143 research outputs found

    Secular Trends in Nosocomial Bloodstream Infections: Antibiotic-Resistant Bacteria Increase the Total Burden of Infection

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    In this international study, we demonstrate that increasing rates of nosocomial bloodstream infections caused by antibiotic-resistant bacteria do not replace infections caused by antibiotic-susceptible bacteria, but occur in addition to these infections, thereby increasing the total burden of diseas

    An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity

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    Kidney tumours are among the most common solid tumours in children, comprising distinct subtypes differing in many aspects, including cell-of-origin, genetics, and pathology. Pre-clinical cell models capturing the disease heterogeneity are currently lacking. Here, we describe the first paediatric cancer organoid biobank. It contains tumour and matching normal kidney organoids from over 50 children with different subtypes of kidney cancer, including Wilms tumours, malignant rhabdoid tumours, renal cell carcinomas, and congenital mesoblastic nephromas. Paediatric kidney tumour organoids retain key properties of native tumours, useful for revealing patient-specific drug sensitivities. Using single cell RNA-sequencing and high resolution 3D imaging, we further demonstrate that organoid cultures derived from Wilms tumours consist of multiple different cell types, including epithelial, stromal and blastemal-like cells. Our organoid biobank captures the heterogeneity of paediatric kidney tumours, providing a representative collection of well-characterised models for basic cancer research, drug-screening and personalised medicine

    Immunogenicity of an additional mRNA-1273 SARS-CoV-2 vaccination in people with HIV with hyporesponse after primary vaccination

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    Background:The COVIH study is a prospective coronavirus disease 2019 (COVID-19) vaccination study in 1154 people with HIV (PWH), of whom 14% showed reduced antibody levels after primary vaccination. We evaluated whether an additional vaccination boosts immune responses in these hyporesponders. Methods: The primary end point was the increase in antibodies 28 days after additional mRNA-1273 vaccination. Secondary end points included neutralizing antibodies, S-specific T-cell and B-cell responses, and reactogenicity. Results:Of the 66 participants, 40 previously received 2 doses ChAdOx1-S, 22 received 2 doses BNT162b2, and 4 received a single dose Ad26.COV2.S. The median age was 63 years (interquartile range [IQR], 60–66), 86% were male, and median CD4 + T-cell count was 650/μL (IQR, 423–941). The mean S1-specific antibody level increased from 35 binding antibody units (BAU)/ mL (95% confidence interval [CI], 24–46) to 4317 BAU/mL (95% CI, 3275–5360) (P &lt; .0001). Of all participants, 97% showed an adequate response and the 45 antibody-negative participants all seroconverted. A significant increase in the proportion of PWH with ancestral S-specific CD4 + T cells (P = .04) and S-specific B cells (P = .02) was observed. Conclusions:An additional mRNA-1273 vaccination induced a robust serological response in 97% of PWH with a hyporesponse after primary vaccination.</p

    Optically modulated magnetic resonance of erbium implanted silicon

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    Er implanted Si is an important candidate for quantum and photonic applications, but the Er centres involved are poorly understood, which has hindered development of these applications. Here we present the first measurement of the crystal field splitting of the 4I13/2 manifold of Er implanted Si, using a technique we call optically modulated magnetic resonance (OMMR). Crystal field analysis allows us to determine that this splitting originates from a photoluminescence (PL) active O coordinated Er centre with orthorhombic symmetry, which is highly localised with, and magically coupled to, an electron paramagnetic resonance (ERP) active O coordinated Er centre with monoclinic symmetry. The orthorhombic centre has a g-factor in agreement with previous Zeeman measurements, and is associated with a previously unreported acceptor state at ~ Ev+425 cm-1, showing that Er in Si is amphoteric, and not a pure donor, as previously thought. The OMMR mechanism involves transitions from this acceptor state to the 4I13/2 manifold, followed by relaxation to the Zeeman ground state
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