X-ray and Near-IR Variability of the Anomalous X-ray Pulsar 1E 1048.1-5937: From Quiescence Back to Activity

(Abridged) We report on new and archival X-ray and near-infrared observations of the anomalous X-ray pulsar 1E 1048.1-5937 performed between 2001-2007 with RXTE, CXO, Swift, HST, and VLT. During its ~2001-2004 active period, 1E 1048.-5937 exhibited two large, long-term X-ray pulsed-flux flares as well as short bursts, and large (>10x) torque changes. Monitoring with RXTE revealed that the source entered a phase of timing stability in 2004; at the same time, a series of four simultaneous observations with CXO and HST in 2006 showed that its X-ray flux and spectrum and near-IR flux, all variable prior to 2005, stabilized. The near-IR flux, when detected by HST (H~22.7 mag) and VLT (K_S~21.0 mag), was considerably fainter than previously measured. Recently, in 2007 March, this newfound quiescence was interrupted by a sudden flux enhancement, X-ray spectral changes and a pulse morphology change, simultaneous with a large spin-up glitch and near-IR enhancement. Our RXTE observations revealed a sudden pulsed flux increase by a factor of ~3 in the 2-10 keV band. In observations with CXO and Swift, we found that the total X-ray flux increased much more than the pulsed flux, reaching a peak value of >7 times the quiescent value (2-10 keV). With these recent data, we find a strong anti-correlation between X-ray flux and pulsed fraction, and a correlation between X-ray spectral hardness and flux. Simultaneously with the radiative and timing changes, we observed a significant X-ray pulse morphology change such that the profile went from nearly sinusoidal to having multiple peaks. We compare these remarkable events with other AXP outbursts and discuss implications in the context of the magnetar model and other models of AXP emission.Comment: 13 pages (6 figures) in emulateapj style. Accepted for publication in ApJ. New version includes referee's corrections; split Figure 1 into 2 figures; modified Figs. 4b and 6b; rearranged and renumbered of some figures and sections; added an X-ray dataset; improved analysis of pulse morphology and pulsed fraction; added paragraph to sec. 3.2.

Correlated Infrared and X-ray Flux Changes Following the 2002 June Outburst of the Anomalous X-ray Pulsar 1E 2259+586

We present the results of a near-infrared monitoring program of the Anomalous X-ray Pulsar 1E 2259+586, performed at the Gemini Observatory. This program began three days after the pulsar's 2002 June outburst, and spans ~1.5 years. We find that after an initial increase associated with the outburst, the near-infrared flux decreased continually and reached the pre-burst quiescent level after about one year. We compare both the near-infrared flux enhancement and its decay to those of the X-ray afterglow, and find them to be remarkably consistent. Fitting simple power laws to the RXTE pulsed flux and near-infrared data for t>1 day post-burst, we find the following decay indices: alpha=-0.21+/-0.01 (X-ray), alpha=-0.21+/-0.02 (near-infrared), where flux is a function of time such that F is proportional to t^alpha. This suggests that the enhanced infrared and X-ray fluxes have a physical link post-outburst, most likely from the neutron-star magnetosphere.Comment: 11 pages, 1 figure, accepted for publication in ApJL; minor wording changes, added observation program IDs, improved figure resolutio

Chandra Monitoring of the Candidate Anomalous X-ray Pulsar AX J1845.0-0258

The population of clearly identified anomalous X-ray pulsars has recently grown to seven, however, one candidate anomalous X-ray pulsar (AXP) still eludes re-confirmation. Here, we present a set of seven Chandra ACIS-S observations of the transient pulsar AX J1845.0-0258, obtained during 2003. Our observations reveal a faint X-ray point source within the ASCA error circle of AX J1845.0-0258's discovery, which we designate CXOU J184454.6-025653 and tentatively identify as the quiescent AXP. Its spectrum is well described by an absorbed single-component blackbody (kT~2.0 keV) or power law (Gamma~1.0) that is steady in flux on timescales of at least months, but fainter than AX J1845.0-0258 was during its 1993 period of X-ray enhancement by at least a factor of 13. Compared to the outburst spectrum of AX J1845.0-0258, CXOU J184454.6-025653 is considerably harder: if truly the counterpart, then its spectral behaviour is contrary to that seen in the established transient AXP XTE J1810-197, which softened from kT~0.67 keV to ~0.18 keV in quiescence. This unexpected result prompts us to examine the possibility that we have observed an unrelated source, and we discuss the implications for AXPs, and magnetars in general.Comment: 4 pages, 3 figures. To be published in the proceedings of the conference "Isolated Neutron Stars: from the Interior to the Surface" (April 24-28, 2006, London, UK), eds. D. Page, R. Turolla, & S. Zan

A multicomponent intervention for the management of chronic pain in older adults: study protocol for a randomized controlled trial

Background: Studies have shown that physical interventions and psychological methods based on the cognitive behavioral approach are efficacious in alleviating pain and that combining both tends to yield more benefits than either intervention alone. In view of the aging population with chronic pain and the lack of evidence-based pain management programs locally, we developed a multicomponent intervention incorporating physical exercise and cognitive behavioral techniques and examined its long-term effects against treatment as usual (i.e., pain education) in older adults with chronic musculoskeletal pain in Hong Kong. Methods/design: We are conducting a double-blind, cluster-randomized controlled trial. A sample of 160 participants aged ≥ 60 years will be recruited from social centers or outpatient clinics and will be randomized on the basis of center/clinic to either the multicomponent intervention or the pain education program. Both interventions consist of ten weekly sessions of 90 minutes each. The primary outcome is pain intensity, and the secondary outcomes include pain interference, pain persistence, pain self-efficacy, pain coping, pain catastrophizing cognitions, health-related quality of life, depressive symptoms, and hip and knee muscle strength. All outcome measures will be collected at baseline, postintervention, and at 3 and 6 months follow-up. Intention-to-treat analysis will be performed using mixed-effects regression to see whether the multicomponent intervention alleviates pain intensity and associated outcomes over and above the effects of pain education (i.e., a treatment × time intervention effect). Discussion: Because the activities included in the multicomponent intervention were carefully selected for ready implementation by allied health professionals in general, the results of this study, if positive, will make available an efficacious, nonpharmacological pain management program that can be widely adopted in clinical and social service settings and will hence improve older people’s access to pain management services

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

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

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely