Functional interaction between Sequestosome-1/p62 and Autophagy-Linked FYVE-containing protein WDFY3 in human osteoclasts

Peer reviewedPostprin

The Coevality of Young Binary Systems

Multiple star systems are commonly assumed to form coevally; they thus provide the anchor for most calibrations of stellar evolutionary models. In this paper we study the binary population of the Taurus-Auriga association, using the component positions in an HR diagram in order to quantify the frequency and degree of coevality in young binary systems. After identifying and rejecting the systems that are known to be affected by systematic errors (due to further multiplicity or obscuration by circumstellar material), we find that the relative binary ages, |Delta log(tau)|, have an overall dispersion of sigma~0.40 dex. Random pairs of Taurus members are coeval only to within sigma~0.58 dex, indicating that Taurus binaries are indeed more coeval than the association as a whole. However, the distribution of |Delta log(tau)| suggests two populations, with ~2/3 of the sample appearing coeval to within the errors (sigma~0.16 dex) and the other ~1/3 distributed in an extended tail reaching |Delta log(tau)|~0.4-0.9 dex. To explain the finding of a multi-peaked distribution, we suggest that the tail of the differential age distribution includes unrecognized hierarchical multiples, stars seen in scattered light, or stars with disk contamination; additional followup is required to rule out or correct for these explanations. The relative coevality of binary systems does not depend significantly on the system mass, mass ratio, or separation. Indeed, any pair of Taurus members wider than ~10' (~0.7 pc) shows the full age spread of the association.Comment: 23 pages, 11 figures; accepted to Ap

Low-Dose Intravenous Immunoglobulin Treatment for Long-Standing Complex Regional Pain Syndrome: A Randomized Trial

Background: Two small trials suggest that low-dose intravenous immunoglobulin (IVIg) may improve the symptoms of complex regional pain syndrome (CRPS), a rare posttraumatic pain condition. Objective: To confirm the efficacy of low-dose IVIg compared with placebo in reducing pain during a 6-week period in adult patients who had CRPS from 1 to 5 years. Design: 1:1 parallel, randomized, placebo-controlled, multicenter trial for 6 weeks, with an optional 6-week open extension. Patients were randomly assigned to 1 of 2 study groups between 27 August 2013 and 28 October 2015; the last patient completed follow-up on 21 March 2016. Patients, providers, researchers, and outcome assessors were blinded to treatment assignment. (ISRCTN42179756) Setting: 7 secondary and tertiary care pain management centers in the United Kingdom. Participants: 111 patients with moderate or severe CRPS of 1 to 5 years' duration. Intervention: IVIg, 0.5 g/kg of body weight, or visually indistinguishable placebo of 0.1% albumin in saline on days 1 and 22 after randomization. Measurements: The primary outcome was 24-hour average pain intensity, measured daily between days 6 and 42, on an 11-point (0- to 10-point) rating scale. Secondary outcomes were pain interference and quality of life. Results: The primary analysis sample consisted of 108 eligible patients, 103 of whom had outcome data. Mean (average) pain scores were 6.9 points (SD, 1.5) for placebo and 7.2 points (SD, 1.3) for IVIg. The adjusted difference in means was 0.27 (95% CI, −0.25 to 0.80; P = 0.30), which excluded the prespecified, clinically important difference of −1.2. No statistically significant differences in secondary outcomes were found between the groups. In the open extension, 12 of the 67 patients (18%) who received 2 IVIg infusions had pain reduction of at least 2 points compared with their baseline score. Two patients in the blinded phase (1 in the placebo and 1 in the IVIg group) and 4 in the open IVIg phase had serious events. Limitations: Results do not apply to patients who have had CRPS for less than 1 year or more than 5 years and do not extend to full-dose treatment (for example, 2 g/kg). The study was inadequately powered to detect subgroup effects. Conclusion: Low-dose immunoglobulin treatment for 6 weeks was not effective in relieving pain in patients with moderate to severe CRPS of 1 to 5 years' duration

Levothyroxine in Women with Thyroid Peroxidase Antibodies before Conception

BackgroundThyroid peroxidase antibodies are associated with an increased risk of miscarriage and preterm birth, even when thyroid function is normal. Small trials indicate that the use of levothyroxine could reduce the incidence of such adverse outcomes.MethodsWe conducted a double-blind, placebo-controlled trial to investigate whether levothyroxine treatment would increase live-birth rates among euthyroid women who had thyroid peroxidase antibodies and a history of miscarriage or infertility. A total of 19,585 women from 49 hospitals in the United Kingdom underwent testing for thyroid peroxidase antibodies and thyroid function. We randomly assigned 952 women to receive either 50 μg once daily of levothyroxine (476 women) or placebo (476 women) before conception through the end of pregnancy. The primary outcome was live birth after at least 34 weeks of gestation.ResultsThe follow-up rate for the primary outcome was 98.7% (940 of 952 women). A total of 266 of 470 women in the levothyroxine group (56.6%) and 274 of 470 women in the placebo group (58.3%) became pregnant. The live-birth rate was 37.4% (176 of 470 women) in the levothyroxine group and 37.9% (178 of 470 women) in the placebo group (relative risk, 0.97; 95% confidence interval [CI], 0.83 to 1.14, P=0.74; absolute difference, −0.4 percentage points; 95% CI, −6.6 to 5.8). There were no significant between-group differences in other pregnancy outcomes, including pregnancy loss or preterm birth, or in neonatal outcomes. Serious adverse events occurred in 5.9% of women in the levothyroxine group and 3.8% in the placebo group (P=0.14).ConclusionsThe use of levothyroxine in euthyroid women with thyroid peroxidase antibodies did not result in a higher rate of live births than placebo. (Funded by the United Kingdom National Institute for Health Research; TABLET Current Controlled Trials number, ISRCTN15948785.

Standards of care for obsessive–compulsive disorder centres

In recent years, many assessment and care units for obsessive–compulsive disorder (OCD) have been set up in order to detect, diagnose and to properly manage this complex disorder, but there is no consensus regarding the key functions that these units should perform. The International College of Obsessive- Compulsive Spectrum Disorders (ICOCS) together with the Obsessive Compulsive and Related Disorders Network (OCRN) of the European College of Neuropsychopharmacology (ECNP) and the Anxiety and Obsessive Compulsive Disorders Section of the World Psychiaric Association (WPA) has developed a stand- ards of care programme for OCD centres. The goals of this collaborative initiative are promoting basic standards, improving the quality of clinical care and enhance the validity and reliability of research results provided by different facilities and countries

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Abstracts from the NIHR INVOLVE Conference 2017

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