We report a superspreading event of severe acute respiratory syndrome coronavirus 2 infection initiated at a bar in Vietnam with evidence of symptomatic and asymptomatic transmission, based on ...ministry of health reports, patient interviews, and whole-genome sequence analysis. Crowds in enclosed indoor settings with poor ventilation may be considered at high risk for transmission.
Abstract
Background
Little is known about the natural history of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Methods
We conducted a prospective study at a ...quarantine center for coronavirus disease 2019 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with reverse-transcription polymerase chain reaction (RT-PCR)–confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrollment and daily nasopharyngeal/throat swabs (NTSs) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals.
Results
Between 10 March and 4 April 2020, 14 000 quarantined people were tested for SARS-CoV-2; 49 were positive. Of these, 30 participated in the study: 13 (43%) never had symptoms and 17 (57%) were symptomatic. Seventeen (57%) participants imported cases. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS collected at enrollment (8/13 62% vs 17/17 100%; P = .02). SARS-CoV-2 RNA was detected in 20 of 27 (74%) available saliva samples (7 of 11 64% in the asymptomatic group and 13 of 16 81% in the symptomatic group; P = .56). Analysis of RT-PCR positivity probability showed that asymptomatic participants had faster viral clearance than symptomatic participants (P < .001 for difference over the first 19 days). This difference was most pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared to transmit SARS-CoV-2 to 4 contacts.
Conclusions
Asymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTSs. The NTS viral loads fall faster in asymptomatic individuals, but these individuals appear able to transmit the virus to others.
Forty-three percent (13/30) of confirmed SARS-CoV-2–infected individuals were asymptomatic, with the virus detected in both saliva and nasopharyngeal/throat swabs. Viral clearance was faster in asymptomatic individuals, but they still appeared able to pass the infection to others.
Abstract
Most of the existing chest X-ray datasets include labels from a list of findings without specifying their locations on the radiographs. This limits the development of machine learning ...algorithms for the detection and localization of chest abnormalities. In this work, we describe a dataset of more than 100,000 chest X-ray scans that were retrospectively collected from two major hospitals in Vietnam. Out of this raw data, we release 18,000 images that were manually annotated by a total of 17 experienced radiologists with 22 local labels of rectangles surrounding abnormalities and 6 global labels of suspected diseases. The released dataset is divided into a training set of 15,000 and a test set of 3,000. Each scan in the training set was independently labeled by 3 radiologists, while each scan in the test set was labeled by the consensus of 5 radiologists. We designed and built a labeling platform for DICOM images to facilitate these annotation procedures. All images are made publicly available in DICOM format along with the labels of both the training set and the test set.
Background. The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)—associated tuberculous meningitis is unknown. Methods. We conducted a randomized, ...double-blind, placebo-controlled trial of immediate versus deferred ART in patients with HIV-associated tuberculous meningitis to determine whether immediate ART reduced the risk of death. Antiretroviral drugs (zidovudine, lamivudine, and efavirenz) were started either at study entry or 2 months after randomization. All patients were treated with standard antituberculosis treatment, adjunctive dexamethasone, and prophylactic co-trimoxazole and were followed up for 12 months. We conducted intention-to-treat, perprotocol, and prespecified subgroup analyses. Results. A total of 253 patients were randomized, 127 in the immediate ART group and 126 in the deferred ART group; 76 and 70 patients died within 9 months in the immediate and deferred ART groups, respectively. Immediate ART was not significantly associated with 9-month mortality (hazard ratio HR, 1.12; 95% confidence interval CI,.81-1.55; P = .50) or the time to new AIDS events or death (HR, 1.16; 95% CI,.87-1.55; P = .31). The percentage of patients with severe (grade 3 or 4) adverse events was high in both arms (90% in the immediate ART group and 89% in the deferred ART group; P = .84), but there were significantly more grade 4 adverse events in the immediate ART arm (102 in the immediate ART group vs 87 in the deferred ART group; P = .04). Conclusions. Immediate ART initiation does not improve outcome in patients presenting with HIV-associated tuberculous meningitis. There were significantly more grade 4 adverse events in the immediate ART arm, supporting delayed initiation of ART in HIV-associated tuberculous meningitis.
•A micromechanics-based numerical model of ductile materials failure is developed.•The void growth, necking coalescence and shearing coalescence phases are competing.•This combination accounts for ...the triaxiality, Lode variable and shear effects.•A multiple-variable nonlocal implicit formulation regularizes the problem.•Cup-cone and slant fractures are captured for round and plane strain specimens.
An advanced modeling framework is developed for predicting the failure of ductile materials relying on micromechanics, physical ingredients, and robust numerical methods. The approach is based on a hyperelastic finite strain multi-surface constitutive model with multiple nonlocal variables. The three distinct nonlocal solutions for the expansion of voids embedded in an elastoplastic matrix are considered: a void growth phase governed by the Gurson–Tvergaard–Needleman yield surface, a void necking coalescence phase governed by a heuristic extension of the Thomason yield surface based on the maximum principal stress, and a competing void shearing coalescence phase triggered by the maximum shear stress. The first solution considers the diffused plastic deformation around the voids while the last two solutions correspond to a state of plastic localization between neighboring voids. This combination captures the Lode variable and shear effects, which play important roles in dictating the damage evolution rates. The implicit nonlocal formulation with multiple nonlocal variables, including the volumetric and deviatoric parts of the plastic strain, and the mean equivalent plastic strain of the matrix, regularizes the problem of the loss of solution uniqueness when material softening occurs whatever the localization mechanism. The predictive capability of the proposed model is demonstrated through different numerical simulations in which complex failure patterns such as slant and cup-cone of respectively plane strain and axisymmetric samples under tensile loading conditions develop.
Drug delivery to central nervous system (CNS) diseases is very challenging since the presence of the innate blood–brain barrier (BBB) and the blood-cerebrospinal fluid barrier that impede drug ...delivery. Among new strategies to overcome these limitations and successfully deliver drugs to the CNS, nanotechnology-based drug delivery platform, offers potential therapeutic approach for the treatment of some common neurological disorders like Alzheimer’s disease, frontotemporal dementia, amyotrophic lateral sclerosis, Parkinson’s disease, Huntington’s disease. This review aimed to highlight advances in research on the development of nano-based therapeutics for their implications in therapy of CNS disorders. The challenges during clinical translation of nanomedicine from bench to bed side is also discussed.
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•Summarize current strategies and new trends of CNS drug.•Emphasis on nanotechnology-based drug delivery systems for CNS management.•Advantages of the nanomedicine therapeutics.•Current trends and challenges in the clinical translation of nanomedicine for CNS disorders.
The failure process of ductile porous materials is simulated by representing the damage nucleation, growth and coalescence stages up to crack initiation and propagation using a physically-based ...constitutive model. In particular, a non-local damage to crack transition framework is developed to predict the fracture under various loading conditions while minimising case-dependent calibration process. The formulation is based on a discontinuous Galerkin method, making it computationally efficient and scalable. The initial stable damage process is simulated using an implicit non-local Gurson-Tvergaard-Needleman (GTN) model ensuring solution uniqueness beyond the onset of softening. Once the coalescence criterion is satisfied, which can physically arise before or during the softening stage, a cohesive band is introduced. Within the cohesive band, a void coalescence-based governing law is solved, accounting for the stress triaxiality state and material history, in order to capture the near crack tip failure process in a micromechanically sound way. Two coalescence models are then successively considered and compared. First, with a view to model verification towards literature results, a numerical coalescence model detects crack initiation at loss of ellipticity of a local model, and the crack opening is governed by ad-hoc parameters of the GTN model. Alternatively, the Thomason criterion is used to detect crack nucleation during the softening stage while the Thomason coalescence model governs the crack opening process. This latter model is able to reproduce slant and cup-cone failure modes in plane-strain and axisymmetric specimens, respectively.
•A damage to crack transition framework is developed for ductile failure.•A non-local porous plastic model combines the Gurson and Thomason models.•A cohesive band model captures triaxiality effects during crack propa-gation.•Slant fracture is captured for plane strain specimen in agreement with experiments.•Cup-cone fracture is predicted for round bars in agreement with exper-iments.
Tumor necrosis factor alpha (TNF‐α) is an inflammatory cytokine produced during acute inflammation. Few studies have evaluated the association between serum TNF‐α and its receptors and their clinical ...outcomes in hemodialysis patients. However, a study assessing patients using a low‐flux dialyzer reuse has not been conducted yet. The serum TNF‐α concentrations of 319 prevalent hemodialysis patients (mean age, 45 ± 15 years; median duration of hemodialysis, 48 interquartile range, 26‐79 months; 185 males and 134 females) was examined to predict their 3‐year mortality. The patients were divided into tertiles according to their serum TNF‐α concentrations: T1 (n = 106; serum TNF‐α concentration, <41.22 pg/mL), T2 (n = 106; serum TNF‐α level, from 41.22 to 67.28 pg/mL), and T3 (n = 107; serum TNF‐α concentration, ≥ 67.29 pg/mL). During the 36‐month follow‐up period, a total of 50 (15.7%) patients died from all causes. The Kaplan‐Meier analysis revealed that the all‐cause mortality in T3 was significantly higher compared to that in T1 and T2 (log‐rank test, P < .001). The serum TNF‐α level was a significant predictor for all‐cause mortality (area under the curve = 0.887, P < .001, cutoff value, 89.812 pg/mL, sensitivity = 76%, specificity = 96.3%). The serum TNF‐α level was a better predictor of mortality than the duration of hemodialysis and serum albumin, serum high‐sensitivity C‐reactive protein, and serum beta‐2 microglobulin concentrations. The serum TNF‐α concentration was a good predictor of the 3‐year mortality in low‐flux hemodialysis patients.
In this paper, we prove that such a Meir-Keeler contraction on a complete b-metric space with a continuous b-metric is fixed point free. The counterexample answers an early stated question in ...b-metric fixed point theory 4. Next, by adding the increasing property of δ(ε), we prove such Meir-Keeler contraction on a complete b-metric space has a unique fixed point.
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