Thalidomide: Focus on its employment in rheumatologic diseases

Thalidomide is an immunomodulatory agent; although its mechanisms of action are not fully understood, many authors have described its anti-inflammatory and immunosuppressive properties. More interestingly, thalidomide has shown the ability to suppress tumor necrosis factor alpha (TNFα) production and to modify the expression of TNFα induced adhesion molecules on endothelial cells and on human leukocytes. Thalidomide has been used in several diseases (i.e. dermatological, autoimmune, gastrointestinal). In this review we focus specifically on the use of this drug in disorders with rheumatological features such as lupus erythematosus, rheumatoid arthritis and Still's disease, ankylosing spondylitis, and Behçet's disease. Despite its well known side effects, first of all peripheral nerve involvement and teratogenesis, which can be avoided by following strict guidelines, thalidomide could represent an alternative drug in some rheumatological conditions, particularly in patients who show resistance, contraindication or toxicity with other conventional treatments

Discovery of a rich proto-cluster at z=2.9 and associated diffuse cold gas in the VIMOS Ultra-Deep Survey (VUDS)

[Abridged] We characterise a massive proto-cluster at z=2.895 that we found in the COSMOS field using the spectroscopic sample of the VIMOS Ultra-Deep Survey (VUDS). This is one of the rare structures at z~3 not identified around AGNs or radio galaxies, so it is an ideal laboratory to study galaxy formation in dense environments. The structure comprises 12 galaxies with secure spectroscopic redshift in an area of 7'x8', in a z bin of Dz=0.016. The measured galaxy number overdensity is delta_g=12+/-2. This overdensity has total mass of M~8.1x10^(14)M_sun in a volume of 13x15x17 Mpc^3. Simulations indicate that such an overdensity at z~2.9 is a proto-cluster that will collapse in a cluster of total mass M~2.5x10^(15)M_sun at z=0. We compare the properties of the galaxies within the overdensity with a control sample at the same z but outside the overdensity. We did not find any statistically significant difference between the properties (stellar mass, SFR, sSFR, NUV-r, r-K) of the galaxies inside and outside the overdensity. The stacked spectrum of galaxies in the overdensity background shows a significant absorption feature at the wavelength of Lya redshifted at z=2.895 (lambda=4736 A), with a rest frame EW = 4+/- 1.4 A. Stacking only background galaxies without intervening sources at z~2.9 along their line of sight, we find that this absorption feature has a rest frame EW of 10.8+/-3.7 A, with a detection S/N of ~4. These EW values imply a high column density (N(HI)~3-20x10^(19)cm^(-2)), consistent with a scenario where such absorption is due to intervening cold gas streams, falling into the halo potential wells of the proto-cluster galaxies. However, we cannot exclude the hypothesis that this absorption is due to the diffuse gas within the overdensity.Comment: 15 pages, 9 figures, accepted for publication in A&A (revised version after referee's comments and language editing

The Lyman Continuum escape fraction of galaxies at z=3.3 in the VUDS-LBC/COSMOS field

The Lyman continuum (LyC) flux escaping from high-z galaxies into the IGM is a fundamental quantity to understand the physical processes involved in the reionization epoch. We have investigated a sample of star-forming galaxies at z~3.3 in order to search for possible detections of LyC photons escaping from galaxy halos. UV deep imaging in the COSMOS field obtained with the prime focus camera LBC at the LBT telescope was used together with a catalog of spectroscopic redshifts obtained by the VIMOS Ultra Deep Survey (VUDS) to build a sample of 45 galaxies at z~3.3 with L>0.5L*. We obtained deep LBC images of galaxies with spectroscopic redshifts in the interval 3.27<z<3.40 both in the R and deep U bands. A sub-sample of 10 galaxies apparently shows escape fractions>28% but a detailed analysis of their properties reveals that, with the exception of two marginal detections (S/N~2) in the U band, all the other 8 galaxies are most likely contaminated by the UV flux of low-z interlopers located close to the high-z targets. The average escape fraction derived from the stacking of the cleaned sample was constrained to fesc_rel<2%. The implied HI photo-ionization rate is a factor two lower than that needed to keep the IGM ionized at z~3, as observed in the Lyman forest of high-z QSO spectra or by the proximity effect. These results support a scenario where high redshift, relatively bright (L>0.5L*) star-forming galaxies alone are unable to sustain the level of ionization observed in the cosmic IGM at z~3. Star-forming galaxies at higher redshift and at fainter luminosities (L<<L*) can be the major contributors to the reionization of the Universe only if their physical properties are subject to rapid changes from z~3 to z~6-10. Alternatively, ionizing sources could be discovered looking for fainter sources among the AGN population at high-z.Comment: 21 pages, 9 figures. Accepted for publication in A&

The VIMOS Ultra Deep Survey First Data Release: spectra and spectroscopic redshifts of 698 objects up to z~6 in CANDELS

This paper describes the first data release (DR1) of the VIMOS Ultra Deep Survey (VUDS). The DR1 includes all low-resolution spectroscopic data obtained in 276.9 arcmin2 of the CANDELS-COSMOS and CANDELS-ECFDS survey areas, including accurate spectroscopic redshifts z_spec and individual spectra obtained with VIMOS on the ESO-VLT. A total of 698 objects have a measured redshift, with 677 galaxies, two type-I AGN and a small number of 19 contaminating stars. The targets of the spectroscopic survey are selected primarily on the basis of their photometric redshifts to ensure a broad population coverage. About 500 galaxies have z_spec>2, 48 with z_spec>4, and the highest reliable redshifts reach beyond z_spec=6. This dataset approximately doubles the number of galaxies with spectroscopic redshifts at z>3 in these fields. We discuss the general properties of the sample in terms of the spectroscopic redshift distribution, the distribution of Lyman-alpha equivalent widths, and physical properties including stellar masses M_star and star formation rates (SFR) derived from spectral energy distribution fitting with the knowledge of z_spec. We highlight the properties of the most massive star-forming galaxies, noting the large range in spectral properties, with Lyman-alpha in emission or in absorption, and in imaging properties with compact, multi-component or pair morphologies. We present the catalogue database and data products. All data are publicly available and can be retrieved from a dedicated query-based database available at http://cesam.lam.fr/vuds.Comment: 11 pages, 6 figures, submitted to A&

Web of the giant: Spectroscopic confirmation of a large-scale structure around the z = 6.31 quasar SDSS J1030+0524

We report on the spectroscopic confirmation of a large-scale structure around the luminous z = 6.31 quasi-stellar object (QSO) SDSS J1030+0524, powered by a one billion solar mass black hole. The structure is populated by at least six members, namely, four Lyman-break galaxies (LBGs), and two Lyman alpha emitters (LAEs). The four LBGs were identified among a sample of 21 i-band dropouts with zAB &lt; 25.5 selected up to projected separations of 5 physical Mpc (15 arcmin) from the QSO. Their redshifts were determined through multi-object spectroscopic observations at 8-10 m class telescopes lasting up to eight hours. The two LAEs were identified in a 6 h VLT/MUSE observation centered on the QSO. The redshifts of the six galaxies cover the range between 6.129-6.355. Assuming that the peculiar velocities are negligible, this range corresponds to radial separations of \ub15 physical Mpc from the QSO, that is comparable to the projected scale of the observed LBG distribution on the sky. We conservatively estimate that this structure is significant at a level &gt; 3.5\u3c3 and that the level of the galaxy overdensity is at least 1.5-2 within the large volume sampled ( 3c780 physical Mpc3). The spectral properties of the six member galaxies (Ly\u3b1 strength and UV luminosity) are similar to those of field galaxies at similar redshifts. This is the first spectroscopic identification of a galaxy overdensity around a supermassive black hole in the first billion years of the Universe. Our finding lends support to the idea that the most distant and massive black holes form and grow within massive (&gt;1012 M) dark matter halos in large-scale structures and that the absence of earlier detections of such systems is likely due to observational limitations

The Reflective Teaching Log (RTL): Effective Documentation of Participatory Teaching Requirements

© 2019, The Author(s). We created a reflective teaching log for a student-as-teacher elective to track students’ required participatory teaching and to provide a mechanism for reflective evaluation. This Minute Paper–based log is easy to use and can be adapted to similar programs capturing insights of students’ teaching experiences and supports reflective learning

Realistic Simulation of Neuronal Activity:A Contribution to the Debate on Direct Detection of Neuronal-Currents by MRI

Many efforts have been done in order to preview the properties of the magnetic resonance (MR) signals produced by the neuronal currents using simulations. In this paper, starting with a detailed calculation of the magnetic field produced by the neuronal currents propagating over single hippocampal CA1 pyramidal neurons placed inside a cubic MR voxel of length 1.2 mm, we proceeded on the estimation of the phase and magnitude MR signals. We then extended the results to layers of parallel and synchronous similar neurons and to ensembles of layers, considering different echo times, voxel volumes and neuronal densities. The descriptions of the neurons and of their electrical activity took into account the real neuronal morphologies and the physiology of the neuronal events. Our results concern: (a) the expected time course of the MR signals produced by the neuronal currents in the brain, based on physiological and anatomical properties; (b) the different contributions of post-synaptic potentials and of action potentials to the MR signals; (c) the estimation of the equivalent current dipole and the influence of its orientation with respect to the external magnetic field on the observable MR signal variations; (d) the size of the estimated neuronal current induced phase and magnitude MR signal changes with respect to the echo time, voxel-size and neuronal density. The inclusion of realistic neuronal properties into the simulation introduces new information that can be helpful for the design of MR sequences for the direct detection of neuronal current effects and the testing of bio-electromagnetic models

Peripheral Nerve Stimulation in MRI: Insights from a three level analysis and coupled EM-electrophysiological simulations in neuro-functionalized human models

The mechanisms of peripheral nerve stimulation (PNS) induced by the fast switching of MRI gradient coils are only partially understood, stimulation sites and E-field (or dB/dt) thresholds show large inter-subject variability and neurostimulation models based on the amphibian SENN axon model are not ideal. We propose a 3 level computational investigation that combines analysis of E-field exposure, of activation functions, and of multi-parametric EM-electrophysiological simulations in neuro-functionalized human models for different axon models and gradient waveforms. Results concerning E-field/dB/dt thresholds values and sites of neurostimulation are compared with published experimental data. A functional uncertainty analysis is also provided

Very early prenatal diagnosis of Cockayne’s syndrome by coelocentesis

Cockayne’s syndrome (CS) is a rare autosomal recessive multisystem disease characterised by early severe progression of symptoms. This study reports the feasibility of earlier prenatal diagnosis of CS by coelocentesis at 8 weeks of gestation respect to amniocentesis or villocentesis. Three couples at risk for CS asked to perform prenatal diagnosis by coelocentesis. Coelomic fluid was aspired from coelomic cavity in four singleton pregnancy at 8&nbsp;weeks of gestation and 40 foetal cells were recovered by micromanipulator. Maternal DNA contamination was evaluated by quantitative fluorescent PCR (QF-PCR) and target regions of foetal DNA containing parental mutations of ERCC6 gene were amplified and sequenced. In all these cases, molecular analysis was possible. One foetus resulted affected of CS and the diagnosis was confirmed on placental tissue after voluntary abortion. In three cases, foetuses resulted carrier of a parental mutation and the results were confirmed after the birth. This study suggests that reliable prenatal diagnosis of CS could be performed using foetal cells present in coelomatic fluid in earlier pregnancy. Coelocentesis could be applied in prenatal diagnosis of CSs as well as for other monogenic diseases, at very early stage of pregnancy, if parental mutations are already known.Impact StatementWhat is already know on this subject? Previous studies utilising coelocentesis for prenatal determination of foetal sex reported variable success ranging from 58% to 95%, because of low total DNA content and presence of maternal cell contamination. This procedure has never been reported for early prenatal diagnosis at 8 weeks of gestation for rare genetically transmitted diseases such as Cockayne’s syndrome. What do the results of this study add? This study demonstrates that coelomic fluid sampling combined with well-standardised laboratory procedures can be applied for prenatal diagnosis at eight weeks of gestation for any rare monogenic disease if molecular defects are known. What are the implications of these findings for clinical practice and/or further research? The findings of this study in at risk couples for monogenic diseases investigated by coelocentesis demonstrate that embryo-foetal cell selection from CF allows reliable and early prenatal diagnosis of diseases. This technique is attractive to parents because it provides prenatal diagnosis of genetic disease at least 4 weeks earlier than what can be achieved by the traditional procedures reducing anxiety of parents and provides the option for medical termination of affected cases at 8–10 weeks’ gestation, which is less traumatic and safer than second-trimester surgical termination. Further research concerns the possibility to obtain foetal karyotype at eight weeks of gestation and the possibility of intrauterine corrective therapy