Anti-CTLA-4 (CD 152) monoclonal antibody-induced autoimmune interstitial nephritis

Targeted immune-modulating agents are entering clinical practice in many specialties, providing novel therapeutic possibilities but introducing new potential toxicities. We present the first reported case, to our knowledge, of immune-mediated nephritis following the administration of Tremelimumab (CP-675, 206), an anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibody. High-dose steroid therapy led to a rapid improvement in renal function, avoiding the need for renal replacement therapy.Peer reviewe

Separated Fringe Packet Observations with the CHARA Array III. The Very High Eccentricity Binary HR 7345

After an eleven year observing campaign, we present the combined visual{spectroscopic orbit of the formerly unremarkable bright star HR 7345 (HD 181655, HIP 94981, GJ 754.2). Using the Separated Fringe Packet (SFP) method with the CHARA Array, we were able to determine a difficult to complete orbital period of 331.609 +/- 0.004 days. The 11 month period causes the system to be hidden from interferometric view behind the Sun for 3 years at a time. Due to the high eccentricity orbit of about 90% of a year, after 2018 January the periastron phase will not be observable again until late 2021. Hindered by its extremely high eccentricity of 0.9322 +/- 0.0001, the double-lined spectroscopic phase of HR 7345 is observable for 15 days. Such a high eccentricity for HR 7345 places it among the most eccentric systems in catalogs of both visual and spectroscopic orbits. For this system we determine nearly identical component masses of 0.941 +/- 0.076 Msun and 0.926 +/- 0.075 Msun as well as an orbital parallax of 41.08 +/- 0.77 mas.Comment: 20 pages, 3 figures, 4 table

An interferometric study of the post-AGB binary 89 Herculis I Spatially resolving the continuum circumstellar environment at optical and near-IR wavelengths with the VLTI, NPOI, IOTA, PTI, and the CHARA Array

Binary post-AGB stars are interesting laboratories to study both the evolution of binaries as well as the structure of circumstellar disks. A multiwavelength high angular resolution study of the prototypical object 89 Herculis is performed with the aim of identifying and locating the different emission components seen in the SED. A large interferometric data set, collected over the past decade and covering optical and near-IR wavelengths, is analyzed with simple geometric models. Combining the interferometric constraints with the photometry and the optical spectra, we reassess the energy budget of the post-AGB star and its circumstellar environment. We report the first (direct) detection of a large (35-40%) optical circumstellar flux contribution and spatially resolve its emission region. Given this large amount of reprocessed and/or redistributed optical light, the fitted size of the emission region is rather compact and fits with(in) the inner rim of the circumbinary dust disk. This rim dominates our K band data through thermal emission and is rather compact, emitting significantly already at a radius of twice the orbital separation. We interpret the circumstellar optical flux as due to a scattering process, with the scatterers located in the extremely puffed-up inner rim of the disk and possibly also in a bipolar outflow seen pole-on. A non-LTE gaseous origin in an inner disk cannot be excluded but is considered highly unlikely. This direct detection of a significant amount of circumbinary light at optical wavelengths poses several significant questions regarding our understanding of both post-AGB binaries and the physics in their circumbinary disks. Although the identification of the source of emission/scattering remains inconclusive without further study on this and similar objects, the implications are manifold.Comment: Accepted for publication in A&A, 16 pages, 15 figure

Broadening the Debate About Post-trial Access to Medical Interventions: A Qualitative Study of Participant Experiences at the End of a Trial Investigating a Medical Device to Support Type 1 Diabetes Self-Management.

Increasing ethical attention and debate is focusing on whether individuals who take part in clinical trials should be given access to post-trial care. However, the main focus of this debate has been upon drug trials undertaken in low-income settings. To broaden this debate, we report findings from interviews with individuals (n = 24) who participated in a clinical trial of a closed-loop system, which is a medical device under development for people with type 1 diabetes that automatically adjusts blood glucose to help keep it within clinically recommended ranges. Individuals were recruited from UK sites and interviewed following trial close-out, at which point the closed-loop had been withdrawn. While individuals were stoical and accepting of the requirement to return the closed-loop, they also conveyed varying degrees of distress. Many described having relaxed diabetes management practices while using the closed-loop and having become deskilled as a consequence, which made reverting back to pre-trial regimens challenging. Participants also described unanticipated consequences arising from using a closed-loop. As well as deskilling, these included experiencing psychological and emotional benefits that could not be sustained after the closed-loop had been withdrawn and participants reevaluating their pre- and post-trial life in light of having used a closed-loop and now perceiving this life much more negatively. Participants also voiced frustrations about experiencing better blood glucose control using a closed-loop and then having to revert to using what they now saw as antiquated and imprecise self-management tools. We use these findings to argue that ethical debates about post-trial provisioning need to be broadened to consider potential psychological and emotional harms, and not just clinical harms, that may result from withdrawal of investigated treatments. We also suggest that individuals may benefit from information about potential nonclinical harms to help make informed decisions about trial participation.NIHR, JDR

Chaos, containment and change: responding to persistent offending by young people

This article reviews policy developments in Scotland concerning 'persistent young offenders' and then describes the design of a study intended to assist a local planning group in developing its response. The key findings of a review of casefiles of young people involved in persistent offending are reported. It emerges that youth crime and young people involved in offending are more complex and heterogeneous than is sometimes assumed. This, along with a review of some literature about desistance from offending, reaffirms the need for properly individualised interventions. Studies of 'desisters' suggest the centrality of effective and engaging working relationships in this process. However, these studies also re-assert the significance of the social contexts of workers’ efforts to bring 'change' out of 'chaos'. We conclude therefore that the 'new correctionalism' must be tempered with appreciation of the social exclusion of young people who offend

The Long Period, Massive Binaries HD 37366 and HD 54662: Potential Targets for Long Baseline Optical Interferometry

We present the results from an optical spectroscopic analysis of the massive stars HD 37366 and HD 54662. We find that HD 37366 is a double-lined spectroscopic binary with a period of 31.8187 +/- 0.0004 days, and HD 54662 is also a double lined binary with a much longer period of 557.8 +/- 0.3 days. The primary of HD 37366 is classified as O9.5 V, and it contributes approximately two-thirds of the optical flux. The less luminous secondary is a broad-lined, early B-type main-sequence star. Tomographic reconstruction of the individual spectra of HD 37366 reveals absorption lines present in each component, enabling us to constrain the nature of the secondary and physical characteristics of both stars. Tomographic reconstruction was not possible for HD 54662; however, we do present mean spectra from our observations that show that the secondary component is approximately half as bright as the primary. The observed spectral energy distributions (SEDs) were fit with model SEDs and galactic reddening curves to determine the angular sizes of the stars. By assuming radii appropriate for their classifications, we determine distance ranges of 1.4 - 1.9 and 1.2 - 1.5 kpc for HD 37366 and HD 54662, respectively.Comment: 27 pages, 8 figures, Accepted for publication in Ap

Randomized trial comparing proactive, high-dose versus reactive, low-dose intravenous iron supplementation in hemodialysis (PIVOTAL) : Study design and baseline data

Background: Intravenous (IV) iron supplementation is a standard maintenance treatment for hemodialysis (HD) patients, but the optimum dosing regimen is unknown. Methods: PIVOTAL (Proactive IV irOn Therapy in hemodiALysis patients) is a multicenter, open-label, blinded endpoint, randomized controlled (PROBE) trial. Incident HD adults with a serum ferritin 700 μg/L and/or TSAT ≥40%) or a reactive, low-dose IV iron arm (iron sucrose administered if ferritin <200 μg/L or TSAT < 20%). We hypothesized that proactive, high-dose IV iron would be noninferior to reactive, low-dose IV iron for the primary outcome of first occurrence of nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for heart failure or death from any cause. If noninferiority is confirmed with a noninferiority limit of 1.25 for the hazard ratio of the proactive strategy relative to the reactive strategy, a test for superiority will be carried out. Secondary outcomes include infection-related endpoints, ESA dose requirements, and quality-of-life measures. As an event-driven trial, the study will continue until at least 631 primary outcome events have accrued, but the expected duration of follow-up is 2-4 years. Results: Of the 2,589 patients screened across 50 UK sites, 2,141 (83%) were randomized. At baseline, 65.3% were male, the median age was 65 years, and 79% were white. According to eligibility criteria, all patients were on ESA at screening. Prior stroke and MI were present in 8 and 9% of the cohort, respectively, and 44% of patients had diabetes at baseline. Baseline data for the randomized cohort were generally concordant with recent data from the UK Renal Registry. Conclusions: PIVOTAL will provide important information about the optimum dosing of IV iron in HD patients representative of usual clinical practice. Trial Registration: EudraCT number: 2013-002267-25.Peer reviewedFinal Published versio

Young people, crime and school exclusion: a case of some surprises

During the 1990s the number of young people being permanently excluded from schools in England and Wales increased dramatically from 2,910 (1990/91) to a peak of 12,700 (1996/97). Coinciding with this rise was a resurgence of the debate centring on lawless and delinquent youth. With the publication of Young People and Crime (Graham and Bowling 1995) and Misspent Youth (Audit Commission 1996) the 'common sense assumption' that exclusion from school inexorably promoted crime received wide support, with the school excludee portrayed as another latter day 'folk devil'. This article explores the link between school exclusion and juvenile crime, and offers some key findings from a research study undertaken with 56 young people who had experience of being excluded from school. Self-report interview questions reveal that whilst 40 of the young people had offended, 90% (36) reported that the onset of their offending commenced prior to their first exclusion. Moreover, 50 (89.2% of the total number of young people in the sample), stated that they were no more likely to offend subsequent to being excluded and 31 (55.4%) stated that they were less likely to offend during their exclusion period. Often, this was because on being excluded, they were 'grounded' by their parents

Host Star Properties And Transit Exclusion For The HD 38529 Planetary System

The transit signature of exoplanets provides an avenue through which characterization of exoplanetary properties may be undertaken, such as studies of mean density, structure, and atmospheric composition. The Transit Ephemeris Refinement and Monitoring Survey is a program to expand the catalog of transiting planets around bright host stars by refining the orbits of known planets discovered with the radial velocity technique. Here we present results for the HD 38529 system. We determine fundamental properties of the host star through direct interferometric measurements of the radius and through spectroscopic analysis. We provide new radial velocity measurements that are used to improve the Keplerian solution for the two known planets, and we find no evidence for a previously postulated third planet. We also present 12 years of precision robotic photometry of HD 38529 that demonstrate the inner planet does not transit and the host star exhibits cyclic variations in seasonal mean brightness with a timescale of approximately six years