IRC+10216's Innermost Envelope -- The eSMA's View

We used the Extended Submillimeter Array (eSMA) in its most extended configuration to investigate the innermost (within a radius of 290 R* from the star) circumstellar envelope (CSE) of IRC+10216. We imaged the CSE using HCN and other molecular lines with a beam size of 0."22 x 0."46, deeply into the very inner edge (15 R*) of the envelope where the expansion velocity is only 3 km/s. The excitation mechanism of hot HCN and KCl maser lines is discussed. HCN maser components are spatially resolved for the first time on an astronomical object. We identified two discrete regions in the envelope: a region with a radius of . 15 R*, where molecular species have just formed and the gas has begun to be accelerated (region I) and a shell region (region II) with a radius of 23 R* and a thickness of 15 R*, whose expansion velocity has reached up to 13 km/s, nearly the terminal velocity of 15 km/s. The Si$^{34}$S line detected in region I shows a large expansion velocity of 16 km/s due to strong wing components, indicating that the emission may arise from a shock region in the innermost envelope. In region II, the P.A. of the most copious mass loss direction was found to be 120 +/- 10 degrees, which may correspond to the equatorial direction of the star. Region II contains a torus-like feature. These two regions may have emerged due to significant differences in the size distributions of the dust particles in the two regions.Comment: 26 pages, 8 figures, accepted for publication in The Astrophysical Journal. Please find the pdf at http://www.submm.caltech.edu/~hs/astroph/0904.0280.pdf and the ps file at http://www.submm.caltech.edu/~hs/astroph/0904.0280.p

Bacterial Adaptation to the Host's Diet Is a Key Evolutionary Force Shaping Drosophila-Lactobacillus Symbiosis

Animal-microbe facultative symbioses play a fundamental role in ecosystem and organismal health. Yet, due to the flexible nature of their association, the selection pressures that act on animals and their facultative symbionts remain elusive. Here we apply experimental evolution to Drosophila melanogaster associated with its growth-promoting symbiont Lactobacillus plantarum, representing a well-established model of facultative symbiosis. We find that the diet of the host, rather than the host itself, is a predominant driving force in the evolution of this symbiosis. Furthermore, we identify a mechanism resulting from the bacterium's adaptation to the diet, which confers growth benefits to the colonized host. Our study reveals that bacterial adaptation to the host's diet may be the foremost step in determining the evolutionary course of a facultative animal-microbe symbiosis

The eSMA: description and first results

The eSMA ("extended SMA") combines the SMA, JCMT and CSO into a single facility, providing enhanced sensitivity and spatial resolution owing to the increased collecting area at the longest baselines. Until ALMA early science observing (2011), the eSMA will be the facility capable of the highest angular resolution observations at 345 GHz. The gain in sensitivity and resolution will bring new insights in a variety of fields, such as protoplanetary/transition disks, high-mass star formation, solar system bodies, nearby and high-z galaxies. Therefore the eSMA is an important facility to prepare the grounds for ALMA and train scientists in the techniques. Over the last two years, and especially since November 2006, there has been substantial progress toward making the eSMA into a working interferometer. In particular, (i) new 345-GHz receivers, that match the capabilities of the SMA system, were installed at the JCMT and CSO; (ii) numerous tests have been performed for receiver, correlator and baseline calibrations in order to determine and take into account the effects arising from the differences between the three types of antennas; (iii) first fringes at 345 GHz were obtained on August 30 2007, and the array has entered the science-verification stage. We report on the characteristics of the eSMA and its measured performance at 230 GHz and that expected at 345 GHz. We also present the results of the commissioning and some initial science-verification observations, including the first absorption measurement of the C/CO ratio in a galaxy at z=0.89, located along the line of sight to the lensed quasar PKS1830-211, and on the imaging of the vibrationally excited HCN line towards IRC+10216.Comment: 12 pages, 7 figures, paper number 7012-12, to appear in Proceedings of SPIE vol. 7012: "Ground-based and Airborne Telescopes II", SPIE conference on Astronomical Instrumentation, Marseille, 23-28 June 200

Detection of CI in absorption towards PKS 1830-211 with the eSMA

We report the first science observations and results obtained with the "extended" SMA (eSMA), which is composed of the SMA (Submillimeter Array), JCMT (James Clerk Maxwell Telescope) and CSO (Caltech Submillimeter Observatory). Redshifted absorptions at z=0.886 of CI (^3P_1 - ^3P_0) were observed with the eSMA with an angular resolution of 0.55"x0.22" at 1.1 mm toward the southwestern image of the remarkable lensed quasar PKS 1830-211, but not toward the northeastern component at a separation of ~1". Additionally, SMA observations of CO, 13CO and C18O (all J=4-3) were obtained toward this object: CO was also detected toward the SW component, but none of the isotopologues were. This is the first time [CI] is detected in this object, allowing the first direct determination of relative abundances of neutral atomic carbon to CO in the molecular clouds of a spiral galaxy at z>0.1. The [CI] and CO profiles can be decomposed into two and three velocity components respectively. We derive C/CO column density ratios ranging from <0.5 (representative of dense cores) to ~2.5 (close to translucent clouds values). This could indicate that we are seeing environments with different physical conditions or that we are witnessing chemical evolution of regions where C has not completely been converted into CO.Comment: 6 pages using emulateapj, 3 tables, 2 figures ; accepted for publication in ApJ

Evidence of coat color variation sheds new light on ancient canids.

International audienceWe have used a paleogenetics approach to investigate the genetic landscape of coat color variation in ancient Eurasian dog and wolf populations. We amplified DNA fragments of two genes controlling coat color, Mc1r (Melanocortin 1 Receptor) and CBD103 (canine-β-defensin), in respectively 15 and 19 ancient canids (dogs and wolf morphotypes) from 14 different archeological sites, throughout Asia and Europe spanning from ca. 12 000 B.P. (end of Upper Palaeolithic) to ca. 4000 B.P. (Bronze Age). We provide evidence of a new variant (R301C) of the Melanocortin 1 receptor (Mc1r) and highlight the presence of the beta-defensin melanistic mutation (CDB103-K locus) on ancient DNA from dog-and wolf-morphotype specimens. We show that the dominant K(B) allele (CBD103), which causes melanism, and R301C (Mc1r), the variant that may cause light hair color, are present as early as the beginning of the Holocene, over 10 000 years ago. These results underline the genetic diversity of prehistoric dogs. This diversity may have partly stemmed not only from the wolf gene pool captured by domestication but also from mutations very likely linked to the relaxation of natural selection pressure occurring in-line with this process

Cost-effectiveness analysis of adalimumab for the treatment of uveitis associated with Juvenile Idiopathic Arthritis

Purpose To investigate the cost effectiveness of adalimumab in combination with methotrexate, compared with methotrexate alone, for the management of uveitis associated with juvenile idiopathic arthritis (JIA). Design A cost-utility analysis based on a clinical trial and decision analytic model. Participants Children and adolescents 2 to 18 years of age with persistently active uveitis associated with JIA, despite optimized methotrexate treatment for at least 12 weeks. Methods The SYCAMORE (Randomised controlled trial of the clinical effectiveness, SafetY and Cost effectiveness of Adalimumab in combination with MethOtRExate for the treatment of juvenile idiopathic arthritis associated uveitis) trial (identifier, ISRCTN10065623) of methotrexate (up to 25 mg weekly) with or without fortnightly administered adalimumab (20 or 40 mg, according to body weight) provided data on resource use (based on patient self-report and electronic records) and health utilities (from the Health Utilities Index questionnaire). Surgical event rates and long-term outcomes were based on data from a 10-year longitudinal cohort. A Markov model was used to extrapolate the effects of treatment based on visual impairment. Main Outcome Measures Medical costs to the National Health Service in the United Kingdom, utility of defined health states, quality-adjusted life-years (QALYs), and incremental cost per QALY. Results Adalimumab in combination with methotrexate resulted in additional costs of £39 316, with a 0.30 QALY gain compared with methotrexate alone, resulting in an incremental cost-effectiveness ratio of £129 025 per QALY gained. The probability of cost effectiveness at a threshold of £30 000 per QALY was less than 1%. Based on a threshold analysis, a price reduction of 84% would be necessary for adalimumab to be cost effective. Conclusions Adalimumab is clinically effective in uveitis associated with JIA; however, its cost effectiveness is not demonstrated compared with methotrexate alone in the United Kingdom setting

Adalimumab in combination with methotrexate for refractory uveitis associated with juvenile idiopathic arthritis: a RCT

Abstract Background Children with juvenile idiopathic arthritis (JIA) are at risk of uveitis. The role of adalimumab (Humira®; AbbVie Inc., Ludwigshafen, Germany) in the management of uveitis in children needs to be determined. Objective To compare the efficacy, safety and cost-effectiveness of adalimumab in combination with methotrexate (MTX) versus placebo with MTX alone, with regard to controlling disease activity in refractory uveitis associated with JIA. Design This was a randomised (applying a ratio of 2 : 1 in favour of adalimumab), double-blind, placebo-controlled, multicentre parallel-group trial with an integrated economic evaluation. A central web-based system used computer-generated tables to allocate treatments. A cost–utility analysis based on visual acuity was conducted and a 10-year extrapolation by Markov modelling was also carried out. Setting The setting was tertiary care centres throughout the UK. Participants Patients aged 2–18 years inclusive, with persistently active JIA-associated uveitis (despite optimised MTX treatment for at least 12 weeks). Interventions All participants received a stable dose of MTX and either adalimumab (20 mg/0.8 ml for patients weighing < 30 kg or 40 mg/0.8 ml for patients weighing ≥ 30 kg by subcutaneous injection every 2 weeks based on body weight) or a placebo (0.8 ml as appropriate according to body weight by subcutaneous injection every 2 weeks) for up to 18 months. A follow-up appointment was arranged at 6 months. Main outcome measures Primary outcome – time to treatment failure [multicomponent score as defined by set criteria based on the Standardisation of Uveitis Nomenclature (SUN) criteria]. Economic outcome – incremental cost per quality-adjusted life-year (QALY) gained from the perspective of the NHS in England and Personal Social Services providers. Full details of secondary outcomes are provided in the study protocol. Results A total of 90 participants were randomised (adalimumab, n = 60; placebo, n = 30). There were 14 (23%) treatment failures in the adalimumab group and 17 (57%) in the placebo group. The analysis of the data from the double-blind phase of the trial showed that the hazard risk (HR) of treatment failure was significantly reduced, by 75%, for participants in the adalimumab group (HR 0.25, 95% confidence interval 0.12 to 0.51; p < 0.0001 from log-rank test). The cost-effectiveness of adalimumab plus MTX was £129,025 per QALY gained. Adalimumab-treated participants had a much higher incidence of adverse and serious adverse events. Conclusions Adalimumab in combination with MTX is safe and effective in the management of JIA-associated uveitis. However, the likelihood of cost-effectiveness is < 1% at the £30,000-per-QALY threshold. Future work A clinical trial is required to define the most effective time to stop therapy. Prognostic biomarkers of early and complete response should also be identified

Associations between childhood maltreatment and inflammatory markers.

BACKGROUND:Childhood maltreatment is one of the strongest predictors of adulthood depression and alterations to circulating levels of inflammatory markers is one putative mechanism mediating risk or resilience.AimsTo determine the effects of childhood maltreatment on circulating levels of 41 inflammatory markers in healthy individuals and those with a major depressive disorder (MDD) diagnosis. METHOD:We investigated the association of childhood maltreatment with levels of 41 inflammatory markers in two groups, 164 patients with MDD and 301 controls, using multiplex electrochemiluminescence methods applied to blood serum. RESULTS:Childhood maltreatment was not associated with altered inflammatory markers in either group after multiple testing correction. Body mass index (BMI) exerted strong effects on interleukin-6 and C-reactive protein levels in those with MDD. CONCLUSIONS:Childhood maltreatment did not exert effects on inflammatory marker levels in either the participants with MDD or the control group in our study. Our results instead highlight the more pertinent influence of BMI.Declaration of interestD.A.C. and H.W. work for Eli Lilly Inc. R.N. has received speaker fees from Sunovion, Jansen and Lundbeck. G.B. has received consultancy fees and funding from Eli Lilly. R.H.M.-W. has received consultancy fees or has a financial relationship with AstraZeneca, Bristol-Myers Squibb, Cyberonics, Eli Lilly, Ferrer, Janssen-Cilag, Lundbeck, MyTomorrows, Otsuka, Pfizer, Pulse, Roche, Servier, SPIMACO and Sunovian. I.M.A. has received consultancy fees or has a financial relationship with Alkermes, Lundbeck, Lundbeck/Otsuka, and Servier. S.W. has sat on an advisory board for Sunovion, Allergan and has received speaker fees from Astra Zeneca. A.H.Y. has received honoraria for speaking from Astra Zeneca, Lundbeck, Eli Lilly, Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion, Janssen; and research grant support from Janssen. A.J.C. has received honoraria for speaking from Astra Zeneca, honoraria for consulting with Allergan, Livanova and Lundbeck and research grant support from Lundbeck

Subinhibitory Arsenite Concentrations Lead to Population Dispersal in Thiomonas sp.

Biofilms represent the most common microbial lifestyle, allowing the survival of microbial populations exposed to harsh environmental conditions. Here, we show that the biofilm development of a bacterial species belonging to the Thiomonas genus, frequently found in arsenic polluted sites and playing a key role in arsenic natural remediation, is markedly modified when exposed to subinhibitory doses of this toxic element. Indeed, arsenite [As(III)] exposure led to a considerable impact on biofilm maturation by strongly increasing the extracellular matrix synthesis and by promoting significant cell death and lysis within microcolonies. These events were followed by the development of complex 3D-biofilm structures and subsequently by the dispersal of remobilized cells observed inside the previously formed hollow voids. Our results demonstrate that this biofilm community responds to arsenite stress in a multimodal way, enhancing both survival and dispersal. Addressing this complex bacterial response to As(III) stress, which might be used by other microorganisms under various adverse conditions, may be essential to understand how Thiomonas strains persist in extreme environments