The Father, the Son and the Holy Ghost:A Grounded Theory approach to the comparative study of decision-making in the NAC and PSC

Studies of the relationship between the EU and NATO often focus on the limitations of cooperation, be it at the political or the operational level. However, little is known about the functioning of the political institutional linkages between the EU and NATO. This article therefore studies the main decision-making bodies of the two organisations at the political, ambassadorial level, namely the Political and Security Committee (PSC) of the EU and the North Atlantic Council (NAC) in NATO, as well as their joint meetings. The article employs an inductive Grounded Theory approach, drawing on open-ended interviews with PSC and NAC ambassadors, which reveal direct insights from the objects of analysis. The findings emphasise the impact of both structural and more agency-related categories on decision-making in these three fora. The article thus addresses both the paucity of study on these bodies more broadly and the complete lacuna on joint PSC–NAC meetings specifically, warranting the inductive approach this article endorses

Observation of B+ -> K+ eta gamma

We report measurements of radiative B decays with K eta gamma final states, using a data sample of 253 /fb recorded at the Upsilon(4S) resonance with the Belle detector at the KEKB e+e- storage ring. We observe B+ -> K+ eta gamma for the first time with a branching fraction of (8.4 +- 1.5(stat) +1.2 -0.9(syst)) X 10^{-6} for M(Keta) K0 eta gamma. We also search for B -> K3*(1780) gamma.Comment: 12 pages, 5 figures, accepted by Phys. Lett.

Principles of ecDNA random inheritance drive rapid genome change and therapy resistance in human cancers

The foundational principles of Darwinian evolution are variation, selection, and identity by descent. Oncogene amplification on extrachromosomal DNA (ecDNA) is a common event, driving aggressive tumour growth, drug resistance, and shorter survival in patients. Currently, the impact of non-chromosomal oncogene inheritance - random identity by descent - is not well understood. Neither is the impact of ecDNA on variation and selection. Here, integrating mathematical modeling, unbiased image analysis, CRISPR-based ecDNA tagging, and live-cell imaging, we identify a set of basic "rules" for how random ecDNA inheritance drives oncogene copy number and distribution, resulting in extensive intratumoural ecDNA copy number heterogeneity and rapid adaptation to metabolic stress and targeted cancer treatment. Observed ecDNAs obligatorily benefit host cell survival or growth and can change within a single cell cycle. In studies ranging from well-curated, patient-derived cancer cell cultures to clinical tumour samples from patients with glioblastoma and neuroblastoma treated with oncogene-targeted drugs, we show how these ecDNA inheritance "rules" can predict, a priori, some of the aggressive features of ecDNA-containing cancers. These properties are entailed by their ability to rapidly change their genomes in a way that is not possible for cancers driven by chromosomal oncogene amplification. These results shed new light on how the non-chromosomal random inheritance pattern of ecDNA underlies poor outcomes for cancer patients

ecDNA hubs drive cooperative intermolecular oncogene expression

Extrachromosomal DNA (ecDNA) is prevalent in human cancers and mediates high expression of oncogenes through gene amplification and altered gene regulation. Gene induction typically involves cis-regulatory elements that contact and activate genes on the same chromosome. Here we show that ecDNA hubs-clusters of around 10-100 ecDNAs within the nucleus-enable intermolecular enhancer-gene interactions to promote oncogene overexpression. ecDNAs that encode multiple distinct oncogenes form hubs in diverse cancer cell types and primary tumours. Each ecDNA is more likely to transcribe the oncogene when spatially clustered with additional ecDNAs. ecDNA hubs are tethered by the bromodomain and extraterminal domain (BET) protein BRD4 in a MYC-amplified colorectal cancer cell line. The BET inhibitor JQ1 disperses ecDNA hubs and preferentially inhibits ecDNA-derived-oncogene transcription. The BRD4-bound PVT1 promoter is ectopically fused to MYC and duplicated in ecDNA, receiving promiscuous enhancer input to drive potent expression of MYC. Furthermore, the PVT1 promoter on an exogenous episome suffices to mediate gene activation in trans by ecDNA hubs in a JQ1-sensitive manner. Systematic silencing of ecDNA enhancers by CRISPR interference reveals intermolecular enhancer-gene activation among multiple oncogene loci that are amplified on distinct ecDNAs. Thus, protein-tethered ecDNA hubs enable intermolecular transcriptional regulation and may serve as units of oncogene function and cooperative evolution and as potential targets for cancer therapy

SEARCH FOR THE t AND b-prime QUARKS IN HADRONIC DECAYS OF THE Z0 BOSON

We present a search for the third generation up type quark t and a possible fourth down type quark b' in hadronic Z0 decays observed in DELPHI at the LEP collider. For any scenario with a decay through the charged current or into a charged Higgs with a mass at least 6 GeV/c2 below the t and 3 GeVc2 below the b' mass, we set a lower limit for the t quark mass at 44.0 GeV/c2 and for the b' mass at 44.5 GeV/c2. For specific scenarios the mass limits are slightly higher, e.g. for charged current decays the limits are 44.5 and 45.0 GeV/c2 respectively, where all limits are given at a 95% confidence level. © 1990.0SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016

Background Traumatic brain injury (TBI) and spinal cord injury (SCI) are increasingly recognised as global health priorities in view of the preventability of most injuries and the complex and expensive medical care they necessitate. We aimed to measure the incidence, prevalence, and years of life lived with disability (YLDs) for TBI and SCI from all causes of injury in every country, to describe how these measures have changed between 1990 and 2016, and to estimate the proportion of TBI and SCI cases caused by different types of injury. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016 to measure the global, regional, and national burden of TBI and SCI by age and sex. We measured the incidence and prevalence of all causes of injury requiring medical care in inpatient and outpatient records, literature studies, and survey data. By use of clinical record data, we estimated the proportion of each cause of injury that required medical care that would result in TBI or SCI being considered as the nature of injury. We used literature studies to establish standardised mortality ratios and applied differential equations to convert incidence to prevalence of long-term disability. Finally, we applied GBD disability weights to calculate YLDs. We used a Bayesian meta-regression tool for epidemiological modelling, used causespecific mortality rates for non-fatal estimation, and adjusted our results for disability experienced with comorbid conditions. We also analysed results on the basis of the Socio-demographic Index, a compound measure of income per capita, education, and fertility. Findings In 2016, there were 27.08 million (95% uncertainty interval [UI] 24.30-30.30 million) new cases of TBI and 0.93 million (0.78-1.16 million) new cases of SCI, with age-standardised incidence rates of 369 (331-412) per 100 000 population for TBI and 13 (11-16) per 100 000 for SCI. In 2016, the number of prevalent cases of TBI was 55.50 million (53.40-57.62 million) and of SCI was 27.04 million (24.98-30.15 million). From 1990 to 2016, the agestandardised prevalence of TBI increased by 8.4% (95% UI 7.7 to 9.2), whereas that of SCI did not change significantly (-0.2% [-2.1 to 2.7]). Age-standardised incidence rates increased by 3.6% (1.8 to 5.5) for TBI, but did not change significantly for SCI (-3.6% [-7.4 to 4.0]). TBI caused 8.1 million (95% UI 6.0-10.4 million) YLDs and SCI caused 9.5 million (6.7-12.4 million) YLDs in 2016, corresponding to age-standardised rates of 111 (82-141) per 100 000 for TBI and 130 (90-170) per 100 000 for SCI. Falls and road injuries were the leading causes of new cases of TBI and SCI in most regions. Interpretation TBI and SCI constitute a considerable portion of the global injury burden and are caused primarily by falls and road injuries. The increase in incidence of TBI over time might continue in view of increases in population density, population ageing, and increasing use of motor vehicles, motorcycles, and bicycles. The number of individuals living with SCI is expected to increase in view of population growth, which is concerning because of the specialised care that people with SCI can require. Our study was limited by data sparsity in some regions, and it will be important to invest greater resources in collection of data for TBI and SCI to improve the accuracy of future assessments. © 2018 The Author(s)

Search for scalar quarks in Z0 decays

A search has been made for pairs of scalar quarks (squarks) produced in e+e- annihilations at LEP (√s≃MZ0), and decaying into a standard quark and a neutral, non-interacting, stable, massive particle (the lightest supersymmetric particle, LSP). The search has been conducted for differences in the mass of the squark and LSP of 2 GeV/c2 and above. Up squarks with masses below 42 GeV/c2 and down squarks below 43 GeV/c2 were excluded. Six squark flavours degenerate in mass were excluded below 45 GeV/c2.0SCOPUS: ar.jinfo:eu-repo/semantics/publishe