled’ dropouts reported stopping therapy because of a lack of stability in their lives. The findings indicate the importance of including the perspective of clients in definitions of drop out, as otherwise there is a risk that the heterogeneity of ‘dropout’ cases may mask more meaningful distinctions. Clinicians should be aware of the range of issues experienced by adolescents in treatment that lead to disengagement. Our typology of dropout may provide a framework for clinical decision-making in managing different types of disengagement from treatment

Wastewater Sequencing Reveals Community and Variant Dynamics of the Collective Human Virome

Wastewater is a discarded human by-product, but its analysis may help us understand the health of populations. Epidemiologists first analyzed wastewater to track outbreaks of poliovirus decades ago, but so-called wastewater-based epidemiology was reinvigorated to monitor SARS-CoV-2 levels while bypassing the difficulties and pit falls of individual testing. Current approaches overlook the activity of most human viruses and preclude a deeper understanding of human virome community dynamics. Here, we conduct a comprehensive sequencing-based analysis of 363 longitudinal wastewater samples from ten distinct sites in two major cities. Critical to detection is the use of a viral probe capture set targeting thousands of viral species or variants. Over 450 distinct pathogenic viruses from 28 viral families are observed, most of which have never been detected in such samples. Sequencing reads of established pathogens and emerging viruses correlate to clinical data sets of SARS-CoV-2, influenza virus, and monkeypox viruses, outlining the public health utility of this approach. Viral communities are tightly organized by space and time. Finally, the most abundant human viruses yield sequence variant information consistent with regional spread and evolution. We reveal the viral landscape of human wastewater and its potential to improve our understanding of outbreaks, transmission, and its effects on overall population health

Performance evaluation of Sanger sequencing for the diagnosis of primary hyperoxaluria and comparison with targeted next generation sequencing

Definitive diagnosis of primary hyperoxaluria (PH) currently utilizes sequential Sanger sequencing of the AGXT, GRPHR, and HOGA1 genes but efficacy is unproven. This analysis is time-consuming, relatively expensive, and delays in diagnosis and inappropriate treatment can occur if not pursued early in the diagnostic work-up. We reviewed testing outcomes of Sanger sequencing in 200 consecutive patient samples referred for analysis. In addition, the Illumina Truseq custom amplicon system was evaluated for paralleled next-generation sequencing (NGS) of AGXT,GRHPR, and HOGA1 in 90 known PH patients. AGXT sequencing was requested in all patients, permitting a diagnosis of PH1 in 50%. All remaining patients underwent targeted exon sequencing of GRHPR and HOGA1 with 8% diagnosed with PH2 and 8% with PH3. Complete sequencing of both GRHPR and HOGA1 was not requested in 25% of patients referred leaving their diagnosis in doubt. NGS analysis showed 98% agreement with Sanger sequencing and both approaches had 100% diagnostic specificity. Diagnostic sensitivity of Sanger sequencing was 98% and for NGS it was 97%. NGS has comparable diagnostic performance to Sanger sequencing for the diagnosis of PH and, if implemented, would screen for all forms of PH simultaneously ensuring prompt diagnosis at decreased cost

Wastewater pandemic preparedness: Toward an end-to-end pathogen monitoring program

Molecular analysis of public wastewater has great potential as a harbinger for community health and health threats. Long-used to monitor the presence of enteric viruses, in particular polio, recent successes of wastewater as a reliable lead indicator for trends in SARS-CoV-2 levels and hospital admissions has generated optimism and emerging evidence that similar science can be applied to other pathogens of pandemic potential (PPPs), especially respiratory viruses and their variants of concern (VOC). However, there are substantial challenges associated with implementation of this ideal, namely that multiple and distinct fields of inquiry must be bridged and coordinated. These include engineering, molecular sciences, temporal-geospatial analytics, epidemiology and medical, and governmental and public health messaging, all of which present their own caveats. Here, we outline a framework for an integrated, state-wide, end-to-end human pathogen monitoring program using wastewater to track viral PPPs