Capital structure and its determinants in the United Kingdom – a decompositional analysis

Prior research on capital structure by Rajan and Zingales (1995) suggests that the level of gearing in UK companies is positively related to size and tangibility, and negatively correlated with profitability and the level of growth opportunities. However, as argued by Harris and Raviv (1991), 'The interpretation of results must be tempered by an awareness of the difficulties involved in measuring both leverage and the explanatory variables of interest'. In this study the focus is on the difficulties of measuring gearing, and the sensitivity of Rajan and Zingales' results to variations in gearing measures are tested. Based on an analysis of the capital structure of 822 UK companies, Rajan and Zingales' results are found to be highly definitional-dependent. The determinants of gearing appear to vary significantly, depending upon which component of debt is being analysed. In particular, significant differences are found in the determinants of long- and short-term forms of debt. Given that trade credit and equivalent, on average, accounts for more than 62% of total debt, the results are particularly sensitive to whether such debt is included in the gearing measure. It is argued, therefore, that analysis of capital structure is incomplete without a detailed examination of all forms of corporate debt

The Bristol method: How to reduce traffic and its impacts

THE BRISTOL METHODThe Bristol Method is a knowledge-transfer programme aimed at helping people in other cities understand and apply the lessons that Bristol has learned in becoming a more sustainable city, not just in 2015 but in the last decade.Each module of the Bristol Method is presented as an easy-to-digest ‘how to’ guide on a particular topic, which use Bristol’s experiences as a case study. The modules contain generic advice and recommendations that each reader can tailor to their own circumstances.This module focusses on the air quality impacts and the traffic reduction interventions which are being used to improve the current situation. In addition to improving air quality, these interventions will help to reduce the other negative impacts of road traffic

The effect of alcohol consumption on the risk of ARDS: a systematic review and meta-analysis

BACKGROUND: To conduct a systematic review and meta-analysis evaluating the association between alcohol consumption and the risk of ARDS in adults. METHODS: Medline, EMBASE and Web of Science were searched to identify observational studies evaluating the association between prior alcohol intake and the occurrence of ARDS among adults, published between 1985 and 2015 and with no language restriction. Reference lists were also screened. Demographic baseline data were extracted independently by two reviewers and random-effects meta-analyses were used to estimate pooled effect sizes with 95% confidence intervals. Subgroup analyses were used to explore heterogeneity. RESULTS: Seventeen observational studies (177,674 people) met the inclusion criteria. Metaanalysis of 13 studies showed that any measure of high relative to low alcohol consumption was associated with a significantly increased risk of ARDS (OR, 1.89; 95% CI, 1.45-2.48; I² = 48%; 13 studies); no evidence of publication bias was seen (P = .150). Sensitivity analyses indicated that this association was attributable primarily to an effect of a history of alcohol abuse (OR, 1.90; 95% CI, 1.40-2.60; 10 studies). Also, subgroup analyses identified that heterogeneity was explained by predisposing condition (trauma, sepsis/septic shock, pneumonia; P = .003). CONCLUSIONS: Chronic high alcohol consumption significantly increases the risk of ARDS. This finding suggests that patients admitted to hospital should be screened for chronic alcohol use

Neurotensin Receptor 1 Is Expressed in Gastrointestinal Stromal Tumors but Not in Interstitial Cells of Cajal

Gastrointestinal stromal tumors (GIST) are thought to derive from the interstitial cells of Cajal (ICC) or an ICC precursor. Oncogenic mutations of the KIT or PDGFRA receptor tyrosine kinases are present in the majority of GIST, leading to ligand-independent activation of the intracellular signal transduction pathways. We previously investigated the gene expression profile in the murine KitK641E GIST model and identified Ntsr1 mRNA, encoding the Neurotensin receptor 1, amongst the upregulated genes. Here we characterized Ntsr1 mRNA and protein expression in the murine KitK641E GIST model and in tissue microarrays of human GIST. Ntsr1 mRNA upregulation in KitK641E animals was confirmed by quantitative PCR. Ntsr1 immunoreactivity was not detected in the Kit positive ICC of WT mice, but was present in the Kit positive hyperplasia of KitK641E mice. In the normal human gut, NTSR1 immunoreactivity was detected in myenteric neurons but not in KIT positive ICC. Two independent tissue microarrays, including a total of 97 GIST, revealed NTSR1 immunoreactivity in all specimens, including the KIT negative GIST with PDGFRA mutation. NTSR1 immunoreactivity exhibited nuclear, cytoplasmic or mixed patterns, which might relate to variable levels of NTSR1 activation. As studies using radio-labeled NTSR1 ligand analogues for whole body tumor imaging and for targeted therapeutic interventions have already been reported, this study opens new perspectives for similar approaches in GIST

Petrophysical, Geochemical, and Hydrological Evidence for Extensive Fracture-Mediated Fluid and Heat Transport in the Alpine Fault's Hanging-Wall Damage Zone

International audienceFault rock assemblages reflect interaction between deformation, stress, temperature, fluid, and chemical regimes on distinct spatial and temporal scales at various positions in the crust. Here we interpret measurements made in the hanging‐wall of the Alpine Fault during the second stage of the Deep Fault Drilling Project (DFDP‐2). We present observational evidence for extensive fracturing and high hanging‐wall hydraulic conductivity (∼10−9 to 10−7 m/s, corresponding to permeability of ∼10−16 to 10−14 m2) extending several hundred meters from the fault's principal slip zone. Mud losses, gas chemistry anomalies, and petrophysical data indicate that a subset of fractures intersected by the borehole are capable of transmitting fluid volumes of several cubic meters on time scales of hours. DFDP‐2 observations and other data suggest that this hydrogeologically active portion of the fault zone in the hanging‐wall is several kilometers wide in the uppermost crust. This finding is consistent with numerical models of earthquake rupture and off‐fault damage. We conclude that the mechanically and hydrogeologically active part of the Alpine Fault is a more dynamic and extensive feature than commonly described in models based on exhumed faults. We propose that the hydrogeologically active damage zone of the Alpine Fault and other large active faults in areas of high topographic relief can be subdivided into an inner zone in which damage is controlled principally by earthquake rupture processes and an outer zone in which damage reflects coseismic shaking, strain accumulation and release on interseismic timescales, and inherited fracturing related to exhumation

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century