Pedigree-based Bayesian modelling of radiocarbon dates

Within the last decade, archaeogenetic analysis has revolutionized archaeological research and enabled novel insights into mobility, relatedness and health of past societies. Now, it is possible to develop these results further and integrate archaeogenetic insights into biological relatedness with radiocarbon dates as means of chronologically sequenced information. In our article, we demonstrate the potential of combining relative chronological information with absolute radiocarbon dates by Bayesian interpretation in order to improve age determinations. Using artificial pedigrees with four sets of simulated radiocarbon dates we show that the combination of relationship information with radiocarbon dates improves the age determination in many cases at least between 20 to 50%. Calibrated age ranges are more constrained than simply calibrating radiocarbon ages independently from each other. Thereby, the precision of modelled ages depends on the precision of the single radiocarbon dates, the number of modelled generations, the shape of the calibration curve and the availability of samples that can be precisely fixed in time due to specific patterns in the calibration curve (“anchor points”). Ambiguous calibrated radiocarbon dates, which are caused by inversions of the calibration curve, can be partly or almost entirely resolved through Bayesian modelling based upon information from pedigrees. Finally, we discuss selected case studies of biological pedigrees achieved for Early Bronze Age Southern Germany by recent archaeogenetic analysis, whereby the sites and pedigrees differ with regard to the quality of information, which can be used for a Bayesian model of the radiocarbon dates. In accordance with the abstract models, radiocarbon dates can again be better constrained and are therefore more applicable for archaeological interpretation and chronological placement of the dated individuals

Neoliberal growth models, monetary union and the Euro Crisis : a post-Keynesian perspective

The paper offers an account of the Euro crisis based on post-Keynesian monetary theory and its typology of demand regimes. Neoliberalism has transformed social and financial relations in Europe but it has not given rise to a sustained profit-led growth process. Instead, growth has relied either on financial bubbles and rising household debt (‘debt-driven growth’) or on net exports (‘export-driven growth’). In Europe the financial crisis has been amplified by an economic policy architecture (the Stability and Growth Pact) that aimed at restricting the role of fiscal policy and monetary policy. This neoliberal economic policy regime in conjunction with the separation of monetary and fiscal spheres has turned the financial crisis of 2007 into a sovereign debt crisis in southern Europe

The effects of financialisation and financial development on investment: Evidence from firm-level data in Europe

In this paper we estimate the effects of financialization on physical investment in selected western European countries using panel data based on the balance-sheets of publicly listed non-financial companies (NFCs) supplied by Worldscope for the period 1995-2015. We find robust evidence of an adverse effect of both financial payments (interests and dividends) and financial incomes on investment in fixed assets by the NFCs. This finding is robust for both the pool of all Western European firms and single country estimations. The negative impacts of financial incomes are non-linear with respect to the companies’ size: financial incomes crowd-out investment in large companies, and have a positive effect on the investment of only small, relatively more credit-constrained companies. Moreover, we find that a higher degree of financial development is associated with a stronger negative effect of financial incomes on companies’ investment. This finding challenges the common wisdom on ‘finance-growth nexus’. Our findings support the ‘financialization thesis’ that the increasing orientation of the non-financial sector towards financial activities is ultimately leading to lower physical investment, hence to stagnant or fragile growth, as well as long term stagnation in productivity

Targeted therapy for high-grade glioma with the TGF-β2 inhibitor trabedersen: results of a randomized and controlled phase IIb study

This randomized, open-label, active-controlled, dose-finding phase IIb study evaluated the efficacy and safety of trabedersen (AP 12009) administered intratumorally by convection-enhanced delivery compared with standard chemotherapy in patients with recurrent/refractory high-grade glioma. One hundred and forty-five patients with central reference histopathology of recurrent/refractory glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA) were randomly assigned to receive trabedersen at doses of 10 or 80 µM or standard chemotherapy (temozolomide or procarbazine/lomustine/vincristine). Primary endpoint was 6-month tumor control rate, and secondary endpoints included response at further timepoints, survival, and safety. Six-month tumor control rates were not significantly different in the entire study population (AA and GBM). Prespecified AA subgroup analysis showed a significant benefit regarding the 14-month tumor control rate for 10 µM trabedersen vs chemotherapy (p= .0032). The 2-year survival rate had a trend for superiority for 10 µM trabedersen vs chemotherapy (p = .10). Median survival for 10 µM trabedersen was 39.1 months compared with 35.2 months for 80 µM trabedersen and 21.7 months for chemotherapy (not significant). In GBM patients, response and survival results were comparable among the 3 arms. Exploratory analysis on GBM patients aged ≤55 years with Karnofsky performance status >80% at baseline indicated a 3-fold survival at 2 and 3 years for 10 µM trabedersen vs chemotherapy. The frequency of patients with related or possibly drug-related adverse events was higher with standard chemotherapy (64%) than with 80 µM trabedersen (43%) and 10 µM trabedersen (27%). Superior efficacy and safety for 10 µM trabedersen over 80 µM trabedersen and chemotherapy and positive risk–benefit assessment suggest it as the optimal dose for further clinical development in high-grade glioma

The state and class discipline: European labour market policy after the financial crisis

This paper looks at two related labour market policies that have persisted and even proliferated across Europe both before and after the financial crisis: wage restraint, and punitive workfare programmes. It asks why these policies, despite their weak empirical records, have been so durable. Moving beyond comparative-institutionalist explanations which emphasise institutional stickiness, it draws on Marxist and Kaleckian ideas around the concept of ‘class discipline’. It argues that under financialisation, the need for states to implement policies that discipline the working class is intensified, even if these policies do little to enable (and may even counteract) future stability. Wage restraint and punitive active labour market policies are two examples of such measures. Moreover, this disciplinary impetus has subverted and marginalised regulatory labour market institutions, rather than being embedded within them

Ancient DNA reveals admixture history and endogamy in the prehistoric Aegean (advance online)

The Neolithic and Bronze Ages were highly transformative periods forthe genetic history of Europe but for the Aegean—a region fundamentalto Europe’s prehistory—the biological dimensions of cultural transitionshave been elucidated only to a limited extent so far. We have analysed newlygenerated genome-wide data from 102 ancient individuals from Crete, theGreek mainland and the Aegean Islands, spanning from the Neolithic tothe Iron Age. We found that the early farmers from Crete shared the sameancestry as other contemporaneous Neolithic Aegeans. In contrast, the endof the Neolithic period and the following Early Bronze Age were marked by‘eastern’ gene flow, which was predominantly of Anatolian origin in Crete.Confirming previous findings for additional Central/Eastern Europeanancestry in the Greek mainland by the Middle Bronze Age, we additionallyshow that such genetic signatures appeared in Crete gradually from theseventeenth to twelfth centuries bc, a period when the influence of themainland over the island intensified. Biological and cultural connectednesswithin the Aegean is also supported by the finding of consanguineousendogamy practiced at high frequencies, unprecedented in the globalancient DNA record. Our results highlight the potential of archaeogenomicapproaches in the Aegean for unravelling the interplay of genetic admixture,marital and other cultural practice

A critique of neo-mercantilist analyses of Icelandic political economy and crisis

Iceland’s journey from rags to riches in the 20th century is related, in the dominant discourse, to its gaining independence in 1944. This discourse played a significant role in both the legitimation of the finance-dominated growth model in the 1990s and 2000s and in the latter’s defence as it came under scrutiny before its collapse in October 2008. It is therefore ironic – or perhaps, in some sense, logical – to find dominant analyses of the crisis arising from the neo-mercantilist tradition. Drawing on Marxist critiques of neo-mercantilism, we challenge these interventions and thus seek to redress the neglect of social struggle in the dominant discourse

Stone Age Yersinia pestis genomes shed light on the early evolution, diversity, and ecology of plague

The bacterial pathogenYersinia pestisgave rise to devastating outbreaks throughouthuman history, and ancient DNA evidence has shown it afflicted human populations asfar back as the Neolithic.Y. pestisgenomes recovered from the Eurasian Late Neolithic/Early Bronze Age (LNBA) period have uncovered key evolutionary steps that led to itsemergence from aYersinia pseudotuberculosis-like progenitor; however, the number ofreconstructed LNBA genomes are too few to explore its diversity during this criticalperiod of development. Here, we present 17Y. pestisgenomes dating to 5,000 to 2,500y BP from a wide geographic expanse across Eurasia. This increased dataset enabled usto explore correlations between temporal, geographical, and genetic distance. Ourresults suggest a nonflea-adapted and potentially extinct single lineage that persistedover millennia without significant parallel diversification, accompanied by rapid dis-persal across continents throughout this period, a trend not observed in other pathogensfor which ancient genomes are available. A stepwise pattern of gene loss provides fur-ther clues on its early evolution and potential adaptation. We also discover the presenceof theflea-adapted form ofY. pestisin Bronze Age Iberia, previously only identified inin the Caucasus and the Volga regions, suggesting a much wider geographic spread ofthis form ofY. pestis. Together, these data reveal the dynamic nature of plague’s forma-tive years in terms of its early evolution and ecology

Using Y-chromosome capture enrichment to resolve haplogroup H2 shows new evidence for a two-Path Neolithic expansion to Western Europe

Uniparentally-inherited markers on mitochondrial DNA (mtDNA) and the non-recombining regions of the Y chromosome (NRY), have been used for the past 30 years to investigate the history of humans from a maternal and paternal perspective.Researchers have preferred mtDNA due to its abundance in the cells, and comparatively high substitution rate. Conversely, the NRY is less susceptible to back mutations and saturation, and is potentially more informative than mtDNA owing to its longer sequence length. However, due to comparatively poor NRY coverage via shotgun sequencing, and the relatively low and biased representation of Y-chromosome variants on capture arrays such as the 1240K, ancient DNA studies often fail to utilize the unique perspective that the NRY can yield.Here we introduce a new DNA enrichment assay, coined YMCA (Y-mappable capture assay), that targets the “mappable” regions of the NRY. We show that compared to low-coverage shotgun sequencing and 1240K capture, YMCA significantly improves the coverage and number of sites hit on the NRY, increasing the number of Y-haplogroup informative SNPs, and allowing for the identification of previously undiscovered variants.To illustrate the power of YMCA, we show that the analysis of ancient Y-chromosome lineages can help to resolve Y-chromosomal haplogroups. As a case study, we focus on H2, a haplogroup associated with a critical event in European human history: the Neolithic transition. By disentangling the evolutionary history of this haplogroup, we further elucidate the two separate paths by which early farmers expanded from Anatolia and the Near East to western Europe.Competing Interest StatementThe authors have declared no competing interest.Introduction Results and Discussion - Validating the performance of YMCA - Application of YMCA to YHG H2 as a case study - Identifying diagnostic SNPs for improved YHG H2 resolution Discussion Materials and Methods - Data - Contamination quality filtering - Method of Y Haplogroup Assignment - Comparing the Performance of our Y-capture Array Phylogenetic Tree Reconstructio