Persistent clinical efficacy and safety of anti-tumour necrosis factor \textgreeka therapy with infliximab in patients with ankylosing spondylitis over 5 years: evidence for different types of response

Background: There is insufficient evidence for the long-term efficacy and safety of anti-tumour necrosis factor therapy in patients with ankylosing spondylitis (AS). This is the first report on the treatment with infliximab over 5 years.Methods: As part of a multicentre randomised trial, 69 patients with active AS at baseline (BL) have been continuously treated with infliximab (5 mg/kg i.v. every 6 weeks)---except for a short discontinuation after 3 years (FU1). The primary outcome of this extension was remission according to the ASsessment in Ankylosing Spondylitis (ASAS) criteria at the end of year 5 of the study (FU2).Results: Of the 43 patients who completed year 3, 42 agreed to continue, 38 of which (90.5%) finished year 5 (55% of 69 initially). Partial clinical remission was achieved in 13 of 38 patients (34.2%) at FU1 and FU2. At FU2, the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was 2.5±1.9 (BL:6.4, FU1:2.5). BASDAI values <4 were seen in 79% of patients at both, FU1 and FU2. ASAS 20% and 40% responses were seen in 32 (84%) and 24 (63%) patients at FU2, respectively. Most patients classified as non-responders at FU2 were part-time responders, as all but one patient achieved an ASAS 20% response at least once within the last 2 years. Three types of responders were identified. No major side effects occurred during years 4 and 5 of infliximab therapy.Conclusions: Infliximab is safe and efficacious in AS patients over 5 years. The majority of the patients remained on treatment and had rather persistent levels of low disease activity. Different response types could be identified

Hubble Tarantula Treasury Project: Unraveling Tarantula's Web. II. Optical and Near Infrared Star Formation History of the Starburst Cluster NGC 2070 in 30 Doradus

We present a study of the recent star formation of 30 Doradus in the Large Magellanic Cloud (LMC) using the panchromatic imaging survey Hubble Tarantula Treasury Project (HTTP). In this paper we focus on the stars within 20 pc of the center of the massive ionizing cluster of 30 Doradus, NGC 2070. We recovered the star formation history by comparing deep optical and NIR color-magnitude diagrams (CMDs) with state-of-the-art synthetic CMDs generated with the latest PARSEC models, which include all stellar phases from pre-main sequence to post- main sequence. For the first time in this region we are able to measure the star formation using intermediate and low mass stars simultaneously. Our results suggest that NGC2070 experienced a prolonged activity. In particular, we find that the star formation in the region: i) exceeded the average LMC rate ~ 20 Myr ago; ii) accelerated dramatically ~ 7 Myr ago; and iii) reached a peak value 1-3 Myr ago. We did not find significant deviations from a Kroupa initial mass function down to 0.5 Msun. The average internal reddening E(B-V) is found to be between 0.3 and 0.4 mag.Comment: Submitted to Ap

An appraisal of the influence of the metabotropic glutamate 5 (mglu5) receptor on sociability and anxiety

Amongst the many neurotransmitter systems causally linked to the expression of social behavior, glutamate appears to play a pivotal role. In particular, metabotropic glutamate 5 (mGlu5) receptors have received much attention as its altered function has been reported in several mouse models of autism spectrum disorders and mental retardation. Inhibition of the activity of mGlu5 receptors by means of genetic or pharmacological manipulations improved social deficits in some of these animal models. However, in normal wild-type (WT) mice, pharmacological blockade of mGlu5 receptors yielded inconsistent results. The aim of our study was to investigate the actual contribution of decreased or absent mGlu5 receptor function in sociability and anxiety-like behavior as well as to explore the impact of mGlu5 receptor ablation on the pattern of brain activation upon social exposure. Here we show that Grm5-/- mice display higher social preference indexes compared to age-matched WT mice in the three-chambered social task. However, this effect was accompanied by a decreased exploratory activity during the test and increased anxiety-like behavior. Contrary to mGlu5 receptor ablation, the mGlu5 receptor negative allosteric modulator 3-((2-methyl-1,4-thiazolyl)ethynyl)pyridine (MTEP) induced anxiolytic effects without affecting social preference in WT mice. By mapping c-Fos expression in 21 different brain regions known to be involved in social interaction, we detected a specific activation of the prefrontal cortex and dorsolateral septum in Grm5-/- mice following social interaction. C-Fos expression correlation-based network and graph theoretical analyses further suggested dysfunctional connectivity and disruption of the functional brain network generated during social interaction in Grm5-/- mice. The lack of mGlu5 receptors resulted in profound rearrangements of the functional impact of prefrontal and hippocampal regions in the social interaction network. In conclusion, this work reveals a complex contribution of mGlu5 receptors in sociability and anxiety and points to the importance of these receptors in regulating brain functional connectivity during social interaction

A theory of intense-field dynamic alignment and high harmonic generation from coherently rotating molecules and interpretation of intense-field ultrafast pump-probe experiments

A theory of ultra-fast pump-probe experiments proposed by us earlier [F.H.M. Faisal et al., Phys. Rev. Lett. 98, 143001 (2007) and F.H.M. Faisal and A. Abdurrouf, Phys. Rev. Lett. 100, 123005 (2008)] is developed here fully and applied to investigate the phenomena of dynamic alignment and high harmonic generation (HHG) from coherently rotating linear molecules. The theory provides essentially analytical results for the signals that allow us to investigate the simultaneous dependence of the HHG signals on the two externally available control parameters, namely, the relative angle between the polarizations, and the delay-time between the two pulses. It is applied to investigate the characteristics of high harmonic emission from nitrogen and oxygen molecules that have been observed experimentally in a number of laboratories. The results obtained both in the time-domain and in the frequency-domain are compared with the observed characteristics as well as directly with the data and are found to agree remarkably well. In addition we have predicted the existence of a "magic" polarization angle at which all modulations of the harmonic emission from nitrogen molecule changes to a steady emission at the harmonic frequency. Among other things we have also shown a correlation between the existence of the "magic" or critical polarization angles and the symmetry of the active molecular orbitals, that is deemed to be useful in connection with the "inverse problem" of molecular imaging from the HHG data.Comment: 31 pages, 22 figures, and 140 equation

Four conjectures in Nonlinear Analysis

In this chapter, I formulate four challenging conjectures in Nonlinear Analysis. More precisely: a conjecture on the Monge-Amp\`ere equation; a conjecture on an eigenvalue problem; a conjecture on a non-local problem; a conjecture on disconnectedness versus infinitely many solutions.Comment: arXiv admin note: text overlap with arXiv:1504.01010, arXiv:1409.5919, arXiv:1612.0819

An Iterative Method Based on Fractional Derivatives for Solving Nonlinear Equations

The theory of fractional order derivatives are almost as old as the integer-order [5]. There are many applications, for example in physics [1], [2], [6], finance [8], [9] or biology [3]. Our aim is not to use fractional order operators to modeling such things, we only will use them as a device to prove a theoretical mathematical statement. In this work our goal is to find a solution numerically for the equation A(u) = f . If we assume that u is time-dependent, then one can do this by finding a stationary solution of the equation ¶tu(t)

The Newtonian Limit for Asymptotically Flat Solutions of the Vlasov-Einstein System

It is shown that there exist families of asymptotically flat solutions of the Einstein equations coupled to the Vlasov equation describing a collisionless gas which have a Newtonian limit. These are sufficiently general to confirm that for this matter model as many families of this type exist as would be expected on the basis of physical intuition. A central role in the proof is played by energy estimates in unweighted Sobolev spaces for a wave equation satisfied by the second fundamental form of a maximal foliation.Comment: 24 pages, plain TE

The structure of fluid trifluoromethane and methylfluoride

We present hard X-ray and neutron diffraction measurements on the polar fluorocarbons HCF3 and H3CF under supercritical conditions and for a range of molecular densities spanning about a factor of ten. The Levesque-Weiss-Reatto inversion scheme has been used to deduce the site-site potentials underlying the measured partial pair distribution functions. The orientational correlations between adjacent fluorocarbon molecules -- which are characterized by quite large dipole moments but no tendency to form hydrogen bonds -- are small compared to a highly polar system like fluid hydrogen chloride. In fact, the orientational correlations in HCF3 and H3CF are found to be nearly as small as those of fluid CF4, a fluorocarbon with no dipole moment.Comment: 11 pages, 9 figure

Hubble Tarantula Treasury Project. III. Photometric Catalog and Resulting Constraints on the Progression of Star Formation in the 30 Doradus Region

We present and describe the astro-photometric catalog of more than 800,000 sources found in the Hubble Tarantula Treasury Project (HTTP). HTTP is a Hubble Space Telescope (HST) Treasury program designed to image the entire 30 Doradus region down to the sub-solar (~0.5 solar masses) mass regime using the Wide Field Camera 3 (WFC3) and the Advanced Camera for Surveys (ACS). We observed 30 Doradus in the near ultraviolet (F275W, F336W), optical (F555W, F658N, F775W), and near infrared (F110W, F160W) wavelengths. The stellar photometry was measured using point-spread function (PSF) fitting across all the bands simultaneously. The relative astrometric accuracy of the catalog is 0.4 mas. The astro-photometric catalog, results from artificial star experiments and the mosaics for all the filters are available for download. Color-magnitude diagrams are presented showing the spatial distributions and ages of stars within 30 Dor as well as in the surrounding fields. HTTP provides the first rich and statistically significant sample of intermediate and low mass pre-main sequence candidates and allows us to trace how star formation has been developing through the region. The depth and high spatial resolution of our analysis highlight the dual role of stellar feedback in quenching and triggering star formation on the giant HII region scale. Our results are consistent with stellar sub-clustering in a partially filled gaseous nebula that is offset towards our side of the Large Magellanic Cloud.Comment: 20 pages, 22 Figures, 3 Tables, Photometric Catalogs and Mosaiced images will be available for download upon publication, accepted for publication on ApJ