Discovery of Three Distant, Cold Brown Dwarfs in the WFC3 Infrared Spectroscopic Parallels Survey

We present the discovery of three late type (>T4) brown dwarfs, including a probable Y dwarf, in the WFC3 Infrared Spectroscopic Parallels (WISP) Survey. We use the G141 grism spectra to determine the spectral types of the dwarfs and derive distance estimates based on a comparison with nearby T dwarfs with known parallaxes. These are the most distant spectroscopically confirmed T/Y dwarfs, with the farthest at an estimated distance of ~400 pc. We compare the number of cold dwarfs found in the WISP survey with simulations of the brown dwarf mass function. The number found is generally consistent with an initial stellar mass function dN/dM \propto M^{-\alpha} with \alpha = 0.0--0.5, although the identification of a Y dwarf is somewhat surprising and may be indicative of either a flatter absolute magnitude/spectral type relation than previously reported or an upturn in the number of very late type brown dwarfs in the observed volume.Comment: Accepted for publication by ApJ Letters. 10 pages, 2 figure

Hubble Space Telescope Grism Spectroscopy of Extreme Starbursts Across Cosmic Time: The Role of Dwarf Galaxies in the Star Formation History of the Universe

Near infrared slitless spectroscopy with the Wide Field Camera 3, onboard the Hubble Space Telescope, offers a unique opportunity to study low-mass galaxy populations at high-redshift ($z\sim$1-2). While most high$-z$ surveys are biased towards massive galaxies, we are able to select sources via their emission lines that have very-faint continua. We investigate the star formation rate (SFR)-stellar mass ($M_{\star}$) relation for about 1000 emission-line galaxies identified over a wide redshift range of $0.3 \lesssim z \lesssim 2.3$. We use the H$_{\alpha}$ emission as an accurate SFR indicator and correct the broadband photometry for the strong nebular contribution to derive accurate stellar masses down to $M_{\star} \sim 10^{7} M_{\odot}$. We focus here on a subsample of galaxies that show extremely strong emission lines (EELGs) with rest-frame equivalent widths ranging from 200 to 1500 \AA. This population consists of outliers to the normal SFR-$M_{\star}$ sequence with much higher specific SFRs ($> 10$ Gyr$^{-1}$). While on-sequence galaxies follow a continuous star formation process, EELGs are thought to be caught during an extreme burst of star formation that can double their stellar mass in less than $100$ Myr. The contribution of starbursts to the total star formation density appears to be larger than what has been reported for more massive galaxies in previous studies. In the complete mass range $8.2 <$ log($M_{\star}/M_{\odot}$) $< 10$ and a SFR lower completeness limit of about 2 $M_{\odot}$ yr$^{-1}$ (10 $M_{\odot}$ yr$^{-1}$) at $z\sim1$ ($z \sim 2$), we find that starbursts having EW$_{rest}$(H$_{\alpha}$)$>$ 300, 200, and 100 A contribute up to $\sim13$, 18, and 34 %, respectively, to the total SFR of emission-line selected sample at $z\sim1-2$. The comparison with samples of massive galaxies shows an increase in the contribution of starbursts towards lower masses.Comment: 11 pages, 6 figures. The Astrophysical Journal, in pres

Physical Properties of Emission-Line Galaxies at z ~ 2 from Near-Infrared Spectroscopy with Magellan FIRE

We present results from near-infrared spectroscopy of 26 emission-line galaxies at z ~ 2 obtained with the FIRE spectrometer on the Magellan Baade telescope. The sample was selected from the WISP survey, which uses the near-infrared grism of the Hubble Space Telescope Wide Field Camera 3 to detect emission-line galaxies over 0.3 < z < 2.3. Our FIRE follow-up spectroscopy (R~5000) over 1.0-2.5 micron permits detailed measurements of physical properties of the z~2 emission-line galaxies. Dust-corrected star formation rates for the sample range from ~5-100 M_sun yr-1. We derive a median metallicity for the sample of ~0.45 Z_sun, and the estimated stellar masses range from ~10^8.5 - 10^9.5 M_sun. The average ionization parameters measured for the sample are typically much higher than what is found for local star-forming galaxies. We derive composite spectra from the FIRE sample, from which we infer typical nebular electron densities of ~100-400 cm^-3. Based on the location of the galaxies and composite spectra on BPT diagrams, we do not find evidence for significant AGN activity in the sample. Most of the galaxies as well as the composites are offset in the BPT diagram toward higher [O III]/H-beta at a given [N II]/H-alpha, in agreement with other observations of z > 1 star-forming galaxies, but composite spectra derived from the sample do not show an appreciable offset from the local star-forming sequence on the [O III]/H-beta versus [S II]/H-alpha diagram. We infer a high nitrogen-to-oxygen abundance ratio from the composite spectrum, which may contribute to the offset of the high-redshift galaxies from the local star-forming sequence in the [O III]/H-beta versus [N II]/H-alpha diagram. We speculate that the elevated nitrogen abundance could result from substantial numbers of Wolf-Rayet stars in starbursting galaxies at z~2. (Abridged)Comment: Accepted for publication in Ap

Resistance to local anesthesia in people with the Ehlers-Danlos Syndromes presenting for dental surgery

Background: People with the Ehlers-Danlos Syndromes (EDS), a group of heritable disorders of connective tissue, often report experiencing dental procedure pain despite local anesthetic (LA) use. Clinicians have been uncertain how to interpret this apparent LA resistance, as comparison of EDS and non-EDS patient experience is limited to anecdotal evidence and small case series. The primary goal of this hypothesis-generating study was to investigate the recalled adequacy of pain prevention with LA administered during dental procedures in a large cohort of people with and without EDS. A secondary exploratory aim asked people with EDS to recall comparative LA experiences. Methods: We administered an online survey through various social media platforms to people with EDS and their friends without EDS, asking about past dental procedures, LA exposures, and the adequacy of procedure pain prevention. Among EDS respondents who both received LA and recalled the specific LA used, we compared agent-specific pain prevention for lidocaine, procaine, bupivacaine, mepivacaine, and articaine. Results: Among the 980 EDS respondents who had undergone a dental procedure LA, 88% (n = 860) recalled inadequate pain prevention. Among 249 non EDS respondents only 33% (n = 83) recalled inadequate pain prevention (P < 0.001 compared to EDS respondents). The agent with the highest EDS-respondent reported success rate was articaine (30%), followed by bupivacaine (25%), and mepivacaine (22%). Conclusions: EDS survey respondents reported nearly three times the rate of LA non-response compared to non-EDS respondents, suggesting that LAs were less effective in preventing their pain associated with routine office dental procedures

Presentation and physical therapy management of upper cervical instability in patients with symptomatic generalized joint hypermobility: International expert consensus recommendations

Experts in symptomatic generalized joint hypermobility (S-GJH) agree that upper cervical instability (UCI) needs to be better recognized in S-GJH, which commonly presents in the clinic as generalized hypermobility spectrum disorder and hypermobile Ehlers-Danlos syndrome. While mild UCI may be common, it can still be impactful; though considerably less common, severe UCI can potentially be debilitating. UCI includes both atlanto-occipital and atlantoaxial instability. In the absence of research or published literature describing validated tests or prediction rules, it is not clear what signs and symptoms are most important for diagnosis of UCI. Similarly, healthcare providers lack agreed-upon ways to screen and classify different types or severity of UCI and how to manage UCI in this population. Consequently, recognition and management of UCI in this population has likely been inconsistent and not based on the knowledge and skills of the most experienced clinicians. The current work represents efforts of an international team of physical/physiotherapy clinicians and a S-GJH expert rheumatologist to develop expert consensus recommendations for screening, assessing, and managing patients with UCI associated with S-GJH. Hopefully these recommendations can improve overall recognition and care for this population by combining expertise from physical/physiotherapy clinicians and researchers spanning three continents. These recommendations may also stimulate more research into recognition and conservative care for this complex condition

The quality of different types of child care at 10 and 18 months. A comparison between types and factors related to quality.

The quality of care offered in four different types of non-parental child care to 307 infants at 10 months old and 331 infants at 18 months old was compared and factors associated with higher quality were identified. Observed quality was lowest in nurseries at each age point, except that at 18 months they offered more learning activities. There were few differences in the observed quality of care by child-minders, grandparents and nannies, although grandparents had somewhat lower safety and health scores and offered children fewer activities. Cost was largely unrelated to quality of care except in child-minding, where higher cost was associated with higher quality. Observed ratios of children to adults had a significant impact on quality of nursery care; the more infants or toddlers each adult had to care for, the lower the quality of the care she gave them. Mothers' overall satisfaction with their child's care was positively associated with its quality for home-based care but not for nursery settings

Low Masses and High Redshifts: The Evolution of the Mass-Metallicity Relation

We present the first robust measurement of the high redshift mass-metallicity (MZ) relation at 10^8 ≾ M/M_☉ ≾ 10^(10), obtained by stacking spectra of 83 emission-line galaxies with secure redshifts between 1.3 ≾ z ≾ 2.3. For these redshifts, infrared grism spectroscopy with the Hubble Space Telescope Wide Field Camera 3 is sensitive to the R_(23) metallicity diagnostic: ([O II] λλ3726, 3729 + [O III] λλ4959, 5007)/Hβ. Using spectra stacked in four mass quartiles, we find a MZ relation that declines significantly with decreasing mass, extending from 12+log(O/H) = 8.8 at M = 10^(9.8) M_☉, to 12+log(O/H) = 8.2 at M = 10^(8.2) M_☉. After correcting for systematic offsets between metallicity indicators, we compare our MZ relation to measurements from the stacked spectra of galaxies with M ≳ 10^(9.5) M_☉ and z ~ 2.3. Within the statistical uncertainties, our MZ relation agrees with the z ~ 2.3 result, particularly since our somewhat higher metallicities (by around 0.1 dex) are qualitatively consistent with the lower mean redshift (z = 1.76) of our sample. For the masses probed by our data, the MZ relation shows a steep slope which is suggestive of feedback from energy-driven winds, and a cosmological downsizing evolution where high mass galaxies reach the local MZ relation at earlier times. In addition, we show that our sample falls on an extrapolation of the star-forming main sequence (the SFR-M_* relation) at this redshift. This result indicates that grism emission-line selected samples do not have preferentially high star formation rates (SFRs). Finally, we report no evidence for evolution of the mass-metallicity-SFR plane; our stack-averaged measurements show excellent agreement with the local relation

Concurrent Oral 1 - Therapy of rheumatic disease: OP4. Effectiveness of Rituximab in Rheumatoid Arthritis: Results from the British Society for Rheumatology Biologics Register (BSRBR)

Background: Rituximab (RTX) in combination with methotrexate (MTX) has been licensed since 2006 for the management of severe active rheumatoid arthritis (RA) in patients who have failed at least one anti-tumour necrosis factor (anti-TNF) therapy. Published clinical trials have demonstrated the efficacy of RTX in improving both clinical symptoms and patients' physical function. This study aimed to assess the effectiveness of RTX in RA patients treated in routine clinical practice by examining clinical and patient reported outcomes six months after receiving a first course of RTX. Methods: The analysis involved 550 RA patients registered with the BSRBR, who were starting RTX and were followed up for at least 6 months. Change in Disease Activity Score (DAS28) and European League Against Rheumatism (EULAR) response were used to assess the clinical response while change in Health Assessment Questionnaire (HAQ) score was used to assess the physical function of the patients 6 months after starting RTX. The change in DAS28 and HAQ was compared between seronegative and seropositive patients and anti-TNF naïve patients versus anti-TNF failures. The response was also compared between patients receiving RTX in combination with MTX, other non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) or no nbDMARDs. Results: The mean (s.d.) age of the cohort was 59 (12) years and 78% of the patients were females. The patients had a mean (s.d.) of 15 (10) years of disease duration. 16% were biologic naïve while 84% were anti-TNF failures. 32% of the patients were seronegative and 68% were seropositive. The mean (95% CI) DAS28 at baseline was 6.2 (6.1, 6.3) which decreased to 4.8 (4.7, 4.9) at 6 months of follow up. 16% were EULAR good responders, 43% were moderate responders and 41% were non responders. The mean (95% CI) change in HAQ was −0.1 (−0.2, −0.1) (Table 1). The mean change in DAS28 was similar in seropositive and seronegative patients (p = 0.18) while the anti-TNF naïve patients showed a greater reduction in DAS28 scores than anti-TNF failures (p = 0.05). Patients receiving RTX in combination with MTX showed similar changes in DAS28 and HAQ compared to patients receiving RTX alone or with other nbDMARDs. Conclusions: RTX has proven to be effective in the routine clinical practice. Anti-TNF naïve patients seem to benefit more from RTX treatment than anti-TNF failures. Disclosure statement: The authors have declared no conflicts of interes

Analysis of the African coelacanth genome sheds light on tetrapod evolution

It was a zoological sensation when a living specimen of the coelacanth was first discovered in 1938, as this lineage of lobe-finned fish was thought to have gone extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features . Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain, and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues demonstrate the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes