Natural human exhalation flows such as coughing, sneezing and breathing can be considered as 'jet-like' airflows in the sense that they are produced from a single source in a single exhalation ...effort, with a relatively symmetrical, conical geometry. Although coughing and sneezing have garnered much attention as potential, explosive sources of infectious aerosols, these are relatively rare events during daily life, whereas breathing is necessary for life and is performed continuously. Real-time shadowgraph imaging was used to visualise and capture high-speed images of healthy volunteers sneezing and breathing (through the nose - nasally, and through the mouth - orally). Six volunteers, who were able to respond to the pepper sneeze stimulus, were recruited for the sneezing experiments (2 women: 27.5±6.36 years; 4 men: 29.25±10.53 years). The maximum visible distance over which the sneeze plumes (or puffs) travelled was 0.6 m, the maximum sneeze velocity derived from these measured distances was 4.5 m/s. The maximum 2-dimensional (2-D) area of dissemination of these sneezes was 0.2 m(2). The corresponding derived parameter, the maximum 2-D area expansion rate of these sneezes was 2 m(2)/s. For nasal breathing, the maximum propagation distance and derived velocity were 0.6 m and 1.4 m/s, respectively. The maximum 2-D area of dissemination and derived expansion rate were 0.11 m(2) and 0.16 m(2)/s, respectively. Similarly, for mouth breathing, the maximum propagation distance and derived velocity were 0.8 m and 1.3 m/s, respectively. The maximum 2-D area of dissemination and derived expansion rate were 0.18 m(2) and 0.17 m(2)/s, respectively. Surprisingly, a comparison of the maximum exit velocities of sneezing reported here with those obtained from coughing (published previously) demonstrated that they are relatively similar, and not extremely high. This is in contrast with some earlier estimates of sneeze velocities, and some reasons for this difference are discussed.
Coronavirus disease 2019 (COVID-19) is an emerging infectious disease of pandemic proportions. Healthcare workers in Singapore working in high-risk areas were mandated to wear personal protective ...equipment (PPE) such as N95 face mask and protective eyewear while attending to patients.
We sought to determine the risk factors associated with the development of de novo PPE-associated headaches as well as the perceived impact of these headaches on their personal health and work performance. The impact of COVID-19 on pre-existing headache disorders was also investigated.
This is a cross-sectional study among healthcare workers at our tertiary institution who were working in high-risk hospital areas during COVID-19. All respondents completed a self-administered questionnaire.
A total of 158 healthcare workers participated in the study. Majority 126/158 (77.8%) were aged 21-35 years. Participants included nurses 102/158 (64.6%), doctors 51/158 (32.3%), and paramedical staff 5/158 (3.2%). Pre-existing primary headache diagnosis was present in about a third 46/158 (29.1%) of respondents. Those based at the emergency department had higher average daily duration of combined PPE exposure compared to those working in isolation wards 7.0 (SD 2.2) vs 5.2 (SD 2.4) hours, P < .0001 or medical ICU 7.0 (SD 2.2) vs 2.2 (SD 0.41) hours, P < .0001. Out of 158 respondents, 128 (81.0%) respondents developed de novo PPE-associated headaches. A pre-existing primary headache diagnosis (OR = 4.20, 95% CI 1.48-15.40; P = .030) and combined PPE usage for >4 hours per day (OR 3.91, 95% CI 1.35-11.31; P = .012) were independently associated with de novo PPE-associated headaches. Since COVID-19 outbreak, 42/46 (91.3%) of respondents with pre-existing headache diagnosis either "agreed" or "strongly agreed" that the increased PPE usage had affected the control of their background headaches, which affected their level of work performance.
Most healthcare workers develop de novo PPE-associated headaches or exacerbation of their pre-existing headache disorders.
No standard of care for mucosal melanoma (MM) in the adjuvant setting has been established. Meanwhile, relapse-free survival (RFS) is only ∼5 months after surgery alone. This phase II trial aimed to ...compare toripalimab versus high-dose interferon-α2b (HDI) as an adjuvant therapy for resected MM.
From July 2017 to May 2019, 145 patients with resected MM were randomized (1 : 1) to receive HDI (n = 72) or toripalimab (n = 73) for 1 year until disease relapse/distant metastasis, unacceptable toxicity, or withdrawal of consent. The primary endpoint was RFS. The secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS), and safety.
After a median follow-up of 26.3 months, the number of RFS, OS, and DMFS events was 51 versus 46, 33 versus 29, and 49 versus 44 in the toripalimab arm and the HDI arm, respectively. The median RFS was 13.6 95% confidence interval (CI) 8.31-19.02 months and 13.9 (95% CI 8.28-19.61) months in the toripalimab arm and the HDI arm, respectively. The DMFS was not significantly different between the two arms hazard ratio (HR) 1.00; 95% CI 0.65-1.54. The median OS was 35.1 months (95% CI 27.93 months-not reached) in the toripalimab arm, with no significant difference in all-cause death (HR 1.11, 95% CI 0.66-1.84) for the two arms. The median sums of the patients’ actual infusion doses were 3672 mg and 1054.5 MIU in the toripalimab arm and the HDI arm, respectively. The incidence of treatment-emergent adverse events with a grade ≥3 was much higher in the HDI arm than in the toripalimab arm (87.5% versus 27.4%).
Toripalimab showed a similar RFS and a more favorable safety profile than HDI, both better than historical data, suggesting that toripalimab might be the better treatment option. However, additional translational studies and better treatment regimens are still warranted to improve the clinical outcome of MM.
•This is the first study to compare toripalimab versus HDI as adjuvant therapy for resected MM.•In PD-L1-positive patients, the median RFS was ∼6 months longer in the toripalimab arm than in the HDI arm.•The incidence of TEAEs with a grade ≥3 was much higher in the HDI arm than in the toripalimab arm.•Both interventions have potential for MM; toripalimab might be the better treatment option.
A topological meron features a non-coplanar structure, whose order parameters in the core region are perpendicular to those near the perimeter. A meron is half of a skyrmion, and both have potential ...applications for information carrying and storage. Although merons and skyrmions in ferromagnetic materials can be readily obtained via inter-spin interactions, their behaviour and even existence in ferroelectric materials are still elusive. Here we observe using electron microscopy not only the atomic morphology of merons with a topological charge of 1/2, but also a periodic meron lattice in ultrathin PbTiO
films under tensile epitaxial strain on a SmScO
substrate. Phase-field simulations rationalize the formation of merons for which an epitaxial strain, as a single alterable parameter, plays a critical role in the coupling of lattice and charge. This study suggests that by engineering strain at the nanoscale it should be possible to fabricate topological polar textures, which in turn could facilitate the development of nanoscale ferroelectric devices.
Blood-circulating microRNAs (miRNAs) have been reported to be used as potential biomarkers in various cancers. MiR-101 has been found to act as a tumor suppressor in many tumor types, but little is ...known for osteosarcoma. The purpose of this study was to investigate miR-101 expression in osteosarcoma patients and assess its correlation with clinical features and prognosis. Serum samples from 152 osteosarcoma patients and 70 healthy controls were detected using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The data showed that miR-101 expression levels were remarkably underexpressed in serum samples from osteosarcoma patients compared to controls, and the post-treatment serum miR-101 expression was significantly higher than that in the pre-treatment expression. Low serum miR-101 expression was positively associated with advanced clinical stage and distant metastasis. Receiver operating characteristic (ROC) curve analysis showed that serum miR-101 could serve as a useful marker for osteosarcoma diagnosis, with a high sensitivity and specificity. Moreover, patients with high miR-101 expression had longer overall survival and recurrence free survival than those with low miR-101 expression. In addition, both univariate and multivariate analyses showed that serum miR-101 downregulation was associated with shorter overall survival and recurrence free survival. Our present results implicated serum miR-101 might be a useful biomarker for the clinical diagnosis and prognosis of osteosarcoma.
Tumor-associated macrophages (TAMs) play an essential role in metastasis. However, what enables TAMs to have a superior capacity to establish pre-metastatic microenvironment in distant organs is ...unclear. Here we have begun to uncover the effects of cytochrome P450 (CYP) 4A in TAMs on lung pre-metastatic niche formation and metastasis. CYP4A
TAM infiltration was positively associated with metastasis, pre-metastatic niche formation and poor prognosis in breast cancer patients. The pharmacological inhibition of CYP4A reduced lung pre-metastatic niche formation (evidenced by a decrease in vascular endothelial growth factor receptor 1 positive (VEGFR1
) myeloid cell recruitment and pro-metastatic protein expression) and metastatic burden, accompanied with TAM polarization away from the M2 phenotype in spontaneous metastasis models of 4T1 breast cancer and B16F10 melanoma. Co-implantation of 4T1 cells with CYP4A10
macrophages promoted lung pre-metastatic niche formation and metastasis. Depletion of TAMs disrupted lung pre-metastatic niches and thereby prevented metastasis. Treatment with the CM from CYP4A10
M2 macrophages (M2) increased pre-metastatic niche formation and metastatic burden in the lungs, whereas CYP4A inhibition attenuated these effects. In vitro TAM polarization away from the M2 phenotype induced by CYP4A inhibition decreased VEGFR1
myeloid cell migration and fibronectin expression, accompanied with downregulation of STAT3 signaling. Conversely, overexpression of CYP4A or exogenous addition of 20-hydroxyeicosatetraenoic acid promoted M2 polarization and cytokine production of macrophages and thereby enhanced migration of VEGFR1
myeloid cells, which were reversed by siRNA or pharmacological inhibition of STAT3. Importantly, a combined blocking M2 macrophage-derived factors TGF-β, VEGF and SDF-1 abolished VEGFR1
myeloid cell migration and fibroblast activation induced by CYP4A. In summary, CYP4A in TAMs is crucial for lung pre-metastatic niche formation and metastasis, and may serve as a potential therapeutic target in human cancer.
High-temperature annealing of gallium arsenide in vacuum causes excess evaporation of arsenic, with accumulation of gallium as liquid droplets on the surface. Using real-time in situ surface electron ...microscopy, we found that these droplets spontaneously run across the crystal surface. Running droplets have been seen in many systems, but they typically require special surface preparation or gradient forces. In contrast, we show that noncongruent evaporation automatically provides a driving force for running droplets. The motion is predicted and observed to slow and stop near a characteristic temperature, with the speed increasing both below and above this temperature. The same behavior is expected to occur during the evaporation of similar III-V semiconductors such as indium arsenide.
► Effect of substrate structure on TFC FO hollow fiber performance was investigated. ► A substrate with <300
kDa MWCO is preferred to obtain a good semipermeable skin. ► It may not be appropriate to ...use DI water to evaluate FO membrane. ► Surface structure facing feed is critical as it is linked with FO membrane fouling.
Forward osmosis (FO) membranes have gained increasingly attention due to their potential advantages for various FO-based wastewater treatment, seawater desalination and power generation. In the present study, an attempt was made to systematically investigate the effects of substrate structure on the formation of the selective layer in a two-step preparation – a phase inversion for a hollow fiber substrate followed by interfacial polymerization for the ultra-thin selective layer, and on the FO performance in non-ideal situations, i.e., the feed stream contains foulants.
Experimental results revealed that the substrate surface structure is very important for fabricating a RO-like thin film. A substrate with <300
kDa MWCO is preferred to obtain a good semipermeable skin based on current study. It may not be appropriate to use DI water and a low concentration draw solution (i.e., an ideal situation) to evaluate the FO membrane, as the water permeation through the RO-like skin is the rate-determining step, and the effect of the substrate structure cannot be fully reflected in this ideal situation. In addition, the surface structure of the FO membrane facing the feed is critical as it is directly associated with the tendency of FO membrane fouling, and a relatively dense membrane substrate surface is desirable in the membrane orientation of active layer facing draw solution. An ideal FO membrane should also possess anti-fouling capability or less fouling propensity in addition to high water permeability, low salt permeability and minimized structural parameter.
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