Modelling the end of the Acheulean at global and continental levels suggests widespread persistence into the Middle Palaeolithic

AbstractThe Acheulean is the longest cultural tradition ever practised by humans, lasting for over 1.5 million years. Yet, its end has never been accurately dated; only broad 300–150 thousand years ago (Kya) estimates exist. Here we use optimal linear estimation modelling to infer the extinction dates of the Acheulean at global and continental levels. In Africa and the Near East the Acheulean is demonstrated to end between 174 and 166 Kya. In Europe it is inferred to end between 141 and 130 Kya. The Acheulean’s extinction in Asia occurs later (57–53 Kya), while global models vary depending on how archaeological sites are selected (107–29 Kya). These models demonstrate the Acheulean to have remained a distinct cultural tradition long after the inception of Middle Palaeolithic technologies in multiple continental regions. The complexity of this scenario mirrors the increasingly dynamic nature of the Middle Pleistocene hominin fossil record, suggesting contemporaneous hominin populations to have practised distinct stone-tool traditions.</jats:p

Acidosis Is a Key Regulator of Osteoblast Ecto-Nucleotidase Pyrophosphatase/Phosphodiesterase 1 (NPP1) Expression and Activity

Previous work has shown that acidosis prevents bone nodule formation by osteoblasts in vitro by inhibiting mineralisation of the collagenous matrix. The ratio of phosphate (Pi) to pyrophosphate (PPi) in the bone microenvironment is a fundamental regulator of bone mineralisation. Both Pi and PPi, a potent inhibitor of mineralisation, are generated from extracellular nucleotides by the actions of ecto‐nucleotidases. This study investigated the expression and activity of ecto‐nucleotidases by osteoblasts under normal and acid conditions. We found that osteoblasts express mRNA for a number of ecto‐nucleotidases including NTPdase 1–6 (ecto‐nucleoside triphosphate diphosphohydrolase) and NPP1‐3 (ecto‐nucleotide pyrophosphatase/phosphodiesterase). The rank order of mRNA expression in differentiating rat osteoblasts (day 7) was Enpp1 > NTPdase 4 > NTPdase 6 > NTPdase 5 > alkaline phosphatase > ecto‐5‐nucleotidase > Enpp3 > NTPdase 1 > NTPdase 3 > Enpp2 > NTPdase 2. Acidosis (pH 6.9) upregulated NPP1 mRNA (2.8‐fold) and protein expression at all stages of osteoblast differentiation compared to physiological pH (pH 7.4); expression of other ecto‐nucleotidases was unaffected. Furthermore, total NPP activity was increased up to 53% in osteoblasts cultured in acid conditions (P < 0.001). Release of ATP, one of the key substrates for NPP1, from osteoblasts, was unaffected by acidosis. Further studies showed that mineralised bone formation by osteoblasts cultured from NPP1 knockout mice was increased compared with wildtypes (2.5‐fold, P < 0.001) and was partially resistant to the inhibitory effect of acidosis. These results indicate that increased NPP1 expression and activity might contribute to the decreased mineralisation observed when osteoblasts are exposed to acid conditions

Models of Party Democracy : Patterns of Party Regulation in Post-War European Constitutions

This article investigates the ways in which political parties are codified in modern democratic constitutions, providing a unique cross-sectional and longitudinal overview of the patterns of party constitutionalization in post-war Europe. Although the constitutions of western liberal democracies traditionally have paid little attention to the role of parties, evidence suggests that in contemporary democracies, both old and new, they are increasingly accorded a formal constitutional status. Little is known, however, about the substantive content of their constitutional position or about the normative connotations of their constitutional codification. In this article, we demonstrate that there is a clear correlation between the nature and the intensity of party constitutionalization and the newness and historical experience of democracy and that, with time, the constitutional regulation of the extra-parliamentary organization and the parties’ rights and duties has gained in importance at the expense of their parliamentary and electoral roles. The analysis furthermore suggests that three distinct models of party constitutionalization can be identified – Defending Democracy, Parties in Public Office, and Parties as Public Utilities – each of which is related to a particular conception of party democracy

Coagulation abnormalities of sickle cell disease: Relationship with clinical outcomes and the effect of disease modifying therapies

Sickle cell disease (SCD) is a hypercoagulable state. Patients exhibit increased platelet activation, high plasma levels of markers of thrombin generation, depletion of natural anticoagulant proteins, abnormal activation of the fibrinolytic system, and increased tissue factor expression, even in the non-crisis “steady state.” Furthermore, SCD is characterized by an increased risk of thrombotic complications. The pathogenesis of coagulation activation in SCD appears to be multi-factorial, with contributions from ischemia-reperfusion injury and inflammation, hemolysis and nitric oxide deficiency, and increased sickle RBC phosphatidylserine expression. Recent studies in animal models suggest that activation of coagulation may contribute to the pathogenesis of SCD, but the data on the contribution of coagulation and platelet activation to SCD-related complications in humans are limited. Clinical trials of new generations of anticoagulants and antiplatelet agents, using a variety of clinical endpoints are warranted

Cancer incidence in British vegetarians

Background: Few prospective studies have examined cancer incidence among vegetarians. Methods: We studied 61 566 British men and women, comprising 32 403 meat eaters, 8562 non-meat eaters who did eat fish ('fish eaters') and 20 601 vegetarians. After an average follow-up of 12.2 years, there were 3350 incident cancers of which 2204 were among meat eaters, 317 among fish eaters and 829 among vegetarians. Relative risks (RRs) were estimated by Cox regression, stratified by sex and recruitment protocol and adjusted for age, smoking, alcohol, body mass index, physical activity level and, for women only, parity and oral contraceptive use. Results: There was significant heterogeneity in cancer risk between groups for the following four cancer sites: stomach cancer, RRs (compared with meat eaters) of 0.29 (95% CI: 0.07–1.20) in fish eaters and 0.36 (0.16–0.78) in vegetarians, P for heterogeneity=0.007; ovarian cancer, RRs of 0.37 (0.18–0.77) in fish eaters and 0.69 (0.45–1.07) in vegetarians, P for heterogeneity=0.007; bladder cancer, RRs of 0.81 (0.36–1.81) in fish eaters and 0.47 (0.25–0.89) in vegetarians, P for heterogeneity=0.05; and cancers of the lymphatic and haematopoietic tissues, RRs of 0.85 (0.56–1.29) in fish eaters and 0.55 (0.39–0.78) in vegetarians, P for heterogeneity=0.002. The RRs for all malignant neoplasms were 0.82 (0.73–0.93) in fish eaters and 0.88 (0.81–0.96) in vegetarians (P for heterogeneity=0.001). Conclusion: The incidence of some cancers may be lower in fish eaters and vegetarians than in meat eaters

The architecture of innovation: Tracking face-to-face interactions with UbiComp technologies

The layouts of the buildings we live in shape our everyday lives. In office environments, building spaces affect employees' communication, which is crucial for productivity and innovation. However, accurate measurement of how spatial layouts affect interactions is a major challenge and traditional techniques may not give an objective view.We measure the impact of building spaces on social interactions using wearable sensing devices. We study a single organization that moved between two different buildings, affording a unique opportunity to examine how space alone can affect interactions. The analysis is based on two large scale deployments of wireless sensing technologies: short-range, lightweight RFID tags capable of detecting face-to-face interactions. We analyze the traces to study the impact of the building change on social behavior, which represents a first example of using ubiquitous sensing technology to study how the physical design of two workplaces combines with organizational structure to shape contact patterns.This is the author accepted manuscript. The final version is available at http://dl.acm.org/citation.cfm?id=2632056&CFID=528294814&CFTOKEN=36484024

Early stage blunting causes rapid reductions in stone tool performance

Palaeolithic stone technologies have never been investigated in terms of how sharpness influences their ability to cut. In turn, there is little understanding of how quickly stone cutting edges blunt, how past populations responded to any consequent changes in performance, or how these factors influenced the Palaeolithic archaeological record. Presented here is experimental data quantitatively detailing how variation in edge sharpness influences stone tool cutting performance. Significant increases in force (N) and material displacement (mm) requirements occur rapidly within early stages of blunting, with a single abrasive cutting stroke causing, on average, a 38% increase in the force needed to initiate a cut. In energetic terms, this equates to a 70% increase in work (J). Subsequent to early stages of blunting we identify a substantial drop in the impact of additional edge abrasion. We also demonstrate how edge (included) angle significantly influences cutting force and energy requirements and how it co-varies with sharpness. Amongst other conclusions, we suggest that rapid reductions in performance due to blunting may account for the abundance of lithic artefacts at some archaeological sites, the speed that resharpening behaviours altered tool forms, and the lack of microscopic wear traces on many lithic implements