The risk and nature of flares in juvenile idiopathic arthritis: Results from the ReACCh-Out cohort

Objective To describe probabilities and characteristics of disease flares in children with juvenile idiopathic arthritis ( JIA) and to identify clinical features associated with an increased risk of flare. Methods We studied children in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) prospective inception cohort. A flare was defined as a recurrence of disease manifestations after attaining inactive disease and was called significant if it required intensification of treatment. Probability of first flare was calculated with Kaplan-Meier methods, and associated features were identified using Cox regression. Results 1146 children were followed up a median of 24 months after attaining inactive disease. We observed 627 first flares (54.7% of patients) with median active joint count of 1, physician global assessment (PGA) of 12 mm and duration of 27 weeks. Within a year after attaining inactive disease, the probability of flare was 42.5% (95% CI 39% to 46%) for any flare and 26.6% (24% to 30%) for a significant flare. Within a year after stopping treatment, it was 31.7% (28% to 36%) and 25.0% (21% to 29%), respectively. A maximum PGA \u3e30 mm, maximum active joint count \u3e4, rheumatoid factor (RF)-positive polyarthritis, antinuclear antibodies (ANA) and receiving disease-modifying antirheumatic drugs (DMARDs) or biological agents before attaining inactive disease were associated with increased risk of flare. Systemic JIA was associated with the lowest risk of flare. Conclusions In this real-practice JIA cohort, flares were frequent, usually involved a few swollen joints for an average of 6 months and 60% led to treatment intensification. Children with a severe disease course had an increased risk of flare

TOI-2015b: A Warm Neptune with Transit Timing Variations Orbiting an Active mid M Dwarf

We report the discovery of a close-in ($P_{\mathrm{orb}} = 3.349\:\mathrm{days}$) warm Neptune with clear transit timing variations (TTVs) orbiting the nearby ($d=47.3\:\mathrm{pc}$) active M4 star, TOI-2015. We characterize the planet's properties using TESS photometry, precise near-infrared radial velocities (RV) with the Habitable-zone Planet Finder (HP) Spectrograph, ground-based photometry, and high-contrast imaging. A joint photometry and RV fit yields a radius $R_p~=~3.37_{-0.20}^{+0.15} \:\mathrm{R_\oplus}$, mass $m_p~=~16.4_{-4.1}^{+4.1}\:\mathrm{M_\oplus}$, and density $\rho_p~=~2.32_{-0.37}^{+0.38} \:\mathrm{g cm^{-3}}$ for TOI-2015b, suggesting a likely volatile-rich planet. The young, active host star has a rotation period of $P_{\mathrm{rot}}~=~8.7 \pm~0.9~\mathrm{days}$ and associated rotation-based age estimate of $1.1~\pm~0.1\:\mathrm{Gyr}$. Though no other transiting planets are seen in the TESS data, the system shows clear TTVs of super period $P_{\mathrm{sup}}~\approx~430\:\mathrm{days}$ and amplitude $\sim$$100\:\mathrm{minutes}$. After considering multiple likely period ratio models, we show an outer planet candidate near a 2:1 resonance can explain the observed TTVs while offering a dynamically stable solution. However, other possible two-planet solutions -- including 3:2 and 4:3 resonance -- cannot be conclusively excluded without further observations. Assuming a 2:1 resonance in the joint TTV-RV modeling suggests a mass of $m_b~=~13.3_{-4.5}^{+4.7}\:\mathrm{M_\oplus}$ for TOI-2015b and $m_c~=~6.8_{-2.3}^{+3.5}\:\mathrm{M_\oplus}$ for the outer candidate. Additional transit and RV observations will be beneficial to explicitly identify the resonance and further characterize the properties of the system.Comment: 28 pages, 15 figures, 6 tables. As submitted to AAS Journal

L Dwarfs Found in Sloan Digital Sky Survey Commissioning Data II. Hobby-Eberly Telescope Observations

Low dispersion optical spectra have been obtained with the Hobby-Eberly Telescope of 22 very red objects found in early imaging data from the Sloan Digital Sky Survey. The objects are assigned spectral types on the 2MASS system (Kirkpatrick et al. 1999) and are found to range from late M to late L. The red- and near-infrared colors from SDSS and 2MASS correlate closely with each other, and most of the colors are closely related to spectral type in this range; the exception is the (i^* - z^*) color, which appears to be independent of spectral type between about M7 and L4. The spectra suggest that this independence is due to the disappearance of the TiO and VO absorption in the i-band for later spectral types; to the presence of strong Na I and K I absorption in the i-band; and to the gradual disappearance of the 8400 Angstrom absorption of TiO and FeH in the z-band.Comment: 20 pages, 7 figures, accepted by AJ, a version with higher resolution figures can be found at ftp://ftp.astro.psu.edu/pub/dps/hetld.p

Toward Large-Area Sub-Arcsecond X-Ray Telescopes II

In order to advance significantly scientific objectives, future x-ray astronomy missions will likely call for x-ray telescopes with large aperture areas (approx. = 3 sq m) and fine angular resolution (approx. = 1"). Achieving such performance is programmatically and technologically challenging due to the mass and envelope constraints of space-borne telescopes and to the need for densely nested grazing-incidence optics. Such an x-ray telescope will require precision fabrication, alignment, mounting, and assembly of large areas (approx. = 600 sq m) of lightweight (approx. = 2 kg/sq m areal density) high-quality mirrors, at an acceptable cost (approx. = 1 M$/sq m of mirror surface area). This paper reviews relevant programmatic and technological issues, as well as possible approaches for addressing these issues-including direct fabrication of monocrystalline silicon mirrors, active (in-space adjustable) figure correction of replicated mirrors, static post-fabrication correction using ion implantation, differential erosion or deposition, and coating-stress manipulation of thin substrates

Burn injury leads to increased long-term susceptibility to respiratory infection in both mouse models and population studies

Background: Burn injury initiates an acute inflammatory response that subsequently drives wound repair. However, acute disruption to the immune response is also common, leading to susceptibility to sepsis and increased morbidity and mortality. Despite increased understanding of the impact of burn injury on the immune system in the acute phase, little is known about longterm consequences of burn injury on immune function. This study was established to determine whether burn injury has long-term clinical impacts on patients' immune responses. Methods: Using a population-based retrospective longitudinal study and linked hospital morbidity and death data from Western Australia, comparative rates of hospitalisation for respiratory infections in burn patients and a non-injured comparator cohort were assessed. In addition, a mouse model of non-severe burn injury was also used in which viral respiratory infection was induced at 4 weeks post-injury using a mouse modified version of the Influenza A virus (H3NN; A/mem/71-a). Results and conclusions: The burn injured cohort contained 14893 adult patients from 1980-2012 after removal of those patients with evidence of smoke inhalation or injury to the respiratory tract. During the study follow-up study a total of 2,884 and 2,625 respiratory infection hospital admissions for the burn and uninjured cohorts, respectively, were identified. After adjusting for covariates, the burn cohort experienced significantly elevated admission rates for influenza and viral pneumonia (IRR, 95%CI: 1.73, 1.27-2.36), bacterial pneumonia (IRR, 95%CI: 2.05, 1.85-2.27) and for other types of upper and lower respiratory infections (IRR, 95% CI: 2.38, 2.09-2.71). In the mouse study an increased viral titre was observed after burn injury, accompanied by a reduced CD8 response and increased NK and NKT cells in the draining lymph nodes. This data suggests burn patients are at long-term increased risk of infection due to sustained modulation of the immune response

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations