28 research outputs found

    The influence of human genetic variation on early transcriptional responses and protective immunity following immunization with Rotarix vaccine in infants in Ho Chi Minh City in Vietnam : a study protocol for an open single-arm interventional trial [awaiting peer review]

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    Background: Rotavirus (RoV) remains the leading cause of acute gastroenteritis in infants and children aged under five years in both high- and low-middle-income countries (LMICs). In LMICs, RoV infections are associated with substantial mortality. Two RoV vaccines (Rotarix and Rotateq) are widely available for use in infants, both of which have been shown to be highly efficacious in Europe and North America. However, for unknown reasons, these RoV vaccines have markedly lower efficacy in LMICs. We hypothesize that poor RoV vaccine efficacy across in certain regions may be associated with genetic heritability or gene expression in the human host. Methods/design: We designed an open-label single-arm interventional trial with the Rotarix RoV vaccine to identify genetic and transcriptomic markers associated with generating a protective immune response against RoV. Overall, 1,000 infants will be recruited prior to Expanded Program on Immunization (EPI) vaccinations at two months of age and vaccinated with oral Rotarix vaccine at two and three months, after which the infants will be followed-up for diarrheal disease until 18 months of age. Blood sampling for genetics, transcriptomics, and immunological analysis will be conducted before each Rotarix vaccination, 2-3 days post-vaccination, and at each follow-up visit (i.e. 6, 12 and 18 months of age). Stool samples will be collected during each diarrheal episode to identify RoV infection. The primary outcome will be Rotarix vaccine failure events (i.e. symptomatic RoV infection despite vaccination), secondary outcomes will be antibody responses and genotypic characterization of the infection virus in Rotarix failure events. Discussion: This study will be the largest and best powered study of its kind to be conducted to date in infants, and will be critical for our understanding of RoV immunity, human genetics in the Vietnam population, and mechanisms determining RoV vaccine-mediated protection. Registration: ClinicalTrials.gov, ID: NCT03587389. Registered on 16 July 2018

    Minimal residual disease in breast cancer: an overview of circulating and disseminated tumour cells

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    FastHare: Fast Hamiltonian Reduction for Large-scale Quantum Annealing

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    Quantum annealing (QA) that encodes optimization problems into Hamiltonians remains the only near-term quantum computing paradigm that provides sufficient many qubits for real-world applications. To fit larger optimization instances on existing quantum annealers, reducing Hamiltonians into smaller equivalent Hamiltonians provides a promising approach. Unfortunately, existing reduction techniques are either computationally expensive or ineffective in practice. To this end, we introduce a novel notion of non-separable~group, defined as a subset of qubits in a Hamiltonian that obtains the same value in optimal solutions. We develop a theoretical framework on non-separability accordingly and propose FastHare, a highly efficient reduction method. FastHare, iteratively, detects and merges non-separable groups into single qubits. It does so within a provable worst-case time complexity of only O(αn2)O(\alpha n^2), for some user-defined parameter α\alpha. Our extensive benchmarks for the feasibility of the reduction are done on both synthetic Hamiltonians and 3000+ instances from the MQLIB library. The results show FastHare outperforms the roof duality, the implemented reduction method in D-Wave's SDK library, with 3.6x higher average reduction ratio. It demonstrates a high level of effectiveness with an average of 62% qubits saving and 0.3s processing time, advocating for Hamiltonian reduction as an inexpensive necessity for QA

    Blockchain-based Secure Client Selection in Federated Learning

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    Despite the great potential of Federated Learning (FL) in large-scale distributed learning, the current system is still subject to several privacy issues due to the fact that local models trained by clients are exposed to the central server. Consequently, secure aggregation protocols for FL have been developed to conceal the local models from the server. However, we show that, by manipulating the client selection process, the server can circumvent the secure aggregation to learn the local models of a victim client, indicating that secure aggregation alone is inadequate for privacy protection. To tackle this issue, we leverage blockchain technology to propose a verifiable client selection protocol. Owing to the immutability and transparency of blockchain, our proposed protocol enforces a random selection of clients, making the server unable to control the selection process at its discretion. We present security proofs showing that our protocol is secure against this attack. Additionally, we conduct several experiments on an Ethereum-like blockchain to demonstrate the feasibility and practicality of our solution.Comment: IEEE ICBC 202

    Trypanosoma evansi and Trypanosomosis in Vietnam

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    Epidemiological Survey on Trypanosoma evansi Infection in Vietnam

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    The validation and utility of a quantitative one-step multiplex RT real-time PCR targeting Rotavirus A and Norovirus

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    Rotavirus (RoV) and Norovirus (NoV) are the main causes of viral gastroenteritis. Currently, there is no validated multiplex real-time PCR that can detect and quantify RoV and NoV simultaneously. The aim of the study was to develop, validate, and internally control a multiplex one-step RT real-time PCR to detect and quantify RoV and NoV in stool samples. PCR sensitivity was assessed by comparing amplification against the current gold standard, enzyme immunoassay (EIA), on stool samples from 94 individuals with diarrhea and 94 individuals without diarrhea. PCR detected 10% more RoV positive samples than EIA in stools samples from patients with diarrhea. PCR detected 23% more NoV genogroup II positive samples from individuals with diarrhea and 9% more from individuals without diarrhea than EIA, respectively. Genotyping of the PCR positive/EIA negative samples suggested the higher rate of PCR positivity, in comparison to EIA, was due to increased sensitivity, rather than nonspecific hybridization. Quantitation demonstrated that the viral loads of RoV and NoV in the stools of diarrheal patients were an order of magnitude greater than in individuals without diarrhea. This internally controlled real-time PCR method is robust, exhibits a high degree of reproducibility, and may have a greater utility and sensitivity than commercial EIA kits. </p

    Evaluation of the Luminex xTAG Respiratory Viral Panel FAST v2 assay for detection of multiple respiratory viral pathogens in nasal and throat swabs in Vietnam

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    Background Acute respiratory infections (ARI) are among the leading causes of hospitalization in children ≤5 years old. Rapid diagnostics of viral pathogens is essential to avoid unnecessary antibiotic treatment, thereby slowing down antibiotic-resistance. We evaluated the diagnostic performance of the Luminex xTAG Respiratory Viral Panel FAST v2 against viral specific PCR as reference assays for ARI in Vietnam. Methods Four hundred and forty two nose and throat swabs were collected in viral transport medium, and were tested with Luminex xTAG Respiratory Viral Panel FAST v2. Multiplex RT-PCR and single RT-PCR were used as references. Results Overall, sensitivity of the Luminex against reference assays was 91.8%, 95% CI 88.1-94.7 (270/294), whilst 112/6336 (1.8%, 95% CI, 1.4-2.1) of pathogens were detected by the Luminex, but not by reference assays. Frequency of pathogens detected by Luminex and reference assays was 379 and 292, respectively. The diagnostic yield was 66.7% (295/442, 95%CI 62.1-71.1%) for the Luminex assay and 54.1% (239/442, 95% CI, 49.3-58.8%) for reference assays. The Luminex kit had higher yields for all viruses except influenza B virus, respiratory syncytial virus, and human bocavirus. High agreements between both methods [mean (range): 0.91 (0.83-1.00)] were found for 10/15 viral agents. Conclusions The Luminex assay is a high throughput multiplex platform for rapid detection of common viral pathogens causing ARI. Although the current high cost may prevent Luminex assays from being widely used, especially in limited resource settings where ARI are felt most, its introduction in clinical diagnostics may help reduce unnecessary use of antibiotic prescription.</p
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