A case of multiple sclerosis—like relapsing remitting encephalomyelitis following allogeneic hematopoietic stem cell transplantation and a review of the published literature

Complications involving the central nervous system (CNS) occur in 9–14% of patients following allogeneic hematopoietic stem cell transplantation (HSCT), including stroke-like episodes, demyelination, encephalitis, and nonspecific neurological symptoms. Here we report a case of multiple sclerosis (MS) like relapsing remitting encephalomyelitis following allogeneic HSCT, which did not respond to disease modifying therapies (DMTs) and “domino” autologous HSCT. A 53-year-old male was treated with allogeneic HSCT for lymphoid blast transformation of chronic myeloid leukemia. Ten months later he presented with confusion, slurred speech, left sided facial weakness and ataxia. A magnetic resonance imaging brain scan showed multiple enhancing tumefactive lesions. Neuromyelitis optica (NMO) and myelin oligodendrocyte glycoprotein (MOG) antibodies were negative. After extensive investigations for infections, autoimmune disorders and recurrence of malignancy, he underwent brain biopsy, which showed a macrophage rich lesion with severe myelin loss but axonal preservation indicating a demyelinating pathology. Although his symptoms improved with corticosteroids, he relapsed five months later. In the absence of any systemic features suggesting graft versus host disease (GvHD), his presentation was thought to be compatible with MS. The illness followed an aggressive course that did not respond to glatiramer acetate and natalizumab. He was therefore treated with “domino” autologous HSCT, which also failed to induce long-term remission. Despite further treatment with ocrelizumab, he died of progressive disease. An autopsy limited to the examination of brain revealed multifocal destructive leukoencephalopathy with severe myelin and axonal loss. Immunohistochemistry showed macrophage located in the perivascular area, with no T or B lymphocytes. The appearance was unusual and not typical for chronic MS plaques. Reported cases of CNS demyelination following allogeneic HSCT are very limited in the literature, especially in relation to histopathological examination. Although the clinical disease course of our patient following allogeneic HSCT resembled an “MS-like” relapsing remitting encephalomyelitis, the autopsy examination did not show any evidence of active inflammation. The impact of DMTs and HSCT on the histological appearance of “MS-like” CNS pathologies is unknown. Therefore, reporting this and similar cases will improve our awareness and understanding of underlying disease mechanisms

The DRIFT Dark Matter Experiments

The current status of the DRIFT (Directional Recoil Identification From Tracks) experiment at Boulby Mine is presented, including the latest limits on the WIMP spin-dependent cross-section from 1.5 kg days of running with a mixture of CS2 and CF4. Planned upgrades to DRIFT IId are detailed, along with ongoing work towards DRIFT III, which aims to be the world's first 10 m3-scale directional Dark Matter detector.Comment: Proceedings of the 3rd International conference on Directional Detection of Dark Matter (CYGNUS 2011), Aussois, France, 8-10 June 201

Provision of long-term monitoring and late effects services following adult allogeneic haematopoietic stem cell transplant: a survey of UK NHS-based programmes

Despite international guidelines, optimal delivery models of late effects (LE) services for HSCT patients are unclear from the clinical, organizational and economic viewpoints. To scope current LE service delivery models within the UK NHS (National Health Service), in 2014, we surveyed the 27 adult allogeneic HSCT centres using a 30-question online tool, achieving a 100% response rate. Most LE services were led and delivered by senior physicians (>80% centres). Follow-up was usually provided in a dedicated allograft or LE clinic for the first year (>90% centres), but thereafter attrition meant that only ~50% of patients were followed after 5 years. Most centres (69%) had a standard operating procedure for long-term monitoring but access to a LE Multi-Disciplinary Team was rare (19% centres). Access to medical specialities necessary for LE management was good, but specialist interest in long-term HSCT complications was uncommon. Some screening (endocrinopathy, cardiovascular) was near universal, but other areas were more limited (mammography, cervical smears). Funding of extra staff and investigations were the most commonly perceived barriers to implementation of LE services. This survey shows variation in the long-term follow-up of allogeneic HSCT survivors within the UK NHS and further work is warranted to optimize effective, sustainable and affordable models of LE service delivery among this group

Charge amplification concepts for direction-sensitive dark matter detectors

Direction measurement of weakly interacting massive particles in time-projection chambers can provide definite evidence of their existence and help to determine their properties. This article demonstrates several concepts for charge amplification in time-projection chambers that can be used in direction-sensitive dark matter search experiments. We demonstrate reconstruction of the 'head-tail' effect for nuclear recoils above 100keV, and discuss the detector performance in the context of dark matter detection and scaling to large detector volumes.Comment: 15 pages, 9 figure

The large-scale shock in the cluster of galaxies Hydra A

We analyzed a deep XMM-Newton observation of the cluster of galaxies Hydra A, focusing on the large-scale shock discovered as a surface brightness discontinuity in Chandra images. The shock front can be seen both in the pressure map and in temperature profiles in several sectors. The Mach numbers determined from the temperature jumps are in good agreement with the Mach numbers derived from EPIC/pn surface brightness profiles and previously from Chandra data and are consistent with M~1.3. The estimated shock age in the different sectors using a spherically symmetric point explosion model ranges between 130 and 230 Myr and the outburst energy between 1.5 and 3e61 ergs. The shape of the shock seen in the pressure map can be approximated with an ellipse centered 70 kpc towards the NE from the cluster center. We aimed to develop a better model that can explain the offset between the shock center and the AGN and give a consistent result on the shock age and energy. To this end, we performed 3D hydrodynamical simulations in which the shock is produced by a symmetrical pair of AGN jets launched in a spherical galaxy cluster. As an explanation of the observed offset of the shock center, we consider large-scale bulk flows in the intracluster medium. The simulation successfully reproduces the size, ellipticity, and average Mach number of the observed shock front. The predicted age of the shock is 160 Myr and the total input energy 3e61 erg. Both values are within the range determined by the spherically symmetric model. Matching the observed 70 kpc offset of the shock ellipse from the cluster center requires large-scale coherent motions with a high velocity of 670 km/s. We discuss the feasibility of this scenario and offer alternative ways to produce the offset and to further improve the simulation.Comment: 14 pages, accepted for publication in A&A, minor revision compared to previous versio

Suzaku broad-band spectroscopy of RX J1347.5-1145: constraints on the extremely hot gas and non-thermal emission

We present the results from the analysis of long Suzaku observations of the most X-ray luminous galaxy cluster RX J1347.5-1145 at z=0.451. Aims: We study physical properties of the hot (~20 keV) gas clump in the south-east (SE) region discovered by the Sunyaev-Zel'dovich (SZ) effect observations, to understand the gas physics of a violent cluster merger. We also explore a signature of non-thermal emission using the hard X-ray data. Results: We find that the single-temperature model fails to reproduce the continuum emission and Fe-K lines measured by XIS simultaneously. The two-temperature model with a very hot component improves the fit, although the XIS data can only give a lower bound on its temperature. We detect the hard X-ray emission in the 12-40 keV band at the 7 sigma level; however, the significance becomes marginal when the systematic error in the background estimation is included. With the Suzaku + Chandra joint analysis, we determine the temperature of the SE excess component to be 25.3^{+6.1}_{-4.5} ^{+6.9}_{-9.5} keV (90% statistical and systematic errors), which is in an excellent agreement with the previous SZ + X-ray analysis. This is the first time that the X-ray spectroscopy alone gives a good measurement of the temperature of the hot component in the SE region, which is made possible by Suzaku's unprecedented sensitivity to the wide X-ray band. These results strongly indicate that the cluster has undergone a recent, violent merger. The spectral analysis shows that the SE component is consistent with being thermal. We find the 3 sigma upper limit on the non-thermal flux, F < 8e-12 erg s^{-1} cm^{-2} in the 12-60 keV band. Combining this limit with a recent discovery of the radio mini halo at 1.4 GHz, we find a lower limit on the strength of the intracluster magnetic field, B > 0.007 micro G.Comment: 15 pages, 13 figures. Accepted for publication in A&

Structural correlations in heterogeneous electron transfer at monolayer and multilayer graphene electrodes

As a new form of carbon, graphene is attracting intense interest as an electrode material with widespread applications. In the present study, the heterogeneous electron transfer (ET) activity of graphene is investigated using scanning electrochemical cell microscopy (SECCM), which allows electrochemical currents to be mapped at high spatial resolution across a surface for correlation with the corresponding structure and properties of the graphene surface. We establish that the rate of heterogeneous ET at graphene increases systematically with the number of graphene layers, and show that the stacking in multilayers also has a subtle influence on ET kinetics. © 2012 American Chemical Society

Suzaku measurement of Abell 2204's intracluster gas temperature profile out to 1800 kpc

Context: Measurements of intracluster gas temperatures out to large radii are important for the use of clusters for precision cosmology and for studies of cluster physics. Previous attempts to measure robust temperatures at cluster virial radii failed. Aims: The goal of this work is to measure the temperature profile of the very relaxed galaxy cluster Abell 2204 out to large radii, possibly reaching the virial radius. Methods: Taking advantage of its low particle background due to its low-Earth orbit, Suzaku data are used to measure the outer temperature profile of Abell 2204. These data are combined with Chandra and XMM-Newton data of the same cluster in order to make the connection to the inner regions, unresolved by Suzaku, and to determine the smearing due to Suzaku's PSF. Results: The temperature profile of Abell 2204 is determined from 10 kpc to 1800 kpc, close to an estimate of r200 (the approximation to the virial radius). The temperature rises steeply from below 4 keV in the very center up to more than 8 keV in the intermediate range and then decreases again to about 4 keV at the largest radii. Varying the measured particle background normalization artificially by +-10 percent does not change the results significantly. Predictions for outer temperature profiles based on hydrodynamic simulations show good agreement. In particular, we find the observed temperature profile to be slightly steeper but consistent with a drop of a factor of 0.6 from 0.3 r200 to r200, as predicted by simulations. Conclusions: Temperature measurements up to the virial radius seem feasible with Suzaku, when a careful analysis of the different background components and the effects of the PSF is performed. The result obtained here indicates that numerical simulations capture the intracluster gas physics well in cluster outskirts.Comment: 7 pages; Astronomy and Astrophysics, accepted; additional systematic effects have been quantified, results unchanged; also available at http://www.reiprich.ne

Unique Signature of Dark Matter in Ancient Mica

Mica can store (for >1 Gy) etchable tracks caused by atoms recoiling from WIMPs. Because a background from fission neutrons will eventually limit this technique, a unique signature for WIMPs in ancient mica is needed. Our motion around the center of the Galaxy causes WIMPs, unlike neutrons, to enter the mica from a preferred direction on the sky. Mica is a directional detector and despite the complex rotations that natural mica crystals make with respect to this WIMP ``wind,'' there is a substantial dependence of etch pit density on present day mica orientation.Comment: 5 pages, LaTeX, 2 figures. Accepted for publication at Phys. Rev. Let

The Imprint of Galaxy Formation on X-ray Clusters

It is widely believed that structure in the Universe evolves hierarchically, as primordial density fluctuations, amplified by gravity, collapse and merge to form progressively larger systems. The structure and evolution of X-ray clusters, however, seems at odds with this hierarchical scenario for structure formation. Poor clusters and groups, as well as most distant clusters detected to date, are substantially fainter than expected from the tight relations between luminosity, temperature and redshift predicted by these models. Here we show that these discrepancies arise because, near the centre, the entropy of the hot, diffuse intracluster medium (ICM) is higher tha$achievable through gravitational collapse, indicating substantial non-gravitational heating of the ICM. We estimate this excess entropy for the first time, and argue that it represents a relic of the energetic winds through which forming galaxies polluted the ICM with metals. Energetically, this is onl$ possible if the ICM is heated at modest redshift (z \ltsim 2) but prior to cluster collapse, indicating that the formation of galaxies precedes that of clusters and that most clusters have been assembled very recently.Comment: 5 pages, plus 2 postscript figures (one in colour), accepted for publication in Natur