Rechallenge patients with immune checkpoint inhibitors following severe immune-related adverse events: review of the literature and suggested prophylactic strategy.

Patients with cancer who developed severe, grade 3 or 4 immune-related adverse events (irAEs) during therapy with immune checkpoint inhibitors are at risk for developing severe toxicities again on rechallenge with checkpoint inhibitors. Consequently, medical oncologists and multidisciplinary teams are hesitant to retreat in this scenario, despite the fact that a number of patients may derive clinical benefit from this approach. Balancing such clinical benefit and treatment-related toxicities for each patient is becoming increasingly challenging as more and more patients with cancer are being treated with checkpoint inhibitors. In this manuscript, we provide an extensive overview of the relevant literature on retreatment after toxicity, and suggest prophylactic approaches to minimize the risk of severe irAE following rechallenge with immune checkpoint blockade, since treatment may be lifesaving in a number of occasions

Developing sustainability learning in business school curricula–productive boundary objects and participatory processes

© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. Sustainability learning is holistic and complex as it draws on diverse disciplines and can be interpreted differently within individual pedagogies. Embedding sustainability across and within business schools relies on developing suitable boundary objects. These may include representations such as models, frameworks or classificatory schemes that are malleable enough to be adapted for use within the disparate disciplines and pedagogies, yet durable enough to be recognisable and to maintain consistency across them. Boundary objects thus allow the sharing of ways of knowing or practice across various social boundaries. This paper outlines how participatory curriculum development processes can enable sustainability to be embedded in a business school curriculum. Distinct phases of the process were marked by different ways of knowing, as disciplinary-specific academics developed and embedded sustainability into and across curricula. Boundary objects were both outcomes and productive facilitators of this process. They acted as catalysts and attracted ongoing processes of dialogue, debate and meaning-making between these academics. The institutional context provided enabling conditions to legitimize outcomes from the participatory process. The process may be replicable in other business schools by the use of boundary objects

Risk Factors for Soil-Transmitted Helminth Infections during the First 3 Years of Life in the Tropics; Findings from a Birth Cohort.

Background: Soil-transmitted helminths (STH) infect more than 2 billion humans worldwide, causing significant morbidity in children. There are few data on the epidemiology and risk factors for infection in pre-school children. To investigate risk factors for infection in early childhood, we analysed data prospectively collected in the ECUAVIDA birth cohort in Ecuador. Methods and Findings: Children were recruited at birth and followed up to 3 years of age with periodic collection of stool samples that were examined microscopically for STH parasites. Data on social, demographic, and environmental risk factors were collected from the mother at time of enrolment. Associations between exposures and detection of STH infections were analysed by multivariable logistic regression. Data were analysed from 1,697 children for whom a stool sample was obtained at 3 years. 42.3% had at least one STH infection in the first 3 years of life and the most common infections were caused by A. lumbricoides (33.2% of children) and T. trichiura (21.2%). Hookworm infection was detected in 0.9% of children. Risk of STH infection was associated with factors indicative of poverty in our study population such as Afro-Ecuadorian ethnicity and low maternal educational level. Maternal STH infections during pregnancy were strong risk factors for any childhood STH infection, infections with either A. lumbricoides or T. trichiura, and early age of first STH infection. Children of mothers with moderate to high infections intensities with A. lumbricoides were most at risk. Conclusions: Our data show high rates of infection with STH parasites during the first 3 years of life in an Ecuadorian birth cohort, an observation that was strongly associated with maternal STH infections during pregnancy. The targeted treatment of women of childbearing age, in particular before pregnancy, with anthelmintic drugs could offer a novel approach to the prevention of STH infections in pre-school children

Palliative care in UK prisons: practical and emotional challenges for staff and fellow prisoners

Despite falling crime rates in England and Wales over the past 20 years, the number of prisoners has doubled. People over the age of 50 constitute the fastest growing section of the prison population, and increasing numbers of older prisoners are dying in custody. This article discusses some of the issues raised by these changing demographics and draws on preliminary findings from a study underway in North West England. It describes the context behind the rise in the numbers of older prisoners; explores the particular needs of this growing population; and discusses some of the practical and emotional challenges for prison officers, health care staff, and fellow prisoners who are involved in caring for dying prisoners in a custodial environment

A near-infrared study of AGB and red giant stars in the Leo I dSph galaxy

A near-infrared imaging study of the evolved stellar populations in the dwarf spheroidal galaxy Leo I is presented. Based on JHK observations obtained with the WFCAM wide-field array at the UKIRT telescope, we build a near-infrared photometric catalogue of red giant branch (RGB) and asymptotic giant branch (AGB) stars in Leo I over a 13.5 arcmin square area. The V-K colours of RGB stars, obtained by combining the new data with existing optical observations, allow us to derive a distribution of global metallicity [M/H] with average [M/H] = -1.51 (uncorrected) or [M/H] = -1.24 +/- 0.05 (int) +/- 0.15 (syst) after correction for the mean age of Leo I stars. This is consistent with the results from spectroscopy once stellar ages are taken into account. Using a near-infrared two-colour diagram, we discriminate between carbon- and oxygen-rich AGB stars and obtain a clean separation from Milky Way foreground stars. We reveal a concentration of C-type AGB stars relative to the red giant stars in the inner region of the galaxy, which implies a radial gradient in the intermediate-age (1-3 Gyr) stellar populations. The numbers and luminosities of the observed carbon- and oxygen-rich AGB stars are compared with those predicted by evolutionary models including the thermally-pulsing AGB phase, to provide new constraints to the models for low-metallicity stars. We find an excess in the predicted number of C stars fainter than the RGB tip, associated to a paucity of brighter ones. The number of O-rich AGB stars is roughly consistent with the models, yet their predicted luminosity function is extended to brighter luminosity. It appears likely that the adopted evolutionary models overestimate the C star lifetime and underestimate their K-band luminosity.Comment: MNRAS, accepte

Discovery of the optical counterpart and early optical observations of GRB990712

We present the discovery observations of the optical counterpart of the gamma-ray burster GRB990712 taken 4.16 hours after the outburst and discuss its light curve observed in the V, R and I bands during the first ~35 days after the outburst. The observed light curves were fitted with a power-law decay for the optical transient (OT), plus an additional component which was treated in two different ways. First, the additional component was assumed to be an underlying galaxy of constant brightness. The resulting slope of the decay is 0.97+/-0.05 and the magnitudes of the underlying galaxy are: V = 22.3 +/- 0.05, R = 21.75 +/- 0.05 and I = 21.35 +/- 0.05. Second, the additional component was assumed to be a galaxy plus an underlying supernova with a time-variable brightness identical to that of GRB980425, appropriately scaled to the redshift of GRB990712. The resulting slope of the decay is similar, but the goodness-of-fit is worse which would imply that either this GRB is not associated with an underlying supernova or the underlying supernova is much fainter than the supernova associated with GRB980425. The galaxy in this case is fainter: V = 22.7 +/- 0.05, R = 22.25 +/- 0.05 and I = 22.15 +/- 0.05; and the OT plus the underlying supernova at a given time is brighter. Measurements of the brightnesses of the OT and the galaxy by late-time HST observation and ground-based observations can thus assess the presence of an underlying supernova.Comment: To appear in Ap

Limb-Darkening of a K Giant in the Galactic Bulge: PLANET Photometry of MACHO 97-BLG-28

We present the PLANET photometric dataset for the binary-lens microlensing event MACHO 97-BLG-28 consisting of 696 I and V-band measurements, and analyze it to determine the radial surface brightness profile of the Galactic bulge source star. The microlensed source, demonstrated to be a K giant by our independent spectroscopy, crossed the central isolated cusp of the lensing binary, generating a sharp peak in the light curve that was well-resolved by dense (3 - 30 minute) and continuous monitoring from PLANET sites in Chile, South Africa, and Australia. Our modeling of these data has produced stellar profiles for the source star in the I and V bands that are in excellent agreement with those predicted by stellar atmospheric models for K giants. The limb-darkening coefficients presented here are the first derived from microlensing, among the first for normal giants by any technique, and the first for any star as distant as the Galactic bulge. Modeling indicates that the lensing binary has a mass ratio q = 0.23 and an (instantaneous) separation in units of the angular Einstein ring radius of d = 0.69 . For a lens in the Galactic bulge, this corresponds to a typical stellar binary with a projected separation between 1 and 2 AU. If the lens lies closer, the separation is smaller, and one or both of the lens objects is in the brown dwarf regime. Assuming that the source is a bulge K2 giant at 8 kpc, the relative lens-source proper motion is mu = 19.4 +/- 2.6 km/s /kpc, consistent with a disk or bulge lens. If the non-lensed blended light is due to a single star, it is likely to be a young white dwarf in the bulge, consistent with the blended light coming from the lens itself.Comment: 32 Pages, including 1 table and 9 postscript figures. (Revised version has slightly modified text, corrected typo, and 1 new figure.) Accepted for publication in 1999 Astrophysical Journal; data are now available at http://www.astro.rug.nl/~plane

Towards A Census of Earth-mass Exo-planets with Gravitational Microlensing

Thirteen exo-planets have been discovered using the gravitational microlensing technique (out of which 7 have been published). These planets already demonstrate that super-Earths (with mass up to ~10 Earth masses) beyond the snow line are common and multiple planet systems are not rare. In this White Paper we introduce the basic concepts of the gravitational microlensing technique, summarise the current mode of discovery and outline future steps towards a complete census of planets including Earth-mass planets. In the near-term (over the next 5 years) we advocate a strategy of automated follow-up with existing and upgraded telescopes which will significantly increase the current planet detection efficiency. In the medium 5-10 year term, we envision an international network of wide-field 2m class telescopes to discover Earth-mass and free-floating exo-planets. In the long (10-15 year) term, we strongly advocate a space microlensing telescope which, when combined with Kepler, will provide a complete census of planets down to Earth mass at almost all separations. Such a survey could be undertaken as a science programme on Euclid, a dark energy probe with a wide-field imager which has been proposed to ESA's Cosmic Vision Programme.Comment: 10 pages. White Paper submission to the ESA Exo-Planet Roadmap Advisory Team. See also "Inferring statistics of planet populations by means of automated microlensing searches" by M. Dominik et al. (arXiv:0808.0004