A Novel T Cell Receptor Transgenic Animal Model of Seborrheic Dermatitis-Like Skin Disease

We have characterized a novel animal model of the common inflammatory skin disease seborrheic dermatitis (SD) that involves the expression of the self-specific 2C transgenic T cell receptor on the DBA/2 genetic background. Opportunistic fungal pathogens are present in the primary histological lesions and severe disease can be mitigated by the administration of fluconazole, demonstrating a role for infection in disease pathogenesis. Spontaneous disease convalescence occurs at 70–90 d of age and is preceded by an expansion of CD4+ T cells that partially restores the T cell lymphopenia that occurs in these animals. The adoptive transfer of syngeneic CD4+ T cells into pre-diseased DBA/2 2C mice completely abrogates the development of cutaneous disease. The pattern of disease inheritance in DBA/2 backcrosses suggests that one, or a closely linked group of genes, may control disease penetrance. Bone marrow reconstitution experiments demonstrated that the DBA/2 susceptibility factor(s) governing disease penetrance is likely non-hematopoietic since bone marrow from disease-resistant 2C mice can adoptively transfer the full disease phenotype to non-transgenic DBA/2 animals. This model implicates fungal organisms and CD4+ T cell lymphopenia in the development of a SD-like condition and, as such, may mimic the development of SD in acquired immunodeficiency syndrome

Space Warps II. New Gravitational Lens Candidates from the CFHTLS Discovered through Citizen Science

We report the discovery of 29 promising (and 59 total) new lens candidates from the CFHT Legacy Survey (CFHTLS) based on about 11 million classifications performed by citizen scientists as part of the first Space Warps lens search. The goal of the blind lens search was to identify lens candidates missed by robots (the RingFinder on galaxy scales and ArcFinder on group/cluster scales) which had been previously used to mine the CFHTLS for lenses. We compare some properties of the samples detected by these algorithms to the Space Warps sample and find them to be broadly similar. The image separation distribution calculated from the Space Warps sample shows that previous constraints on the average density profile of lens galaxies are robust. SpaceWarps recovers about 65% of known lenses, while the new candidates show a richer variety compared to those found by the two robots. This detection rate could be increased to 80% by only using classifications performed by expert volunteers (albeit at the cost of a lower purity), indicating that the training and performance calibration of the citizen scientists is very important for the success of Space Warps. In this work we present the SIMCT pipeline, used for generating in situ a sample of realistic simulated lensed images. This training sample, along with the false positives identified during the search, has a legacy value for testing future lens finding algorithms. We make the pipeline and the training set publicly available.Comment: 23 pages, 12 figures, MNRAS accepted, minor to moderate changes in this versio

Placental histology predicted adverse outcomes in extremely premature neonates in Norway-population-based study

Aim We evaluated the role of placental pathology in predicting adverse outcomes for neonates born extremely preterm (EPT) before 28 weeks of gestation. Methods This was a prospective observational study of 123 extremely preterm singletons born in a hospital in western Norway, and the placentas were classified according to the Amsterdam criteria. The associations between histologic chorioamnionitis (HCA), by the presence or the absence of a foetal inflammatory response (FIR+ or FIR−), maternal vascular malperfusion (MVM) as a whole and adverse neonatal outcomes were evaluated by logistic regression analyses. Adverse outcomes were defined as perinatal death, necrotising enterocolitis (NEC), bronchopulmonary dysplasia (BPD), brain pathology by magnetic resonance imaging at term-equivalent age, retinopathy of prematurity and early-onset neonatal sepsis. The results are reported as odds ratios (ORs) with 95% confidence intervals (CIs). Results HCA was associated with NEC (OR 12.2, 95% CI 1.1 to 137.1). HCA/FIR+ was associated with BPD (OR 14.9, 95% CI 1.8–122.3) and brain pathology (OR 9.8, 95% CI 1.4–71.6), but HCA/FIR− was not. The only neonatal outcome that MVM was associated with was low birthweight. Conclusion Placental histology provided important information when assessing the risk of adverse neonatal outcomes following EPT birth.publishedVersio

Space Warps: I. Crowd-sourcing the Discovery of Gravitational Lenses

We describe Space Warps, a novel gravitational lens discovery service that yields samples of high purity and completeness through crowd-sourced visual inspection. Carefully produced colour composite images are displayed to volunteers via a web- based classification interface, which records their estimates of the positions of candidate lensed features. Images of simulated lenses, as well as real images which lack lenses, are inserted into the image stream at random intervals; this training set is used to give the volunteers instantaneous feedback on their performance, as well as to calibrate a model of the system that provides dynamical updates to the probability that a classified image contains a lens. Low probability systems are retired from the site periodically, concentrating the sample towards a set of lens candidates. Having divided 160 square degrees of Canada-France-Hawaii Telescope Legacy Survey (CFHTLS) imaging into some 430,000 overlapping 82 by 82 arcsecond tiles and displaying them on the site, we were joined by around 37,000 volunteers who contributed 11 million image classifications over the course of 8 months. This Stage 1 search reduced the sample to 3381 images containing candidates; these were then refined in Stage 2 to yield a sample that we expect to be over 90% complete and 30% pure, based on our analysis of the volunteers performance on training images. We comment on the scalability of the SpaceWarps system to the wide field survey era, based on our projection that searches of 10$^5$ images could be performed by a crowd of 10$^5$ volunteers in 6 days.Comment: 21 pages, 13 figures, MNRAS accepted, minor to moderate changes in this versio

Stathmin expression associates with vascular and immune responses in aggressive breast cancer subgroups

Studies indicate that stathmin expression associates with PI3K activation in breast cancer, suggesting stathmin as a marker for targetable patient subgroups. Here we assessed stathmin in relation to tumour proliferation, vascular and immune responses, BRCA1 germline status, basal-like differentiation, clinico-pathologic features, and survival. Immunohistochemical staining was performed on breast cancers from two series (cohort 1, n = 187; cohort 2, n = 198), and mass spectrometry data from 24 cases and 12 breast cancer cell lines was examined for proteomic profiles. Open databases were also explored (TCGA, METABRIC, Oslo2 Landscape cohort, Cancer Cell Line Encyclopedia). High stathmin expression associated with tumour proliferation, p53 status, basal-like differentiation, BRCA1 genotype, and high-grade histology. These patterns were confirmed using mRNA data. Stathmin mRNA further associated with tumour angiogenesis, immune responses and reduced survival. By logistic regression, stathmin protein independently predicted a BRCA1 genotype (OR 10.0, p = 0.015) among ER negative tumours. Cell line analysis (Connectivity Map) implied PI3K inhibition in tumours with high stathmin. Altogether, our findings indicate that stathmin might be involved in the regulation of tumour angiogenesis and immune responses in breast cancer, in addition to tumour proliferation. Cell data point to potential effects of PI3K inhibition in tumours with high stathmin expression.publishedVersio

SpaceWarps- II. New gravitational lens candidates from the CFHTLS discovered through citizen science

We report the discovery of 29 promising (and 59 total) new lens candidates from the Canada-France-Hawaii Telescope Legacy Survey (CFHTLS) based on about 11 million classifications performed by citizen scientists as part of the first SpaceWarps lens search. The goal of the blind lens search was to identify lens candidates missed by robots (the ringfinder on galaxy scales and arcfinder on group/cluster scales) which had been previously used to mine the CFHTLS for lenses. We compare some properties of the samples detected by these algorithms to the SpaceWarps sample and find them to be broadly similar. The image separation distribution calculated from the SpaceWarps sample shows that previous constraints on the average density profile of lens galaxies are robust. SpaceWarps recovers about 65 per cent of known lenses, while the new candidates show a richer variety compared to those found by the two robots. This detection rate could be increased to 80 per cent by only using classifications performed by expert volunteers (albeit at the cost of a lower purity), indicating that the training and performance calibration of the citizen scientists is very important for the success of SpaceWarps. In this work we present the SIMCT pipeline, used for generating in situ a sample of realistic simulated lensed images. This training sample, along with the false positives identified during the search, has a legacy value for testing future lens-finding algorithms. We make the pipeline and the training set publicly availabl

SpaceWarps - I. Crowdsourcing the discovery of gravitational lenses

We describe SpaceWarps, a novel gravitational lens discovery service that yields samples of high purity and completeness through crowdsourced visual inspection. Carefully produced colour composite images are displayed to volunteers via a web-based classification interface, which records their estimates of the positions of candidate lensed features. Images of simulated lenses, as well as real images which lack lenses, are inserted into the image stream at random intervals; this training set is used to give the volunteers instantaneous feedback on their performance, as well as to calibrate a model of the system that provides dynamical updates to the probability that a classified image contains a lens. Low-probability systems are retired from the site periodically, concentrating the sample towards a set of lens candidates. Having divided 160 deg2 of Canada-France-Hawaii Telescope Legacy Survey imaging into some 430000 overlapping 82 by 82arcsec tiles and displaying them on the site, we were joined by around 37000 volunteers who contributed 11 million image classifications over the course of eight months. This stage 1 search reduced the sample to 3381 images containing candidates; these were then refined in stage 2 to yield a sample that we expect to be over 90 per cent complete and 30 per cent pure, based on our analysis of the volunteers performance on training images. We comment on the scalability of the SpaceWarps system to the wide field survey era, based on our projection that searches of 105 images could be performed by a crowd of 105 volunteers in 6

The LSST Dark Energy Science Collaboration (DESC) Science Requirements Document

The Large Synoptic Survey Telescope (LSST) Dark Energy Science Collaboration (DESC) will use five cosmological probes: galaxy clusters, large scale structure, supernovae, strong lensing, and weak lensing. This Science Requirements Document (SRD) quantifies the expected dark energy constraining power of these probes individually and together, with conservative assumptions about analysis methodology and follow-up observational resources based on our current understanding and the expected evolution within the field in the coming years. We then define requirements on analysis pipelines that will enable us to achieve our goal of carrying out a dark energy analysis consistent with the Dark Energy Task Force definition of a Stage IV dark energy experiment. This is achieved through a forecasting process that incorporates the flowdown to detailed requirements on multiple sources of systematic uncertainty. Future versions of this document will include evolution in our software capabilities and analysis plans along with updates to the LSST survey strategy.Comment: 32 pages + 60 pages of appendices. This is v1 of the DESC SRD, an internal collaboration document that is being made public and is not planned for submission to a journal. Data products for reproducing key plots are available at the LSST DESC Zenodo community, https://zenodo.org/communities/lsst-desc; see "Executive Summary and User Guide" for instructions on how to use and cite those product

Variation in neurosurgical management of traumatic brain injury

Background: Neurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe. Methods: A survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP). Results: The survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30 min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25 mmHg, 18% 30 mmHg, and 17% 20 mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions. Conclusion: Despite a homogeneous organization, considerable practice variation exists of neurosurgical strategies for TBI in Europe. These results provide an incentive for comparative effectiveness research to determine elements of effective neurosurgical care

Large share price movements, the disclosure of news and corporate governance: Implications for disclosure rules

Purpose The paper aims to examine the link between firm‐level large share price movements, firm‐specific company announcements and corporate governance. Stock market regulation in the UK requires firms to disclose new price‐sensitive information immediately via official news providers. The paper investigates whether large share price movements are accompanied by firm disclosure. It also investigates whether corporate governance attributes influence the degree of disclosure by firms. Design/methodology/approach The disclosure measure is constructed by identifying the largest abnormal daily stock returns for sample firms, and then firm‐specific announcements in the three‐day window centred on the abnormal return day are searched. Corporate governance variables known to influence disclosure practice are then collected and tested to ascertain whether they influence disclosure for positive and negative (good and bad announcements) abnormal returns. Findings Large share price movements are accompanied by an official share price movement in 45.2 per cent of cases. This rises to 62.9 per cent when new analyst or newspaper articles are included as potential drivers of the abnormal share price return. The higher the proportion of non‐executive directors and CEO/chair duality lead to a higher incidence of bad news disclosure, suggesting increased scrutiny works. The higher the level of CEO and board ownership the lower the level of disclosure. Finally, institutional ownership concentration appears to negatively influence the level of disclosure. Originality/value Higher levels of corporate governance are shown to lead to better firm disclosure. At the same time, the authors find that in almost 40 per cent of large abnormal share price returns no information has come to the market to drive the share price. Thus, the paper has important messages for regulators, who need to investigate why prices often move a long way without accompanying news. Shareholders, particularly institutions, should ensure high levels of disclosure by company directors.</p