479 research outputs found

    Droplet impact onto moving liquids

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    From rain drops landing on the ocean to inkjet printing, the impact of droplets onto moving liquid surfaces is a ubiquitous process in nature and in industry. A rich range of phenomena can arise. The behaviour depends on the inertia, the properties of the drops and the relative speeds in the impact zone. While the result ranges from tranquil coalescence to violent splashing, intermediate regimes also occur, including partial and complete bouncing and even 'surfing' of the droplet. These regimes are determined by the ratio of the drop and surface velocities and the liquid properties. A regime diagram can be constructed in which distinct dynamical regimes are clearly identified.This project was supported by the EPSRC (grant EP/H018913/1), the John Fell Oxford University Press Research Fund, and the Royal Society (through a University Research Fellowship and a Research Grant)

    Contribution of tumour and immune cells to PD-L1 expression as a predictive biomarker in metastatic triple-negative breast cancer: exploratory analysis from KEYNOTE-119

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    Pembrolizumab; Triple‐negative breast cancerPembrolizumab; Cáncer de mama triple negativoPembrolizumab; Càncer de mama triple negatiuThe efficacy of pembrolizumab monotherapy versus chemotherapy increased with increasing programmed death ligand 1 (PD-L1) expression, as quantified by combined positive score (CPS; PD-L1 expression on both tumour cells and immune cells) in patients with previously treated metastatic triple-negative breast cancer (mTNBC) in the phase 3 KEYNOTE-119 study. This exploratory analysis was conducted to determine whether the expression of PD-L1 on tumour cells contributes to the predictive value of PD-L1 CPS in mTNBC. PD-L1 expression in tumour samples was assessed using PD-L1 IHC 22C3 pharmDx and quantified using both CPS and tumour proportion score (TPS; PD-L1 expression on tumour cells alone). Calculated immune cell density (CID) was defined as CPS minus TPS. The ability of each scoring method (CPS, TPS, and CID) to predict clinical outcomes with pembrolizumab was evaluated. With pembrolizumab, the area under the receiver operating characteristic curve was 0.69 (95% CI = 0.58–0.80) for CPS, 0.55 (95% CI = 0.46–0.64) for TPS, and 0.67 (95% CI = 0.56–0.77) for CID. After correction for cutoff prevalence, CPS performed as well as, if not better than, CID with respect to predicting objective response rate, progression-free survival, and overall survival. Data from this exploratory analysis suggest that, although PD-L1 expression on immune cells alone is predictive of response to programmed death 1 blockade in mTNBC, adding tumour PD-L1 expression assessment (i.e. CPS, which combines immune cell and tumour cell PD-L1 expression) may improve prediction. PD-L1 CPS thus remains an effective and broadly applicable uniform scoring system for enriching response to programmed death 1 blockade with pembrolizumab in mTNBC as well as other tumour types

    De Novo Assembly of the Dirofilaria immitis Genome by Long-Read Nanopore-Based Sequencing Technology on an Adult Worm from a Canine Cardiopulmonary Dirofilariosis Case

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    Dirofilaria immitis is a zoonotic parasitic nematode that infects domestic and wild canids, among its vertebrate hosts. The genetic analysis of D. immitis nowadays transcends the need for genetic taxonomy of nematodes, such as the study of resistance to macrocyclic lactone. We expanded the use of long-read nanopore-based sequencing technology on nematodes by performing genomic de novo assembly of a D. immitis specimen retrieved from a canine cardiopulmonary dirofilariasis case using the ONT MinION platform, followed by the study of macrocyclic lactone resistance. The assembled genome of D. immitis consists of 110 contigs with an N50 of 3687191. The genome size is 87899012 and contains a total of 9741 proteins; 6 ribosomal RNAs, with three belonging to the small subunit (18S) and three to the large subunit (28S); and 73 tRNAs. Subsequent analysis of six loci previously characterized as being associated to macrocyclic lactone resistance selection pressure showed that four have a genotype associated with either some loss of efficacy or the resistance phenotype. Considering the zoonotic potential of D. immitis, the identification of a resistant parasite alerts for the overuse of macrocyclic lactone in the region, which poses a potential risk to both veterinary and human public health. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Funding: This work was supported by national funds through the Fundação para a CiĂȘncia e Tec-nologia (FCT, Portuguese Foundation for Science and Technology) under projects UIDB/04750/2020, LA/P/0064/2020, UIDB/CVT/00772/2020, and LA/P/0059/2020

    The Cosmic Lens All-Sky Survey: statistical strong lensing, cosmological parameters, and global properties of galaxy populations

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    Extensive analyses of statistical strong gravitational lensing are performed based on the final Cosmic Lens All Sky Survey (CLASS) well-defined statistical sample of flat spectrum radio sources and current estimates of galaxy luminosity functions per morphological type. The analyses are done under the assumption that galactic lenses are well-approximated by singular isothermal ellipsoids and early-type galaxies evolved passively since redshift z∌1z \sim 1. Depending on how the late-type galaxy population is treated (i.e., whether its characteristic velocity dispersion is constrained or not), we find for a flat universe with a cosmological constant that the present matter fraction of the present critical density Ωm=0.31−0.14+0.27\Omega_{\rm m} = 0.31^{+0.27}_{-0.14} (68%) for the unconstrained case or 0.40−0.16+0.280.40^{+0.28}_{-0.16} (68%) for the constrained case, with an additional systematic uncertainty of ≈0.11\approx 0.11 arising from the present uncertainty in the distribution of CLASS sources in redshift and flux density. For a flat universe with a constant equation of state for dark energy w = pxp_x(pressure)/ρx\rho_x(energy density), we find that w<−0.55−0.11+0.18w < -0.55^{+0.18}_{-0.11} (68%) for the unconstrained case or w<−0.41−0.16+0.28w < -0.41^{+0.28}_{-0.16} (68%) for the constrained case. For the equal frequencies of oblates and prolates, we find that σ∗(e)=198−18+22\sigma_{*}^{(e)} = 198^{+22}_{-18} km s−1^{-1} (68%) for a `steep' α(e)=−1\alpha^{(e)}=-1 or σ∗(e)=181−15+18\sigma_{*}^{(e)} = 181^{+18}_{-15} km s−1^{-1} (68%) for a `shallow' α(e)=−0.54\alpha^{(e)}=-0.54. Finally, from the relative frequencies of doubly-imaged sources and quadruply-imaged sources, we find that a mean projected mass ellipticity of early-type galaxies ϔˉmass=0.42\bar{\epsilon}_{\rm mass} = 0.42 with a 68% lower limit of 0.28. (Abridged)Comment: 31 pages, 12figures, 6 tables, to appear in MNRAS (referee comments incorporated, a section on future prospects added

    Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial

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    Margetuximab; Breast cancer; Overall survivalMargetuximab; Cáncer de mama; Supervivencia globalMargetuximab; Càncer de mama; Supervivùncia globalFinal overall survival (OS) in SOPHIA (ClinicalTrials.gov identifier: NCT02492711), a study of margetuximab versus trastuzumab, both with chemotherapy, in patients with previously treated human epidermal growth factor receptor 2–positive advanced breast cancer, is reported with updated safety. Overall, 536 patients in the intention-to-treat population were randomly assigned to margetuximab (15 mg/kg intravenously once every 3 weeks; n = 266) plus chemotherapy or trastuzumab (6 mg/kg intravenously once every 3 weeks after a loading dose of 8 mg/kg; n = 270) plus chemotherapy. Primary end points were progression-free survival, previously reported, and OS. Final OS analysis was triggered by 385 prespecified events. The median OS was 21.6 months (95% CI, 18.89 to 25.07) with margetuximab versus 21.9 months (95% CI, 18.69 to 24.18) with trastuzumab (hazard ratio [HR], 0.95; 95% CI, 0.77 to 1.17; P = .620). Preplanned, exploratory analysis of CD16A genotyping suggested a possible improvement in OS for margetuximab in CD16A-158FF patients versus trastuzumab (median OS, 23.6 v 19.2 months; HR, 0.72; 95% CI, 0.52 to 1.00) and a possible improvement in OS for trastuzumab in CD16A-158VV patients versus margetuximab (median OS, 31.1 v 22.0 months; HR, 1.77; 95% CI, 1.01 to 3.12). Margetuximab safety was comparable with trastuzumab. Final overall OS analysis did not demonstrate margetuximab advantage over trastuzumab. Margetuximab studies in patients with human epidermal growth factor receptor 2–positive breast cancer with different CD16A allelic variants are warranted

    Ab-initio study of the stability and electronic properties of wurtzite and zinc-blende BeS nanowires

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    In this work we study the structural stability and electronic properties of the Beryllium sulphide nanowires (NWs) in both zinc blende (ZB) and wurtzite (WZ) phases with triangle and hexagonal cross section, using first principle calculations within plane-wave pseudopotential method. A phenomenological model is used to explain the role of dangling bonds in the stability of the NWs. In contrast to the bulk phase, ZB-NWs with diameter less than 133.3 (angstrom) are found to be less favorable over WZ-NWs, in which the surface dangling bonds (DBs) on the NW facets play an important role to stabilize the NWs. Furthermore, both ZB and WZ NWs are predicted to be semiconductor and the values of the band gaps are dependent on the surface DBs as well as the size and shape of NWs. Finally, we performed atom projected density-of states (PDOSs) analysis by calculating the localized density of states on the surface atoms, as well as on the core and edge atoms.Comment: 9 Pages, 6 Figure

    Recruiting participants for interventions to prevent the onset of depressive disorders: Possibile ways to increase participation rates

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    Background: Although indicated prevention of depression is available for about 80% of the Dutch population at little or no cost, only a small proportion of those with subthreshold depression make use of these services. Methods: A narrative review is conducted of the Dutch preventive services in mental health care, also addressing the problem of low participation rates. We describe possible causes of these low participation rates, which may be related to the participants themselves, the service system, and the communication to the public, and we put forward possible solutions to this problem. Results: There are three main groups of reasons why the participation rates are low: reasons within the participants (e.g., not considering themselves as being at risk; thinking the interventions are not effective; or being unwilling to participate because of the stigma associated with depression); reasons within the health care system; and reasons associated with the communication about the preventive services. Possible solutions to increasing the participation rate include organizing mass media campaigns, developing internet-based preventive interventions, adapting preventive interventions to the needs of specific subpopulations, positioning the services in primary care, integrating the interventions in community-wide interventions, and systematically screening high-risk groups for potential participants. Discussion: Prevention could play an important role in public mental health in reducing the enormous burden of depression. However, before this can be realized more research is needed to explore why participation rates are low and how these rates can be improved

    Testing the dark energy with gravitational lensing statistics

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    We study the redshift distribution of two samples of early-type gravitational lenses, extracted from a larger collection of 122 systems, to constrain the cosmological constant in the LCDM model and the parameters of a set of alternative dark energy models (XCDM, Dvali-Gabadadze-Porrati and Ricci dark energy models), under a spatially flat universe. The likelihood is maximized for ΩΛ=0.70±0.09\Omega_\Lambda= 0.70 \pm 0.09 when considering the sample excluding the SLACS systems (known to be biased towards large image-separation lenses) and no-evolution, and ΩΛ=0.81±0.05\Omega_\Lambda= 0.81\pm 0.05 when limiting to gravitational lenses with image separation larger than 2" and no-evolution. In both cases, results accounting for galaxy evolution are consistent within 1σ\sigma. The present test supports the accelerated expansion, by excluding the null-hypothesis (i.e., ΩΛ=0\Omega_\Lambda = 0 ) at more than 4σ\sigma, regardless of the chosen sample and assumptions on the galaxy evolution. A comparison between competitive world models is performed by means of the Bayesian information criterion. This shows that the simplest cosmological constant model - that has only one free parameter - is still preferred by the available data on the redshift distribution of gravitational lenses. We perform an analysis of the possible systematic effects, finding that the systematic errors due to sample incompleteness, galaxy evolution and model uncertainties approximately equal the statistical errors, with present-day data. We find that the largest sources of systemic errors are the dynamical normalization and the high-velocity cut-off factor, followed by the faint-end slope of the velocity dispersion function.Comment: 14 pages, 10 figures, accepted for publication in The Astrophysical Journal. Updated to match print versio
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