222 research outputs found

    The Red Sea, Coastal Landscapes, and Hominin Dispersals

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    This chapter provides a critical assessment of environment, landscape and resources in the Red Sea region over the past five million years in relation to archaeological evidence of hominin settlement, and of current hypotheses about the role of the region as a pathway or obstacle to population dispersals between Africa and Asia and the possible significance of coastal colonization. The discussion assesses the impact of factors such as topography and the distribution of resources on land and on the seacoast, taking account of geographical variation and changes in geology, sea levels and palaeoclimate. The merits of northern and southern routes of movement at either end of the Red Sea are compared. All the evidence indicates that there has been no land connection at the southern end since the beginning of the Pliocene period, but that short sea crossings would have been possible at lowest sea-level stands with little or no technical aids. More important than the possibilities of crossing the southern channel is the nature of the resources available in the adjacent coastal zones. There were many climatic episodes wetter than today, and during these periods water draining from the Arabian escarpment provided productive conditions for large mammals and human populations in coastal regions and eastwards into the desert. During drier episodes the coastal region would have provided important refugia both in upland areas and on the emerged shelves exposed by lowered sea level, especially in the southern sector and on both sides of the Red Sea. Marine resources may have offered an added advantage in coastal areas, but evidence for their exploitation is very limited, and their role has been over-exaggerated in hypotheses of coastal colonization

    Histopathological evaluation of thrombus in patients presenting with stent thrombosis. A multicenter European study: a report of the prevention of late stent thrombosis by an interdisciplinary global European effort consortium

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    Background Stent thrombosis (ST) is a rare but serious complication following percutaneous coronary intervention. Analysis of thrombus composition from patients undergoing catheter thrombectomy may provide important insights into the pathological processes leading to thrombus formation. We performed a large-scale multicentre study to evaluate thrombus specimens in patients with ST across Europe. Methods Patients presenting with ST and undergoing thrombus aspiration were eligible for inclusion. Thrombus collection was performed according to a standardized protocol and specimens were analysed histologically at a core laboratory. Serial tissue cross sections were stained with haematoxylin–eosin (H&E), Carstairs and Luna. Immunohistochemistry was performed to identify leukocyte subsets, prothrombotic neutrophil extracellular traps (NETs), erythrocytes, platelets, and fibrinogen. Results Overall 253 thrombus specimens were analysed; 79 (31.2%) from patients presenting with early ST, 174 (68.8%) from late ST; 79 (31.2%) were from bare metal stents, 166 (65.6%) from drug-eluting stents, 8 (3.2%) were from stents of unknown type. Thrombus specimens displayed heterogeneous morphology with platelet-rich thrombus and fibrin/fibrinogen fragments most abundant; mean platelet coverage was 57% of thrombus area. Leukocyte infiltrations were hallmarks of both early and late ST (early: 2260 ± 1550 per mm2 vs. late: 2485 ± 1778 per mm2; P = 0.44); neutrophils represented the most prominent subset (early: 1364 ± 923 per mm2 vs. late: 1428 ± 1023 per mm2; P = 0.81). Leukocyte counts were significantly higher compared with a control group of patients with thrombus aspiration in spontaneous myocardial infarction. Neutrophil extracellular traps were observed in 23% of samples. Eosinophils were present in all stent types, with higher numbers in patients with late ST in sirolimus-and everolimus-eluting stents. Conclusion In a large-scale study of histological thrombus analysis from patients presenting with ST, thrombus specimens displayed heterogeneous morphology. Recruitment of leukocytes, particularly neutrophils, appears to be a hallmark of ST. The presence of NETs supports their pathophysiological relevance. Eosinophil recruitment suggests an allergic component to the process of ST

    Fat1 deletion promotes hybrid EMT state, tumour stemness and metastasis

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    FAT1, which encodes a protocadherin, is one of the most frequently mutated genes in human cancers1–5. However, the role and the molecular mechanisms by which FAT1 mutations control tumour initiation and progression are poorly understood. Here, using mouse models of skin squamous cell carcinoma and lung tumours, we found that deletion of Fat1 accelerates tumour initiation and malignant progression and promotes a hybrid epithelial-to-mesenchymal transition (EMT) phenotype. We also found this hybrid EMT state in FAT1-mutated human squamous cell carcinomas. Skin squamous cell carcinomas in which Fat1 was deleted presented increased tumour stemness and spontaneous metastasis. We performed transcriptional and chromatin profiling combined with proteomic analyses and mechanistic studies, which revealed that loss of function of FAT1 activates a CAMK2–CD44–SRC axis that promotes YAP1 nuclear translocation and ZEB1 expression that stimulates the mesenchymal state. This loss of function also inactivates EZH2, promoting SOX2 expression, which sustains the epithelial state. Our comprehensive analysis identified drug resistance and vulnerabilities in FAT1-deficient tumours, which have important implications for cancer therapy. Our studies reveal that, in mouse and human squamous cell carcinoma, loss of function of FAT1 promotes tumour initiation, progression, invasiveness, stemness and metastasis through the induction of a hybrid EMT state

    roma westward migration in europe rethinking political social and methodological challenges

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    The idea for this book stemmed from two symposia that brought together scholars from a range of different countries and disciplines to reflect upon the political and legal context of the mobility of Romani citizens in Europe. Our interest in this topic started with the adoption of a EU Framework for National Roma Integration Strategies in 2011, when Member States were requested to develop integration strategies that were explicitly yet not exclusively targeted at their Roma populations (European Commission 2011). Even though this policy scheme represented an effort to overcome the inadequacies of the anti-discrimination directives to address the social and institutional discrimination suffered by Roma people in Europe, tangible results of such measures have so far been lacking. The symposia, titled "Roma Westward Migration in Europe: Rethinking Political, Social, and Methodological Challenges", addressed the emergence of Roma-specific policies alongside an increasing concern about migration and diversity management. The drive to bring together different disciplinary and methodological approaches to "Roma migration" in Europe, and to explore how such phenomenon has been narrated, policed, politicized or ignored was – and is – rooted in four main considerations. Firstly, we are convinced that putting the focus squarely on the so-called "Roma westward migration" and problematizing the assumptions that underpin such a label contributes to uncover the structural inconsistencies of the European "Roma integration" framework and to question its overall political approach. Secondly, the intersections and overlaps between the categories of "Roma" and of "migrants" show how the classifications of deservingness and of access to welfare resources have shifted in recent years, making explicit the under-studied link between inclusive and securitarian policies. Thirdly, we believe that "Roma migration" provides a unique testing ground to understand how those portrayed as "the others" in contemporary Europe cope and develop counter-strategies in a system in which their options are limited. Fourthly and finally, we strongly support ethnographic accounts as a useful means to evaluate public policies at the local level, as they offer rich data that cannot be captured by national statistics or by surveys alone

    Efficacy and safety of alirocumab in reducing lipids and cardiovascular events.

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