Impaired interferon-γ responses, increased interleukin-17 expression, and a tumor necrosis factor–α transcriptional program in invasive aspergillosis

This article is available open access through the publisher’s website. Copyright @ 2009 Oxford University Press.Background - Invasive aspergillosis (IA) is the most common cause of death associated with fungal infection in the developed world. Historically, susceptibility to IA has been associated with prolonged neutropenia; however, IA has now become a major problem in patients on calcineurin inhibitors and allogenic hematopoetic stem cell transplant patients following engraftment. These observations suggest complex cellular mechanisms govern immunity to IA. Methods - To characterize the key early events that govern outcome from infection with Aspergillus fumigatus we performed a comparative immunochip microarray analysis of the pulmonary transcriptional response to IA between cyclophosphamide-treated mice and immunocompetent mice at 24 h after infection. Results - We demonstrate that death due to infection is associated with a failure to generate an incremental interferon-γ response, increased levels of interleukin-5 and interleukin-17a transcript, coordinated expression of a network of tumor necrosis factor–α-related genes, and increased levels of tumor necrosis factor–α. In contrast, clearance of infection is associated with increased expression of a number genes encoding proteins involved in innate pathogen clearance, as well as apoptosis and control of inflammation. Conclusion - This first organ-level immune response transcriptional analysis for IA has enabled us to gain new insights into the mechanisms that govern fungal immunity in the lung.The BBSRC, CGD Research Trust, and the MRC

The [OIII]λ5007 equivalent width distribution at z ∼2: The redshift evolution of the extreme emission line galaxies

We determine the [OIII]$\lambda5007$ equivalent width (EW) distribution of $1.700<\rm{z}<2.274$ rest-frame UV-selected (M$_{\rm{UV}}<-19$) star-forming galaxies in the GOODS North and South fields. We make use of deep HDUV broadband photometry catalogues for selection and 3D-HST WFC3/IR grism spectra for measurement of line properties. The [OIII]$\lambda5007$ EW distribution allows us to measure the abundance of extreme emission line galaxies (EELGs) within this population. We model a log-normal distribution to the [OIII]$\lambda5007$ rest-frame equivalent widths of galaxies in our sample, with location parameter $\mu=4.24\pm0.07$ and variance parameter $\sigma= 1.33\pm0.06$. This EW distribution has a mean [OIII]$\lambda5007$ EW of 168$\pm1\r{A}$. The fractions of $\rm{z}\sim2$ rest-UV-selected galaxies with [OIII]$\lambda5007$ EWs greater than $500, 750$ and $1000\r{A}$ are measured to be $6.8^{+1.0}_{-0.9}\%$, $3.6^{+0.7}_{-0.6}\%$, and $2.2^{+0.5}_{-0.4}\%$ respectively. The EELG fractions do not vary strongly with UV luminosity in the range ($-21.6<M_{\rm{UV}}<-19.0$) considered in this paper, consistent with findings at higher redshifts. We compare our results to $\rm{z}\sim5$ and $\rm{z}\sim7$ studies where candidate EELGs have been discovered through Spitzer/IRAC colours, and we identify rapid evolution with redshift in the fraction of star-forming galaxies observed in an extreme emission line phase (a rise by a factor $\sim10$ between $\rm{z}\sim2$ and $\rm{z}\sim7$). This evolution is consistent with an increased incidence of strong bursts in the galaxy population of the reionisation era. While this population makes a sub-dominant contribution of the ionising emissivity at $\rm{z}\simeq2$, EELGs are likely to dominate the ionising output in the reionisation era

Multi-Professional Perspectives on Adolescent and Young Adult Oncology Across Europe: An e-Delphi Survey

The aims of this article are to describe the ongoing development of adolescent and young adult (AYA) cancer services within the European Union (EU), and to develop consensus on key areas within the field. This survey used an e-Delphi design. An initial survey was distributed via email to professionals working in Europe. A snowball sampling technique was used to promote distribution. Consensus was sought over three rounds from October 2012 to April 2015. Consensus was defined as >80% agreement (“agree” or “strongly agree”). Sixty professionals participated in round 1, 106 in round 2, and 61 in round 3. Twenty-six countries were represented across all rounds. Consensus was achieved for: the need for national policy guidance, the importance of patient choice, the validity of the International Charter of Rights for Young People, and some aspects of multi-disciplinary working. There was 75% agreement on a single definition of the patient age range within AYA cancer care. European professionals with expertise in AYA cancer care reached consensus on key elements of care for this group. The optimal AYA age range remained an elusive topic on which to agree. The broad engagement and interest in AYA cancer across the EU through the European Network for Cancer in Children and Adolescents (ENCCA) network was also demonstrated

Mapping UV properties throughout the cosmic horseshoe: Lessons from VLT-MUSE

We present the first spatially-resolved rest-frame UV study of the gravitationally lensed galaxy, the 'Cosmic Horseshoe' (J1148+1930) at z=2.38. Our gravitational lens model shows that the system is made up of four star-forming regions, each ~4-8 kpc^2 in size, from which we extract four spatially exclusive regional spectra. We study the interstellar and wind absorption lines, along with CIII] doublet emission lines, in each region to investigate any variation in emission/absorption line properties. The mapped CIII] emission shows distinct kinematical structure, with velocity offsets of ~+/-50 km/s between regions suggestive of a merging system, and a variation in equivalent width that indicates a change in ionisation parameter and/or metallicity between the regions. Absorption line velocities reveal a range of outflow strengths, with gas outflowing between -200<v(km/s)<-50 relative to the systemic velocity of that region. Interestingly, the strongest gas outflow appears to emanate from the most diffuse star-forming region. The star-formation rates remain relatively constant (~8-16 M_sol/yr), mostly due to large uncertainties in reddening estimates. As such, the outflows appear to be 'global' rather than 'locally' sourced. We measure electron densities with a range of log(Ne)=3.92-4.36 cm^-3, and point out that such high densities may be common when measured using the CIII] doublet due to its large critical density. Overall, our observations demonstrate that while it is possible to trace variations in large scale gas kinematics, detecting inhomogeneities in physical gas properties and their effects on the outflowing gas may be more difficult. This study provides important lessons for the spatially-resolved rest-frame UV studies expected with future observatories, such as JWST.BLJ thanks support from the European Space Agency (ESA) and SC acknowledges nancial support from the Science & Technology Facilities Council (STFC). The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement no. 308024

Sondeo arqueológico del sector 36 [Material gráfico]

Detalle de los trabajos del levantamiento de materiales arqueológicos del Sector 36 Corte A/C-8/10Copia digital. Madrid : Ministerio de Educación, Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 201

Mean Hα+[N ii]+[S ii] EW inferred for star-forming galaxies at z ∼ 5.1–5.4 using high-quality Spitzer /IRAC photometry

Recent Spitzer/InfraRed Array Camera (IRAC) photometric observations have revealed that rest-frame optical emission lines contribute significantly to the broad-band fluxes of high-redshift galaxies. Specifically, in the narrow redshift range z ∼ 5.1–5.4 the [3.6]–[4.5] colour is expected to be very red, due to contamination of the 4.5 μm band by the dominant Hα line, while the 3.6 μm filter is free of nebular emission lines. We take advantage of new reductions of deep Spitzer/IRAC imaging over the Great Observatories Origins Deep Survey-North+South fields (Labbé et al. 2015) to obtain a clean measurement of the mean Hα equivalent width (EW) from the [3.6]–[4.5] colour in the redshift range z = 5.1–5.4. The selected sources either have measured spectroscopic redshifts (13 sources) or lie very confidently in the redshift range z = 5.1–5.4 based on the photometric redshift likelihood intervals (11 sources). Our zphot = 5.1–5.4 sample and zspec = 5.10–5.40 spectroscopic sample have a mean [3.6]–[4.5] colour of 0.31 ± 0.05 and 0.35 ± 0.07 mag, implying a rest-frame EW (Hα+[N II]+[S II]) of 665 ± 53 and 707 ± 74 Å, respectively, for sources in these samples. These values are consistent albeit slightly higher than derived by Stark et al. at z ∼ 4, suggesting an evolution to higher values of the Hα+[N II]+[S II] EW at z > 2. Using the 3.6 μm band, which is free of emission line contamination, we perform robust spectral energy distribution fitting and find a median specific star formation rate of sSFR = 17+2−517−5+2 Gyr−1, 7+1−2×7−2+1× higher than at z ∼ 2. We find no strong correlation (<2σ) between the Hα+[N II]+[S II] EW and the stellar mass of sources. Before the advent of JWST, improvements in these results will come through an expansion of current spectroscopic samples and deeper Spitzer/IRAC measurements

Spectroscopy of an extreme [OIII] emitting active galactic nucleus at z = 3.212: implications for the reionisation era

Reionization-era galaxies often display intense nebular emission lines, both in rest-frame optical ([O III] + H β) and ultraviolet (UV; C III], C IV). How such strong nebular emission is powered remains unclear, with both active galactic nuclei (AGNs) and hot stars considered equally viable. The UV continuum slopes of these early systems tend to be very blue (β −1) than typical star-forming systems in the reionization era. To investigate the properties of AGNs in the reionization era, we have conducted a search for potential examples of rare analogues with blue continua at intermediate redshift (⁠z ∼ 2−3). Our goals are to determine whether AGNs with intense line emission and blue continua exist and thereby to establish the range of rest-frame UV and optical line ratios in this population. In this paper, we report the detection of an X-ray luminous AGN at z = 3.21 (UDS-24561) with extreme [O III] + H β line emission (equivalent width = 1300 Å) and a blue UV continuum slope (β = −2.34). MMT/Binospec and Keck/MOSFIRE spectra indicate rest-frame UV line ratios consistent with AGN photoionization models and rest-frame optical lines with both a narrow component [full width at half-maximum (FWHM) =154kms−1] and extended broad wings (FWHM =977kms−1⁠), consistent with outflowing gas. We describe how such objects can be identified in future James Webb Space Telescope emission line surveys in the reionization era, thereby providing a valuable census of AGN activity at z > 6 and understanding their contribution to cosmic reionization

Access to Principal Treatment Centres and survival rates for children and young people with cancer in Yorkshire, UK

Background: Principal Treatment Centres (PTC) were established to provide age-appropriate care as well as clinical expertise for children and young people with cancer. However, little is known about the effects of specialist treatment centres on survival outcomes especially for teenagers and young adults. This population-based study aimed to describe access to PTC and the associated trends in survival for 0–24 year olds accounting for stage of disease at presentation and treatment. Methods: Patients diagnosed from 1998–2009 aged 0–24 years were extracted from the Yorkshire Specialist Register of Cancer in Children and Young People, including information on all treating hospitals, followed-up until 31st December 2014. The six commonest cancer types were included: leukaemia (n = 684), lymphoma (n = 558), CNS tumours (n = 547), germ cell tumours (n = 364), soft tissue sarcomas (n = 171) and bone tumours (n = 163). Treatment was categorised into three groups: ‘all’, ‘some’ or ‘no’ treatment received at a PTC. Treatment at PTC was examined by diagnostic group and patient characteristics. Overall survival was modelled using Cox regression adjusting for case-mix including stage, treatment and other socio-demographic and clinical characteristics. Results: Overall 72% of patients received all their treatment at PTC whilst 13% had no treatment at PTC. This differed by diagnostic group and age at diagnosis. Leukaemia patients who received no treatment at PTC had an increased risk of death which was partially explained by differences in patient case-mix (adjusted Hazard Ratio (HR) = 1.73 (95%CI 0.98–3.04)). Soft tissue sarcoma patients who had some or no treatment at PTC had better survival outcomes, which remained after adjustment for patient case-mix (adjusted HR = 0.48 (95%CI 0.23–0.99)). There were no significant differences in outcomes for other diagnostic groups (lymphoma, CNS tumours, bone tumours and germ cell tumours). For leukaemia patients survival outcomes for low risk patients receiving no treatment at PTC were similar to high risk patients who received all treatment at PTC, implying a benefit for care at the PTC. Conclusion: This study demonstrates that for leukaemia patients receiving treatment at a PTC is associated with improved survival that may compensate for a poorer prognosis presentation. However, further information on risk factors is needed for all diagnostic groups in order to fully account for differences in patient case-mix

Description of the BRIGHTLIGHT cohort: the evaluation of teenage and young adult cancer services in England

Objective International recognition of the unique needs of young people with cancer is growing. Many countries have developed specialist age-appropriate cancer services believing them to be of value. In England, 13 specialist principal treatment centres (PTCs) deliver cancer care to young people. Despite this expansion of specialist care, systematic investigation of associated outcomes and costs has, to date, been lacking. The aim of this paper is to describe recruitment and baseline characteristics of the BRIGHTLIGHT cohort and the development of the bespoke measures of levels of care and disease severity, which will inform the evaluation of cancer services in England. Design Prospective, longitudinal, observational study. Setting Ninety-seven National Health Service hospitals in England. Participants A total of 1114 participants were recruited and diagnosed between July 2012 and December 2014: 55% (n=618) were men, mean age was 20.1 years (SD=3.3), most (86%) were white and most common diagnoses were lymphoma (31%), germ cell tumour (19%) and leukaemia (13%). Results At diagnosis, median quality of life score was significantly lower than a published control threshold (69.7 points); 40% had borderline to severe anxiety, and 21% had borderline to severe depression. There was minimal variation in other patient-reported outcomes according to age, diagnosis or severity of illness. Survival was lower in the cohort than for young people diagnosed during the same period who were not recruited (cumulative survival probability 4 years after diagnosis: 88% vs 92%). Conclusions Data collection was completed in March 2018. Longitudinal comparisons will determine outcomes and costs associated with access/exposure to PTCs. Findings will inform international intervention and policy initiatives to improve outcomes for young people with cancer