Three-phase flow analysis of dense nonaqueous phase liquid infiltration in horizontally layered porous media

We considered dense nonaqueous phase liquid (DNAPL) infiltration into a water-unsaturated porous medium that consists of two horizontal layers, of which the top layer has a lower intrinsic permeability than the bottom layer. DNAPL is the intermediate-wetting fluid with respect to the wetting water and the nonwetting air. The layer interface forms a barrier to DNAPL flow, which causes the DNAPL to spread out horizontally just above the interface. An analytical approximation has been developed to estimate the DNAPL pressure and saturation and the horizontal extension of the DNAPL above the layer interface at steady state for low water saturations. The analytical approximation shows that the DNAPL infiltration is determined by five dimensionless numbers: the heterogeneity factor ¿, the capillary pressure parameter ¿, the gravity number N g , the ratio of the capillary and gravity numbers N c /N g , and the critical DNAPL pressure P o c . Its predictions were compared with the results of a numerical three-phase flow simulator for a number of parameter combinations. For most of these combinations the analytical approximation predicts the DNAPL pressure and saturation profiles at the interface adequately. Using the analytical approximation, we carried out a sensitivity study with respect to the maximum horizontal extension of the plume. The extension of the plumes appears to be highly sensitive to variation of the dimensionless numbers P o c , ¿ and

Distribution of tourists within urban heritage destinations: a hot spot/cold spot analysis of TripAdvisor data as support for destination management

The emergence of social media and Web 2.0 has a notable impact upon the tasks of destination managers as these platforms have developed into influential mechanisms affecting tourist behaviour. This paper shows how Destination Management Organizations (DMOs) can reap the benefits of the Web 2.0 revolution as it serves as an important source of user-generated information, bringing novel opportunities for data-driven destination management. To test the applicability of user-generated content for destination management, this paper analyses restaurant reviews from five Flemish art cities which were retrieved from the Web 2.0 platform TripAdvisor. Getis-Ord hot spot analysis revealed spatial clusters of frequently (‘hot spots’) and rarely (‘cold spots’) reviewed restaurants in four out of the five art cities. By comparing these spatial patterns, the digital footprints of tourists were uncovered and discussed with DMO directors. Found patterns appeared to reflect local policies aimed either at concentrating tourism, as in Bruges, the city with the most prominent hot spot, or spreading tourism over time and space as seen in Antwerp and Ghent where less prominent hot spots were present. The visualization proved to be a valuable input when discussing tourism management and fuelled the sharing of knowledge between the destinations

Imatinib in patients with severe COVID-19: a randomised, double-blind, placebo-controlled, clinical trial

Background The major complication of COVID-19 is hypoxaemic respiratory failure from capillary leak and alveolar oedema. Experimental and early clinical data suggest that the tyrosine-kinase inhibitor imatinib reverses pulmonary capillary leak.Methods This randomised, double-blind, placebo-controlled, clinical trial was done at 13 academic and non-academic teaching hospitals in the Netherlands. Hospitalised patients (aged >= 18 years) with COVID-19, as confirmed by an RT-PCR test for SARS-CoV-2, requiring supplemental oxygen to maintain a peripheral oxygen saturation of greater than 94% were eligible. Patients were excluded if they had severe pre-existing pulmonary disease, had pre-existing heart failure, had undergone active treatment of a haematological or non-haematological malignancy in the previous 12 months, had cytopenia, or were receiving concomitant treatment with medication known to strongly interact with imatinib. Patients were randomly assigned (1:1) to receive either oral imatinib, given as a loading dose of 800 mg on day 0 followed by 400 mg daily on days 1-9, or placebo. Randomisation was done with a computer-based clinical data management platform with variable block sizes (containing two, four, or six patients), stratified by study site. The primary outcome was time to discontinuation of mechanical ventilation and supplemental oxygen for more than 48 consecutive hours, while being alive during a 28-day period. Secondary outcomes included safety, mortality at 28 days, and the need for invasive mechanical ventilation. All efficacy and safety analyses were done in all randomised patients who had received at least one dose of study medication (modified intention-to-treat population). This study is registered with the EU Clinical Trials Register (EudraCT 2020-001236-10).Findings Between March 31, 2020, and Jan 4, 2021, 805 patients were screened, of whom 400 were eligible and randomly assigned to the imatinib group (n=204) or the placebo group (n=196). A total of 385 (96%) patients (median age 64 years [IQR 56-73]) received at least one dose of study medication and were included in the modified intention-to-treat population. Time to discontinuation of ventilation and supplemental oxygen for more than 48 h was not significantly different between the two groups (unadjusted hazard ratio [HR] 0.95 [95% CI 0.76-1.20]). At day 28, 15 (8%) of 197 patients had died in the imatinib group compared with 27 (14%) of 188 patients in the placebo group (unadjusted HR 0.51 [0.27-0.95]). After adjusting for baseline imbalances between the two groups (sex, obesity, diabetes, and cardiovascular disease) the HR for mortality was 0.52 (95% CI 0.26-1.05). The HR for mechanical ventilation in the imatinib group compared with the placebo group was 1.07 (0.63-1.80; p=0.81). The median duration of invasive mechanical ventilation was 7 days (IQR 3-13) in the imatinib group compared with 12 days (6-20) in the placebo group (p=0.0080). 91 (46%) of 197 patients in the imatinib group and 82 (44%) of 188 patients in the placebo group had at least one grade 3 or higher adverse event. The safety evaluation revealed no imatinib-associated adverse events.Interpretation The study failed to meet its primary outcome, as imatinib did not reduce the time to discontinuation of ventilation and supplemental oxygen for more than 48 consecutive hours in patients with COVID-19 requiring supplemental oxygen. The observed effects on survival (although attenuated after adjustment for baseline imbalances) and duration of mechanical ventilation suggest that imatinib might confer clinical benefit in hospitalised patients with COVID-19, but further studies are required to validate these findings. Copyright (C) 2021 Elsevier Ltd. All rights reserved.Pathogenesis and treatment of chronic pulmonary disease

Legal Limits on Food Labelling Law: Comparative Analysis of the EU and the USA

The objective of this study is to explore to what extent freedom of expression should protect food businesses against government intervention with corporate communications on food labels. A functional comparative method was used to analyse the objective. It was found that expression on food labels should be considered primarily commercial in nature. In the USA some food labelling regulations are considered inconsistent with the freedom of commercial expression. EU courts seem to uphold government restrictions to commercial expression in all cases, especially when restrictions are based on protection of human health. It can be concluded that food businesses should only be able to claim free speech rights on food labels when it is of importance to the public or consumers

Sovereign Wealth Funds and Socially Responsible Investing: Do’s and Don’ts

A sovereign wealth fund (SWF) is a long-term investment fund owned by the state. The oldest is the Kuwait Investment Corporation, which was established in 1953. However, because most SWFs were established in 2004 or later, SWFs are, generally speaking, a fairly new phenomenon. Depending on the definition, there are currently between 38 and 50 SWFs worldwide. An SWF can exert influence on the behavior of companies through its investment policy. Due to the expanding number of SWFs, host states became concerned that investments by SWFs could be politically motivated. To ensure host states that SWFs have no political motivations, but merely seek profit, the Santiago Principles were established. However, in a time where private investors are pressed to focus more on social values to become ‘socially responsible’, it may seem strange that SWFs are pressured into a model of private behavior with the objective of only maximizing financial and economic values. This article explores the scope of responsibilities of SWFs in terms of social responsible investment (SRI). The article provides a definition of SWFs and examines the concept of SRI and whether SRI is compatible with the Santiago Principles. Part of the study comprises an evaluation of 38 investment funds, which all qualify as SWFs as per the author’s definition. The legal basis (whether an SWF is embedded in a separate legal entity), governance structure (how the management of the fund is regulated, and whether the regulation is laid down in statutes), and objectives of each of the SWFs are examined. Moreover, it is examined which private regulatory regimes were adopted by these SWFs. The UN Principles of Responsible Investment (UN PRI) and the Santiago Principles will be discussed in more depth. Finally, this article discusses whether SWFs, due to their link to the state, should become leaders in the sustainable investment field

'Incorporating the OECD Guidelines in International Investment Agreements: Turning a Soft Law Obligation into Hard Law?

This article has been written as a response to two recent developments. First, as a response to the recent update of the Organisation for Economic Co-operation and Development (OECD) Guidelines on 25 May 2011, which seem to have taken a form based on human rights due diligence. Second, as a response to the resolution by the European Parliament of 6 April 2011 on the future EU international investment policy in which it asks the Commission to include, in all future agreements, a reference to the updated OECD Guidelines. This article examines how human rights due diligence, as enshrined in the OECD Guidelines, could be incorporated in international investment agreements (IIAs). Therefore, the concept of human rights due diligence as introduced in the UN Guiding Principles and the OECD Guidelines was explored. It includes empirical research as to how multinationals (MNEs) currently incorporate the concept of human rights due diligence in their policies in order to facilitate investors and policymakers with the knowledge necessary to give an adequate response to this concept. It continues by providing several options as to how the OECD Guidelines could be incorporated in investment agreements, including the advantages and disadvantages of these options