Origin of the Sinai-Negev erg, Egypt and Israel: mineralogical and geochemical evidence for the importance of the Nile and sea level history

The Sinai-Negev erg occupies an area of 13,000 km2 in the deserts of Egypt and Israel. Aeolian sand of this erg has been proposed to be derived from the Nile Delta, but empirical data supporting this view are lacking. An alternative source sediment is sand from the large Wadi El Arish drainage system in central and northern Sinai. Mineralogy of the Negev and Sinai dunes shows that they are high in quartz, with much smaller amounts of K-feldspar and plagioclase. Both Nile Delta sands and Sinai wadi sands, upstream of the dunes, also have high amounts of quartz relative to K-feldspar and plagioclase. However, Sinai wadi sands have abundant calcite, whereas Nile Delta sands have little or no calcite. Overall, the mineralogical data suggest that the dunes are derived dominantly from the Nile Delta, with Sinai wadi sands being a minor contributor. Geochemical data that proxy for both the light mineral fraction (SiO2/10-Al2O3 + Na2O + K2O-CaO) and heavy mineral fraction (Fe2O3-MgO-TiO2) also indicate a dominant Nile Delta source for the dunes. Thus, we report here the first empirical evidence that the Sinai-Negev dunes are derived dominantly from the Nile Delta. Linkage of the Sinai-Negev erg to the Nile Delta as a source is consistent with the distribution of OSL ages of Negev dunes in recent studies. Stratigraphic studies show that during the Last Glacial period, when dune incursions in the Sinai-Negev erg began, what is now the Nile Delta area was characterized by a broad, sandy, minimally vegetated plain, with seasonally dry anastomosing channels. Such conditions were ideal for providing a ready source of sand for aeolian transport under what were probably much stronger glacial-age winds. With the post-glacial rise in sea level, the Nile River began to aggrade. Post-glacial sedimentation has been dominated by fine-grained silts and clays. Thus, sea level, along with favorable climatic conditions, emerges as a major influence on the timing of dune activity in the Sinai-Negev erg, through its control on the supply of sand from the Nile Delta. The mineralogy of the Sinai-Negev dunes is also consistent with a proposed hypothesis that these sediments are an important source of loess in Israel

The histone deacetylase inhibitor, romidepsin, as a potential treatment for pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive disease that usually affects elderly people. It has a poor prognosis and there are limited therapies. Since epigenetic alterations are associated with IPF, histone deacetylase (HDAC) inhibitors offer a novel therapeutic strategy to address the unmet medical need. This study investigated the potential of romidepsin, an FDA-approved HDAC inhibitor, as an anti-fibrotic treatment and evaluated biomarkers of target engagement that may have utility in future clinical trials. The anti-fibrotic effects of romidepsin were evaluated both in vitro and in vivo together with any harmful effect on alveolar type II cells (ATII). Bronchoalveolar lavage fluid (BALF) from IPF or control donors was analyzed for the presence of lysyl oxidase (LOX). In parallel with an increase in histone acetylation, romidepsin potently inhibited fibroblast proliferation, myofibroblast differentiation and LOX expression. ATII cell numbers and their lamellar bodies were unaffected. In vivo, romidepsin inhibited bleomycin-induced pulmonary fibrosis in association with suppression of LOX expression. LOX was significantly elevated in BALF of IPF patients compared to controls. These data show the anti-fibrotic effects of romidepsin, supporting its potential use as novel treatment for IPF with LOX as a companion biomarker for evaluation of early on-target effects

The role of inflammation in anxiety and depression in the European U-BIOPRED asthma cohorts

BACKGROUND: Growing evidence indicates high comorbid anxiety and depression in patients with asthma. However, the mechanisms underlying this comorbid condition remain unclear. The aim of this study was to investigate the role of inflammation in comorbid anxiety and depression in three asthma patient cohorts of the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) project. METHODS: U-BIOPRED was conducted by a European Union consortium of 16 academic institutions in 11 European countries. A subset dataset from subjects with valid anxiety and depression measures and a large blood biomarker dataset were analysed, including 198 non-smoking patients with severe asthma (SAn), 65 smoking patients with severe asthma (SAs), 61 non-smoking patients with mild-to-moderate asthma (MMA), and 20 healthy non-smokers (HC). The Hospital Anxiety and Depression Scale was used to measure anxiety and depression and a series of inflammatory markers were analysed by the SomaScan v3 platform (SomaLogic, Boulder, Colo). ANOVA and the Kruskal-Wallis test were used for multiple-group comparisons as appropriate. RESULTS: There were significant group effects on anxiety and depression among the four cohort groups (p < 0.05). Anxiety and depression of SAn and SAs groups were significantly higher than that of MMA and HC groups (p < 0.05. There were significant differences in serum IL6, MCP1, CCL18, CCL17, IL8, and Eotaxin among the four groups (p < 0.05). Depression was significantly associated with IL6, MCP1, CCL18 level, and CCL17; whereas anxiety was associated with CCL17 only (p < 0.05). CONCLUSIONS: The current study suggests that severe asthma patients are associated with higher levels of anxiety and depression, and inflammatory responses may underlie this comorbid condition

Hygiene inspections on passenger ships in Europe - an overview

<p>Abstract</p> <p>Background</p> <p>Hygiene inspections on passenger ships are important for the prevention of communicable diseases. The European Union (EU) countries conduct hygiene inspections on passenger ships in order to ensure that appropriate measures have been taken to eliminate potential sources of contamination which could lead to the spread of communicable diseases. This study was implemented within the framework of the EU SHIPSAN project and it investigates the legislation applied and practices of hygiene inspections of passenger ships in the EU Member States (MS) and European Free Trade Association countries.</p> <p>Methods</p> <p>Two questionnaires were composed and disseminated to 28 countries. A total of 92 questionnaires were completed by competent authorities responsible for hygiene inspections (n = 48) and the creation of legislation (n = 44); response rates were 96%, and 75.9%, respectively.</p> <p>Results</p> <p>Out of the 48 responding authorities responsible for hygiene inspections, a routine programme was used by 19 (39.6%) of these to conduct inspections of ships on national voyages and by 26 (54.2%) for ships on international voyages. Standardised inspection forms are used by 59.1% of the authorities. A scoring inspection system is applied by five (11.6%) of the 43 responding authorities. Environmental sampling is conducted by 84.1% of the authorities (37 out of 44). The inspection results are collected and analysed by 54.5% (24 out of 44) of the authorities, while 9 authorities (20.5%) declared that they publish the results. Inspections are conducted during outbreak investigations by 75% and 70.8% of the authorities, on ships on national and international voyages, respectively. A total of 31 (64.6%) and 39 (81.3%) authorities conducted inspections during complaint investigations on ships on international and on national voyages, respectively. Port-to-port communication between the national port authorities was reported by 35.4% (17 out of 48) of the responding authorities and 20.8% (10 out of 48) of the port authorities of other countries.</p> <p>Conclusion</p> <p>This study revealed a diversity of approaches and practices in the conduct of inspections, differences in the qualifications/knowledge/experience of inspectors, the legislation applied during inspections, and the lack of communication and training among many EU countries. An integrated European inspection programme involving competent expert inspectors in each EU Member States and special training for ship hygiene delivered to crew members and inspectors would help to minimize the risk of communicable diseases. Common inspection tools at a European level for hygiene inspection practices and port-to-port communication are needed.</p

The Emergence and Development of Association Football: Influential Sociocultural Factors in Victorian Birmingham

This article explores the interdependent, complex sociocultural factors that facilitated the emergence and diffusion of football in Birmingham. The focus is the development of football in the city, against the backdrop of the numerous social changes in Victorian Birmingham. The aim is to fill a gap in the existing literature which seemingly overlooked Birmingham as a significant footballing centre, and the ‘ordinary and everyday’ aspects of the game’s early progression. Among other aspects, particular heed is paid to the working classes’ involvement in football, as previous literature has often focused on the middle classes and their influence on and participation in organized sport. As the agency of the working classes along with their mass participation and central role in the game’s development is unfolded, it is argued that far from being passive cultural beings, the working classes, from the beginnings, actively negotiated the development of their own emergent football culture

Stratification of asthma phenotypes by airway proteomic signatures

© 2019 Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies

Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation

Background: Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) to asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthmatic patients is unclear. Objective: We sought to explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthmatic patients. Methods: An IL-6TS gene signature obtained from air-liquid interface cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R was used to stratify lung epithelial transcriptomic data (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes [U-BIOPRED] cohorts) by means of hierarchical clustering. IL-6TS-specific protein markers were used to stratify sputum biomarker data (Wessex cohort). Molecular phenotyping was based on transcriptional profiling of epithelial brushings, pathway analysis, and immunohistochemical analysis of bronchial biopsy specimens. Results: Activation of IL-6TS in air-liquid interface cultures reduced epithelial integrity and induced a specific gene signature enriched in genes associated with airway remodeling. The IL-6TS signature identified a subset of patients with IL-6TS-high asthma with increased epithelial expression of IL-6TS-inducible genes in the absence of systemic inflammation. The IL-6TS-high subset had an overrepresentation of frequent exacerbators, blood eosinophilia, and submucosal infiltration of T cells and macrophages. In bronchial brushings Toll-like receptor pathway genes were upregulated, whereas expression of cell junction genes was reduced. Sputum sIL-6R and IL-6 levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, matrix metalloproteinase 3, macrophage inflammatory protein 1 beta, IL-8, and IL-1 beta. Conclusions: Local lung epithelial IL-6TS activation in the absence of type 2 airway inflammation defines a novel subset of asthmatic patients and might drive airway inflammation and epithelial dysfunction in these patients.Peer reviewe

Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation

Rationale Asthma phenotyping requires novel biomarker discovery. Objectives To identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, COPD subjects and healthy controls (HCs). Methods An antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HCs in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a 2-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED. Results In U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HCs. 10 proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, TNF receptor superfamily member 11a, transforming growth factor-β and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, high-sensitivity C-reactive protein and body mass index, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation. Conclusions The plasma proteomic panel revealed previously unexplored yet potentially useful Type-2independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA