Exploring droplet impact near a millimetre-sized hole: comparing a closed pit with an open-ended pore

We investigate drop impact dynamics near both closed pits and open- ended pores experimentally. The resulting impact phenomena differ greatly for a pit or a pore. For the first, we observe three phenomena: a splash, a jet and an air bubble, whose appearance depends on the distance between impact location and pit. Furthermore, we found that splash velocities can reach up to seven times the impact velocity. Drop impact near a pore, however, results solely in splashing. Surprisingly, two distinct and disconnected splashing regimes occur, with a region of plain spreading in-between. For pores, splashes are less pronounced than in the pit case. We state that, for the pit case, the presence of air inside the pit plays a crucial role: it promotes splashing and allows for air bubbles to appear.Comment: 17 pages, 11 figures, 1 supplementary movie, submitted to JF

The effect of six-month oral vitamin K supplementation on calcification propensity time in individuals with type 2 diabetes mellitus: A post hoc analysis of a randomized, double-blind, placebo-controlled trial

Background and aims: Experimental studies suggested that vitamin K supplementation may retard arterial calcification. Recently, serum calcification propensity time (T50) has been suggested as a functional biomarker for arterial wall calcification propensity. In this post-hoc analysis of a clinical trial, we evaluated the effect of six-month oral vitamin K supplementation on T50 and assessed the correlation between T50 and imaging arterial calcification parameters in people with type 2 diabetes (T2DM). Methods: This double-blind, randomized, placebo-controlled trial included 68 participants (age = 69 ± 8 years, 76% male) with T2DM. Participants were assigned to menaquinone-7 (360 μg/day; n = 35) or placebo (n = 33). T50 was measured via nephelometry in serum collected at baseline, three and six months. Arterial calcification was measured at baseline and six months via 18F–Na PET-CT and conventional CT using Target-to-Background ratio (TBR) and Agatston score. Longitudinal analysis of covariance adjusted for baseline T50 was used to study the treatment effect. Spearman's correlation was used to assess the correlation between T50 and imaging calcification parameters. Results: Median baseline T50 was similar in the vitamin K (350 [321–394] minutes) and placebo groups (363 [320–398]). There was no significant difference in T50 between treatment arms over time (ẞ = 1.00, 95%C.I. = 0.94–1.07, p = 0.982). The correlation coefficient of T50 with TBR and Agatston score at baseline were −0.185 (p = 0.156) and −0.121 (p = 0.358), respectively. Conclusions: No effect of vitamin K supplementation on T50 was observed in T2DM. Moreover, T50 did not correlate with TBR and Agatston score. Further research on vitamin K in arterial calcification and on the validity of T50 as arterial calcification marker is warranted

Sub-electron Charge Relaxation via 2D Hopping Conductors

We have extended Monte Carlo simulations of hopping transport in completely disordered 2D conductors to the process of external charge relaxation. In this situation, a conductor of area $L \times W$ shunts an external capacitor $C$ with initial charge $Q_i$. At low temperatures, the charge relaxation process stops at some "residual" charge value corresponding to the effective threshold of the Coulomb blockade of hopping. We have calculated the r.m.s$.$ value $Q_R$ of the residual charge for a statistical ensemble of capacitor-shunting conductors with random distribution of localized sites in space and energy and random $Q_i$, as a function of macroscopic parameters of the system. Rather unexpectedly, $Q_{R}$ has turned out to depend only on some parameter combination: $X_0 \equiv L W \nu_0 e^2/C$ for negligible Coulomb interaction and $X_{\chi} \equiv LW \kappa^2/C^{2}$ for substantial interaction. (Here $\nu_0$ is the seed density of localized states, while $\kappa$ is the dielectric constant.) For sufficiently large conductors, both functions $Q_{R}/e =F(X)$ follow the power law $F(X)=DX^{-\beta}$, but with different exponents: $\beta = 0.41 \pm 0.01$ for negligible and $\beta = 0.28 \pm 0.01$ for significant Coulomb interaction. We have been able to derive this law analytically for the former (most practical) case, and also explain the scaling (but not the exact value of the exponent) for the latter case. In conclusion, we discuss possible applications of the sub-electron charge transfer for "grounding" random background charge in single-electron devices.Comment: 12 pages, 5 figures. In addition to fixing minor typos and updating references, the discussion has been changed and expande

Study Protocol PROMETHEUS:Prospective Multicenter Study to Evaluate the Correlation Between Safety Margin and Local Recurrence After Thermal Ablation Using Image Co-registration in Patients with Hepatocellular Carcinoma

Purpose: The primary objective is to determine the minimal ablation margin required to achieve a local recurrence rate of 18 years with Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma (or B with a maximum of two lesions < 5 cm each) are eligible. Patients will undergo dual-phase contrast-enhanced computed tomography directly before and after ablation. Ablation margins will be quantitatively assessed using co-registration software, blinding assessors (i.e. two experienced radiologists) for outcome. Presence and location of recurrence are evaluated independently on follow-up scans by two other experienced radiologists, blinded for the quantitative margin analysis. A sample size of 189 tumors (~ 145 patients) is required to show with 80% power that the risk of local recurrence is confidently below 10%. A two-sided binomial z-test will be used to test the null hypothesis that the local recurrence rate is ≥ 10% for patients with a minimal ablation margin ≥ 2 mm. Logistic regression will be used to find the relationship between minimal ablation margins and local recurrence. Kaplan–Meier estimates are used to assess local and overall recurrence, disease-free and overall survival. Discussion: It is expected that this study will result in a clear understanding of the correlation between ablation margins and local recurrence. Using co-registration software in future patients undergoing ablation for hepatocellular carcinoma may improve intraprocedural evaluation of technical success. Trial registration The Netherlands Trial Register (NL9713), https://www.trialregister.nl/trial/9713

The association between skeletal muscle measures and chemotherapy-induced toxicity in non-small cell lung cancer patients

BACKGROUND: Chemotherapy-induced toxicities frequently occur in non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. Low skeletal muscle mass (SMM) has been associated with a higher incidence of toxicities for several types of cancers and cytostatics. The aim of this study was to evaluate the association between skeletal muscle measures and chemotherapy-induced toxicity in a large cohort of NSCLC patients. METHODS: A multicentre prospective follow-up study (PGxLUNG, NTR number NL5373610015) in NSCLC patients was conducted. Included were patients diagnosed with NSCLC (stage II-IV) treated with first-line platinum-based (cisplatin or carboplatin) chemotherapy of whom pretreatment imaging was available. Skeletal muscle area (SMA) segmentation was performed on abdominal imaging at the level of the third lumbar vertebra (L3). SMA at the level of L3 was corrected for squared height (m2 ) to yield the lumbar skeletal muscle mass index (LSMI). Skeletal muscle density (SMD) was calculated as the mean Hounsfield Unit (HU) of the segmented SMA. SMM and SMD were categorized as low, intermediate, and high, based on LSMI and mean HU tertiles, respectively. Chemotherapy-induced toxicity was scored using CTCAE v4.03 and categorized into haematological (anaemia, leukocytopenia, neutropenia, and thrombocytopenia), non-haematological (nephrotoxicity, neurotoxicity, and esophagitis), and dose-limiting toxicity (DLT) (treatment switch, delay, de-escalation, discontinuation, or hospitalization). The relationship between SMM, SMD, and toxicities was assessed with logistic regression modelling taking into account potential confounders like gender and body mass index (BMI). RESULTS: In total, 297 patients (male n = 167, median age 64 years) were included. Haematological toxicity grade 3/4 was experienced in 36.6% (n = 108) of the patients, 24.6% (n = 73) experienced any non-haematological toxicity grade ≥2, and 55.6% (n = 165) any DLT. Multivariate logistic regression analysis showed that low SMM (ORadj 2.41, 95% CI 1.31-4.45, P = 0.005) and age at diagnosis >65 years (ORadj 1.76, 95% CI 1.07-2.90, P = 0.025) were statistically significantly associated with overall haematological toxicity grade 3/4. No statistically significant associations were found between low SMM or low SMD and non-haematological toxicities. Low SMM (ORadj 2.23, 95% CI 1.23-4.04, P = 0.008) and high SMD (ORadj 0.41, 95% CI 0.23-0.74, P = 0.003) were statistically significantly associated with a higher respectively lower risk of DLT. CONCLUSIONS: Non-small cell lung cancer patients with pretreatment low SMM are at significant higher risk for haematological toxicities grade 3/4 and DLT. NSCLC patients with high SMD are at significant lower risk for DLT. Further studies should be aimed to investigate whether platinum dosing based on skeletal muscle measurements and/or improvement of pretreatment SMM/SMD could reduce the risk of toxicity without compromising efficacy

An Integrated Research Infrastructure for Validating Cyber-Physical Energy Systems

Renewables are key enablers in the plight to reduce greenhouse gas emissions and cope with anthropogenic global warming. The intermittent nature and limited storage capabilities of renewables culminate in new challenges that power system operators have to deal with in order to regulate power quality and ensure security of supply. At the same time, the increased availability of advanced automation and communication technologies provides new opportunities for the derivation of intelligent solutions to tackle the challenges. Previous work has shown various new methods of operating highly interconnected power grids, and their corresponding components, in a more effective way. As a consequence of these developments, the traditional power system is being transformed into a cyber-physical energy system, a smart grid. Previous and ongoing research have tended to mainly focus on how specific aspects of smart grids can be validated, but until there exists no integrated approach for the analysis and evaluation of complex cyber-physical systems configurations. This paper introduces integrated research infrastructure that provides methods and tools for validating smart grid systems in a holistic, cyber-physical manner. The corresponding concepts are currently being developed further in the European project ERIGrid.Comment: 8th International Conference on Industrial Applications of Holonic and Multi-Agent Systems (HoloMAS 2017

A Numerical Study of Coulomb Interaction Effects on 2D Hopping Transport

We have extended our supercomputer-enabled Monte Carlo simulations of hopping transport in completely disordered 2D conductors to the case of substantial electron-electron Coulomb interaction. Such interaction may not only suppress the average value of hopping current, but also affect its fluctuations rather substantially. In particular, the spectral density $S_I (f)$ of current fluctuations exhibits, at sufficiently low frequencies, a $1/f$-like increase which approximately follows the Hooge scaling, even at vanishing temperature. At higher $f$, there is a crossover to a broad range of frequencies in which $S_I (f)$ is nearly constant, hence allowing characterization of the current noise by the effective Fano factor F\equiv S_I(f)/2e \left. For sufficiently large conductor samples and low temperatures, the Fano factor is suppressed below the Schottky value (F=1), scaling with the length $L$ of the conductor as $F = (L_c / L)^{\alpha}$. The exponent $\alpha$ is significantly affected by the Coulomb interaction effects, changing from $\alpha = 0.76 \pm 0.08$ when such effects are negligible to virtually unity when they are substantial. The scaling parameter $L_c$, interpreted as the average percolation cluster length along the electric field direction, scales as $L_c \propto E^{-(0.98 \pm 0.08)}$ when Coulomb interaction effects are negligible and $L_c \propto E^{-(1.26 \pm 0.15)}$ when such effects are substantial, in good agreement with estimates based on the theory of directed percolation.Comment: 19 pages, 7 figures. Fixed minor typos and updated reference

Endosonography With or Without Confirmatory Mediastinoscopy for Resectable Lung Cancer:A Randomized Clinical Trial

PURPOSE:Resectable non-small-cell lung cancer (NSCLC) with a high probability of mediastinal nodal involvement requires mediastinal staging by endosonography and, in the absence of nodal metastases, confirmatory mediastinoscopy according to current guidelines. However, randomized data regarding immediate lung tumor resection after systematic endosonography versus additional confirmatory mediastinoscopy before resection are lacking.METHODS:Patients with (suspected) resectable NSCLC and an indication for mediastinal staging after negative systematic endosonography were randomly assigned to immediate lung tumor resection or confirmatory mediastinoscopy followed by tumor resection. The primary outcome in this noninferiority trial (noninferiority margin of 8% that previously showed to not compromise survival, Pnoninferior &lt;.0250) was the presence of unforeseen N2 disease after tumor resection with lymph node dissection. Secondary outcomes were 30-day major morbidity and mortality.RESULTS:Between July 17, 2017, and October 5, 2020, 360 patients were randomly assigned, 178 to immediate lung tumor resection (seven dropouts) and 182 to confirmatory mediastinoscopy first (seven dropouts before and six after mediastinoscopy). Mediastinoscopy detected metastases in 8.0% (14/175; 95% CI, 4.8 to 13.0) of patients. Unforeseen N2 rate after immediate resection (8.8%) was noninferior compared with mediastinoscopy first (7.7%) in both intention-to-treat (Δ, 1.03%; UL 95% CIΔ, 7.2%; Pnoninferior =.0144) and per-protocol analyses (Δ, 0.83%; UL 95% CIΔ, 7.3%; Pnoninferior =.0157). Major morbidity and 30-day mortality was 12.9% after immediate resection versus 15.4% after mediastinoscopy first (P =.4940).CONCLUSION:On the basis of our chosen noninferiority margin in the rate of unforeseen N2, confirmatory mediastinoscopy after negative systematic endosonography can be omitted in patients with resectable NSCLC and an indication for mediastinal staging.</p