Cosmic-ray energy spectrum and composition up to the ankle - the case for a second Galactic component

We have carried out a detailed study to understand the observed energy spectrum and composition of cosmic rays with energies up to ~10^18 eV. Our study shows that a single Galactic component with subsequent energy cut-offs in the individual spectra of different elements, optimised to explain the observed spectra below ~10^14 eV and the knee in the all-particle spectrum, cannot explain the observed all-particle spectrum above ~2x10^16 eV. We discuss two approaches for a second component of Galactic cosmic rays -- re-acceleration at a Galactic wind termination shock, and supernova explosions of Wolf-Rayet stars, and show that the latter scenario can explain almost all observed features in the all-particle spectrum and the composition up to ~10^18 eV, when combined with a canonical extra-galactic spectrum expected from strong radio galaxies or a source population with similar cosmological evolution. In this two-component Galactic model, the knee at ~ 3x10^15 eV and the second knee at ~10^17 eV in the all-particle spectrum are due to the cut-offs in the first and second components, respectively. We also discuss several variations of the extra-galactic component, from a minimal contribution to scenarios with a significant component below the ankle (at ~4x10^18 eV), and find that extra-galactic contributions in excess of regular source evolution are neither indicated nor in conflict with the existing data. Our main result is that the second Galactic component predicts a composition of Galactic cosmic rays at and above the second knee that largely consists of helium or a mixture of helium and CNO nuclei, with a weak or essentially vanishing iron fraction, in contrast to most common assumptions. This prediction is in agreement with new measurements from LOFAR and the Pierre Auger Observatory which indicate a strong light component and a rather low iron fraction between ~10^17 and 10^18 eV.Comment: Added Table 4; Published in A&A, 595 (2016) A33 (Highlight paper

Cenozoic inversion of the Weald-Boulonnais and the Dover Strait: new data

The Boulonnais is a former marine gulf superimposed on a zone of tectonic inversion, which was already excavated at least at the early Middle Eocene. New sedimentalogical and paleopedological data discover within the Boulonnais and fresh seismic sections able now to better understand the process of inversion step by step. The initial breaching probably took place in the late Eocene. The Dover Strait was probably open during the Lutetian, a part of the Oligocene and of the Late Neogene. Oligocene and Pliocene faunal assemblages are identical on both sides of the Strait. It was closed again for tectonic and eustatic reasons in the early Quaternary and reopen lately from Last Interglacial. This reopening is related with the evolution of the Western Channel and of its paleovalley system. This inversion of the Variscan front accommodates most of the shortening induced by the Pyrenean Orogen on the Western border of the European plate. The inversion of the Dover Strait region is almost synchronic with those of other basins of the Channel and North Sea areas. Tectonic, geomorphologic and climatic implications of this dynamic are discussed within the Western European context

The perspective of people with axial spondyloarthritis regarding physiotherapy : room for the implementation of a more active approach

Objectives. Physiotherapy is recommended in the management of people with axial spondyloarthritis (axSpA), with new insights into its preferred content and dosage evolving. The aim of this study was to describe the use and preferences regarding individual and group physiotherapy among people with axSpA. Methods. A cross-sectional survey was conducted among people with axSpA living in The Netherlands (NL) and Switzerland (CH). Results. Seven hundred and thirteen people with axSpA participated (56.7% male, median age 55 years, median Assessment of Spondyloarthritis International Society Health Index score 4.2). Response rates were 45% (n¼206) in NL and 29% in CH (n¼507). Of these participants, 83.3% were using or had been using physiotherapy. Individual therapy only was used or had been used by 36.7%, a combination of individual plus land- and water-based group therapy by 29.1% and group therapy by only 5.3%. Fewer than half of the participants attending individual therapy reported active therapy (such as aerobic, muscle strength and flexibility exercises). Although the majority (75.9%) were not aware of the increased cardiovascular risk, participants showed an interest in cardiovascular training, either individually or in a supervised setting. If supervised, a majority, in CH (75.0%) more than in NL (55.7%), preferred supervision by a specialized physiotherapist. Conclusion. The majority of people with axSpA use or have used physiotherapy, more often in an individual setting than in a group setting. The content of individual therapy should be more active; in both therapy settings, aerobic exercises should be promoted. In particular, enabling people with axSpA to perform exercises independently would meet their needs and might enhance their daily physical activity

A quadrature filter approach for registration accuracy assessment of fundus images

This paper presents a method to automatically assess the accuracy of image registration. It is applicable to images in which vessels are the main landmarks such as fundus images and angiography. The method simultaneously exploits not only the position, but also the intensity profile across the vasculatures. The accuracy measure is defined as the energy of the odd component of the 1D vessel profile in the difference image divided by the total energy of the corresponding vessels in the constituting images. Scale and orientation-selective quadrature filter banks have been employed to analyze the 1D signal profiles. Subsequently, the relative energy measure has been calibrated such that the measure translates to a spatial misalignment in pixels. The method was validated on a fundus image dataset from a diabetic retinopathy screening program at the Rotterdam Eye Hospital. An evaluation showed that the proposed measure assesses the registration accuracy with a bias of -0.1 pixels and a precision (standard deviation) of 0.9 pixels. The small Fourier footprint of the orientation selective quadrature filters makes the method robust against noise

Thyroid status and mortality in nonagenarians from long-lived families and the general population

Pathophysiology, epidemiology and therapy of agein

Oxidative stress and inflammation in a spectrum of epileptogenic cortical malformations: molecular insights into their interdependence

Oxidative stress (OS) occurs in brains of patients with epilepsy and coincides with brain inflammation, and both phenomena contribute to seizure generation in animal models. We investigated whether expression of OS and brain inflammation markers co-occurred also in resected brain tissue of patients with epileptogenic cortical malformations: hemimegalencephaly (HME), focal cortical dysplasia (FCD) and cortical tubers in tuberous sclerosis complex (TSC). Moreover, we studied molecular mechanisms linking OS and inflammation in an in vitro model of neuronal function. Untangling interdependency and underlying molecular mechanisms might pose new therapeutic strategies for treating patients with drug-resistant epilepsy of different etiologies. Immunohistochemistry was performed for specific OS markers xCT and iNOS and brain inflammation markers TLR4, COX-2 and NF-κB in cortical tissue derived from patients with HME, FCD IIa, IIb and TSC. Additionally, we studied gene expression of these markers using the human neuronal cell line SH-SY5Y in which OS was induced using H 2 O 2 . OS markers were higher in dysmorphic neurons and balloon/giant cells in cortex of patients with FCD IIb or TSC. Expression of OS markers was positively correlated to expression of brain inflammation markers. In vitro, 100 µM, but not 50 µM, of H 2 O 2 increased expression of TLR4, IL-1β and COX-2. We found that NF-κB signaling was activated only upon stimulation with 100 µM H 2 O 2 leading to upregulation of TLR4 signaling and IL-1β. The NF-κB inhibitor TPCA-1 completely reversed this effect. Our results show that OS positively correlates with neuroinflammation and is particularly evident in brain tissue of patients with FCD IIb and TSC. In vitro, NF-κB is involved in the switch to an inflammatory state after OS. We propose that the extent of OS can predict the neuroinflammatory state of the brain. Additionally, antioxidant treatments may prevent the switch to inflammation in neurons thus targeting multiple epileptogenic processes at once

Prevalence of BRCA1 in a hospital-based population of Dutch breast cancer patients

The prevalence of disease-related BRCA1 mutations was investigated in 642 Dutch breast cancer patients not selected for family history or age at diagnosis. They were tested for germline mutations in the BRCA1 gene using an assay which detects small deletions and insertions (DSDI), as well as the two major genomic founder deletions present in the Dutch population. Data on family history and bilateral breast cancer were obtained retrospectively. Ten protein truncating mutations were detected and one in-frame deletion with an unknown relation to disease risk. Four patients carried the Dutch founder deletion of exon 22. Based on these results the estimated prevalence of breast cancer in the general population in the Netherlands attributable to BRCA1 mutations is 2.1%. Under 40 years-of-age and under 50 years-of-age this prevalence is 9.5% and 6.4%, respectively. All mutation carriers were under 50 years-of-age at diagnosis of the first breast cancer, and five did not have any relative with breast cancer. The proportions of bilateral breast cancer in the mutation carriers and non-carriers did not differ from each other. These data indicate that in the general Dutch breast cancer population the great majority of BRCA1 mutations will be found in women diagnosed under 50 years-of-age. © 2000 Cancer Research Campaig