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Biological disease-modifying anti-rheumatic drugs (bDMARDs) are recommended for radiographic axial spondyloarthritis, otherwise known as ankylosing spondylitis, when conventional therapies are not effective. We report efficacy and safety data on ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A (IL-17A), in patients with radiographic axial spondyloarthritis who have not previously been treated with bDMARDs. In this phase 3, randomised, double-blind, placebo-controlled superiority study of ixekizumab, adult patients with inadequate response or intolerance to non-steroidal anti-inflammatory drugs, an established diagnosis of radiographic axial spondyloarthritis, radiographic sacroiliitis centrally defined by modified New York criteria, and at least one spondyloarthritis feature according to the Assessment of SpondyloArthritis international Society (ASAS) criteria, were recruited from 84 sites (12 countries) in Europe, Asia, and North America. By use of a computer-generated random sequence, patients were randomly assigned (1:1:1:1) to 80 mg subcutaneous ixekizumab every two (Q2W) or four (Q4W) weeks, 40 mg adalimumab Q2W (active reference group), or placebo. The primary objective was to compare the proportion of patients achieving an ASAS40 response, a composite measure of clinical improvement in axial spondyloarthritis, at week 16 for both ixekizumab treatment groups versus the placebo group. The adalimumab reference group was included as an in-study active reference for comparison with placebo to provide additional context to interpretation of the ixekizumab study results. Between June 20, 2016, and Aug 22, 2017, 341 patients were randomly assigned to either the placebo group (n=87), adalimumab group (n=90), ixekizumab Q2W (n=83), or ixekizumab Q4W (n=81). At week 16, compared with placebo (16 [18%] of 87), more patients achieved ASAS40 with ixekizumab Q2W (43 [52%] of 83; p<0·0001), ixekizumab Q4W (39 [48%] of 81; p<0·0001), and adalimumab (32 [36%] of 90; p=0·0053). One serious infection occurred in each of the ixekizumab Q2W (1%), ixekizumab Q4W (1%), and adalimumab (1%) groups; none were reported with placebo. One (1%) Candida infection occurred in the adalimumab group and one (1%) patient receiving ixekizumab Q2W was adjudicated as having probable Crohn's disease. No treatment-emergent opportunistic infections, malignancies, or deaths occurred. Each dosing regimen of ixekizumab was superior to placebo for improving radiographic axial spondyloarthritis signs and symptoms in patients not previously treated with bDMARDs; the safety profile was consistent with previous indications of ixekizumab. Eli Lilly and Company

ObjectivesThe objective of COAST-Y was to evaluate the effect of continuing versus withdrawing ixekizumab (IXE) in patients with axial spondyloarthritis (axSpA) who had achieved remission.MethodsCOAST-Y is an ongoing, phase III, long-term extension study that included a double-blind, placebo (PBO)-controlled, randomised withdrawal-retreatment period (RWRP). Patients who completed the originating 52-week COAST-V, COAST-W or COAST-X studies entered a 24-week lead-in period and continued either 80 mg IXE every 2 (Q2W) or 4 weeks (Q4W). Patients who achieved remission (an Ankylosing Spondylitis Disease Activity Score (ASDAS)<1.3 at least once at week 16 or week 20, and <2.1 at both visits) were randomly assigned equally at week 24 to continue IXE Q4W, IXE Q2W or withdraw to PBO in a blinded fashion. The primary endpoint was the proportion of flare-free patients (flare: ASDAS≥2.1 at two consecutive visits or ASDAS>3.5 at any visit) after the 40-week RWRP, with time-to-flare as a major secondary endpoint.ResultsOf 773 enrolled patients, 741 completed the 24-week lead-in period and 155 entered the RWRP. Forty weeks after randomised withdrawal, 83.3% of patients in the combined IXE (85/102, p<0.001), IXE Q4W (40/48, p=0.003) and IXE Q2W (45/54, p=0.001) groups remained flare-free versus 54.7% in the PBO group (29/53). Continuing IXE significantly delayed time-to-flare versus PBO, with most patients remaining flare-free for up to 20 weeks after IXE withdrawal.ConclusionsPatients with axSpA who continued treatment with IXE were significantly less likely to flare and had significantly delayed time-to-flare compared with patients who withdrew to PBO.

We present results from a large scale R-band survey of the nearby Leo I group to measure the luminosity function down to dwarf spheroidal luminosities and surface brightnesses. This program has utilized>7 square degrees of imaging with the Mosaic camera at the KPNO 0.9mand extensive, on-going spectroscopic follow-up. We estimate our completeness from simulations to be 90% at μ^sub R^(0) 24.5, M^sub R^ -11.Leo I is a nearby, low-density group for which a steep faint-end slope has been suggested (Ferguson and Sandage, 1991).We find the luminosity function to be more similar to that of the Local Group at the faint-end (flat).We also find an unusual gap in the luminosity function at intermediate luminosities, -19.5 < M^sub R^ < -16. This gap cannot be explained by pure Poisson fluctuations around a typical Schechter function, nor is it likely to result from photometric incompleteness.[PUBLICATION ABSTRACT]

This dissertation presents the results of an extensive survey of the Leo I group down to MR ∼ −10 dwarf galaxies. This survey is part of a larger effort to measure the faint-end of the galaxy luminosity function in poor groups to faint limiting magnitudes and surface brightnesses. With the KPNO 0.9m+Mosaic we have surveyed over 7 square degrees in the R-band in the Leo I group at 10 Mpc. We have developed a detection method where we complement the standard, thresholding detection procedure with a matched filter technique optimized to enhance low surface brightness features and detect diffuse dwarf galaxies at a distance of 10 Mpc. Our photometric catalog includes morphological membership selection, guided by a representative sample of follow-up distance measurements from redshifts as well as I-band surface-brightness fluctuations of our most diffuse dwarf candidates. We further quantify our selection effects as a function of total R-band magnitude and central surface brightness with extensive Monte Carlo simulations. The resulting selection function we apply to our final luminosity function, weighting each galaxy by its ability to be detected. We find that at the 90% detection limit, we can detect dwarf galaxies similar to Antlia and Sculptor, and at the 50% detection level, dwarfs similar to Tucana and Leo II. While our method is optimized to find Local-Group-like dwarfs, we also find unusual objects not seen in Local Group. Among our confirmed group members are large scale-length, LSB dwarfs like those seen in Virgo (Impey et al. 1988, ApJ, 330, 634), as well as unusually compact, higher surface brightness dwarfs similar to the recently identified Ultra-Compact Dwarfs (UCDs) of Fornax (Phillipps et al., 2001, ApJ, 560, 201). These objects do not fall on the Local Group magnitude-surface brightness relation, and suggest that using this relation to guide morphological membership classification selects against such unusual objects. From our sub-sample of follow-up observations, we find that 50% of our μ0 > 22 objects are bona fide members, and 11% of our μ0 ≤ 22 objects are members. The majority of back-ground interlopers in our sample are very nearby ( v < 20, 000 km s−1 ). This fact, coupled with the unexpected object types we find, indicates we require a massive amount of follow-up observations to determine membership for each galaxy individually. With our current data, we measure a faint-end slope for our completeness-corrected luminosity function of α = −1.02 ± 0.02. If we further correct this for membership completeness as a function of surface brightness, we find a somewhat steeper slope of α = −1.17 ± 0.04. Both of these slopes are rather flat and generally consistent with those measured in the Local Group and other poor groups. We also confirm an unusual gap in the Leo I luminosity function −19.5 < MR < −16 where there appear to be no intermediate luminosity galaxies in Leo I. The presence of UCDs in Leo I, which fall off the high surface brightness, low luminosity envelope of the Local Group's magnitude-surface brightness relation, might indicate a larger population of previously overlooked compact, exponential-profile dwarfs that could contribute significantly to the faint end of the luminosity function.

Far from being anti-democratic, as Prime Minister Stephen Harper would have us believe, Her Excellency's power to give another party or the coalition the opportunity to govern has long been a part of our parliamentary tradition. Canada already tried a coalition government in 1917, with good results, and Harper himself argued for a coalition government including the Tories, the NDP and the Bloc Quebecois in 2004 when he was in opposition.

We present the data processing and analysis techniques we are using to determine structural and photometric properties of galaxies in our Gemini/HST Galaxy Cluster Project sample. The goal of this study is to understand cluster galaxy evolution in terms of scaling relations and structural properties of cluster galaxies at redshifts 0.15 < z < 1.0. To derive parameters such as total magnitude, half-light radius, effective surface brightness, and Sersic n, we fit r^{1/4} law and Sersic function 2-D surface brightness profiles to each of the galaxies in our sample. Using simulated galaxies, we test how the assumed profile affects the derived parameters and how the uncertainties affect our Fundamental Plane results. We find that while fitting galaxies which have Sersic index n < 4 with r^{1/4} law profiles systematically overestimates the galaxy radius and flux, the combination of profile parameters that enter the Fundamental Plane has uncertainties that are small. Average systematic offsets and associated random uncertainties in magnitude and log r_e for n > 2 galaxies fitted with r^{1/4} law profiles are -0.1+-0.3 and 0.1+-0.2 respectively. The combination of effective radius and surface brightness, log r_e - \\beta log _e, that enters the Fundamental Plane produces offsets smaller than -0.02+-0.10. This systematic error is insignificant and independent of galaxy magnitude or size. A catalog of photometry and surface brightness profile parameters is presented for three of the clusters in our sample, RX J0142.0+2131, RX J0152.7-1357, and RX J1226.9+3332 at redshifts 0.28, 0.83, and 0.89 respectively.

We present the Fundamental Plane (FP) for 38 early-type galaxies in the two rich galaxy clusters RXJ0152.7-1357 (z=0.83) and RXJ1226.9+3332 (z=0.89), reaching a limiting magnitude of M_B =-19.8 mag in the rest frame of the clusters. While the zero point offset of the FP for these high redshift clusters relative to our low redshift sample is consistent with passive evolution with a formation redshift of z_form ~ 3.2, the FP for the high redshift clusters is not only shifted as expected for a mass-independent z_form, but rotated relative to the low redshift sample. Expressed as a relation between the galaxy masses and the mass-to-light ratios the FP is significantly steeper for the high redshift clusters than found at low redshift. We interpret this as a mass dependency of the star formation history, as has been suggested by other recent studies. The low mass galaxies (10^10.3 M_sun) have experienced star formation as recently as z ~ 1.35 (1.5 Gyr prior to their look back time), while galaxies with masses larger than 10^11.3 M_sun had their last major star formation episode at z > 4.5.

We present a program to study the galaxy luminosity function (GLF) of the Leo I and Coma I Groups at ~10 Mpc. We have surveyed over seven square degrees in Leo I and ~11 square degrees in Coma I. In this paper, we detail the method we have developed and implemented for identifying on morphological grounds low-surface-brightness, M_R < -10 dwarf galaxies at a distance of 10 Mpc. We also describe extensive Montecarlo simulations of artificial galaxies which we use to tune our detection algorithms and evaluate our detection efficiency and parameter recovery as a function of mu_R(0) and R_T. We find for a sub-set of our Leo I data that at the 90% completeness level we can detect dwarfs comparable to Antlia and Sculptor. Finally, we describe preliminary follow-up observations which confirm we are detecting dwarf spheroidals in Leo I at 10 Mpc.

Purpose of Review Evidence regarding the treatment of late-life depression is not necessarily generalizable to persons with a neurocognitive disorder and comorbid depression. Thus, this article reviews recent evidence that pertains to the treatment of depression in older adults with neurocognitive disorders, and synthesizes and critically analyzes this literature to identify methodological issues and gaps for the purpose of future research. Recent Findings Controlled trials and meta-analyses examining depression treatment in neurocognitive disorders, published between 2015 and 2019 ( N  = 16 reports), can be divided into those addressing pharmacotherapy, psychological and behavioral therapy, and somatic therapy. The evidence generally does not support benefit of antidepressant medication over placebo in treating depressive disorders in dementia. No pharmacological studies since 2015 have examined antidepressant medication in participants with mild cognitive impairment (MCI). Problem adaptation therapy demonstrates efficacy for depression in MCI and mild dementia. Other psychological and behavioral interventions for depressive symptoms in dementia demonstrate mixed findings. The only somatic treatment trials published since 2015 have assessed bright light therapy, with positive findings but methodological limitations. Summary Psychological, behavioral, and somatic treatments represent promising treatment options for depression in neurocognitive disorders, but further studies are needed, particularly in participants with depressive disorders rather than subclinical depressive symptoms. Little is known about the treatment of depression in patients with MCI, and rigorous identification of MCI in late-life depression treatment trials will help to advance knowledge in this area. Addressing methodological issues, particularly the diagnosis and measurement of clinically significant depression in dementia, will help to move the field forward.