Diffuse Extragalactic Background Radiation

Attenuation of high--energy gamma rays by pair--production with UV, optical and IR background photons provides a link between the history of galaxy formation and high--energy astrophysics. We present results from our latest semi-analytic models (SAMs), based upon a $\Lambda$CDM hierarchical structural formation scenario and employing all ingredients thought to be important to galaxy formation and evolution, as well as reprocessing of starlight by dust to mid- and far-IR wavelengths. Our models also use results from recent hydrodynamic galaxy merger simulations. These latest SAMs are successful in reproducing a large variety of observational constraints such as number counts, luminosity and mass functions, and color bimodality. We have created 2 models that bracket the likely ranges of galaxy emissivities, and for each of these we show how the optical depth from pair--production is affected by redshift and gamma-ray energy. We conclude with a discussion of the implications of our work, and how the burgeoning science of gamma-ray astronomy will continue to help constrain cosmology.Comment: 12 pages, 8 figures, to be published in the Proceedings of the 4th Heidelberg International Symposium on High Energy Gamma-Ray Astronomy, held July 2008 in Heidelberg, German

Modeling Gamma-Ray Attenuation in High-Redshift GeV Spectra

We present two models for the cosmological UV background light, and calculate the opacity of GeV gamma--rays out to redshift 9. The contributors to the background include 2 possible quasar emissivities, and output from star--forming galaxies as determined by recent a semi--analytic model (SAM) of structure formation. The SAM used in this work is based upon a hierarchical build-up of structure in a $\Lambda$CDM universe and is highly successful in reproducing a variety of observational parameters. Above 1 Rydberg energy, ionizing radiation is subject to reprocessing by the IGM, which we treat using our radiative transfer code, CUBA. The two models for quasar emissivity differing above z = 2.3 are chosen to match the ionization rates observed using flux decrement analysis and the higher values of the line-of-sight proximity effect. We also investigate the possibility of a flat star formation rate density at z $>5$. We conclude that observations of gamma--rays from 10 to 100 GeV by Fermi (GLAST) and the next generation of ground based experiments should confirm a strongly evolving opacity from $1<$ z $<4$. Observation of attenuation in the spectra of gamma--ray bursts at higher redshift could constrain emission of UV radiation at these early times, either from a flat or increasing star-formation density or an unobserved population of sources.Comment: 4 pages, 7 figures, To be published in the Proceedings of the 4th Heidelberg International Symposium on High Energy Gamma-Ray Astronomy, held July 2008 in Heidelberg, German

Genomic Profiling in Luminal Breast Cancer

The developments in gene expression analysis have made it possible tosub-classify hormone receptor-positive (luminal) breast cancer indifferent prognostic subgroups. This sub-classification is currentlyused in clinical routine as prognostic signature (e. g. 21-gene OnoctypeDX (R), 70-gene Mammaprint (R)). As yet, the optimal method forsub-classification has not been defined. Moreover, there is no evidencefrom prospective trials. This review explores widely used genomicsignatures in luminal breast cancer, making a critical appraisal ofevidence from retrospective/prospective trials. It is based onsystematic literature search performed using Medline (accessed September2013) and abstracts presented at the Annual Meeting of American Societyof Clinical Oncology and San Antonio Breast Cancer Symposium

Understanding the structure and functioning of polar pelagic ecosystems to predict the impacts of change

The determinants of the structure, functioning and resilience of pelagic ecosystems across most of the polar regions are not well known. Improved understanding is essential for assessing the value of biodiversity and predicting the effects of change (including in biodiversity) on these ecosystems and the services they maintain. Here we focus on the trophic interactions that underpin ecosystem structure, developing comparative analyses of how polar pelagic food webs vary in relation to the environment. We highlight that there is not a singular, generic Arctic or Antarctic pelagic food web, and, although there are characteristic pathways of energy flow dominated by a small number of species, alternative routes are important for maintaining energy transfer and resilience. These more complex routes cannot, however, provide the same rate of energy flow to highest trophic-level species. Food-web structure may be similar in different regions, but the individual species that dominate mid-trophic levels vary across polar regions. The characteristics (traits) of these species are also different and these differences influence a range of food-web processes. Low functional redundancy at key trophic levels makes these ecosystems particularly sensitive to change. To develop models for projecting responses of polar ecosystems to future environmental change, we propose a conceptual framework that links the life histories of pelagic species and the structure of polar food webs

Genomic Profiling in Luminal Breast Cancer

The developments in gene expression analysis have made it possible tosub-classify hormone receptor-positive (luminal) breast cancer indifferent prognostic subgroups. This sub-classification is currentlyused in clinical routine as prognostic signature (e. g. 21-gene OnoctypeDX (R), 70-gene Mammaprint (R)). As yet, the optimal method forsub-classification has not been defined. Moreover, there is no evidencefrom prospective trials. This review explores widely used genomicsignatures in luminal breast cancer, making a critical appraisal ofevidence from retrospective/prospective trials. It is based onsystematic literature search performed using Medline (accessed September2013) and abstracts presented at the Annual Meeting of American Societyof Clinical Oncology and San Antonio Breast Cancer Symposium

A Synergistic Approach for Evaluating Climate Model Output for Ecological Applications

Increasing concern about the impacts of climate change on ecosystems is prompting ecologists and ecosystem managers to seek reliable projections of physical drivers of change. The use of global climate models in ecology is growing, although drawing ecologically meaningful conclusions can be problematic. The expertise required to access and interpret output from climate and earth system models is hampering progress in utilizing them most effectively to determine the wider implications of climate change. To address this issue, we present a joint approach between climate scientists and ecologists that explores key challenges and opportunities for progress. As an exemplar, our focus is the Southern Ocean, notable for significant change with global implications, and on sea ice, given its crucial role in this dynamic ecosystem. We combined perspectives to evaluate the representation of sea ice in global climate models. With an emphasis on ecologically-relevant criteria (sea ice extent and seasonality) we selected a subset of eight models that reliably reproduce extant sea ice distributions. While the model subset shows a similar mean change to the full ensemble in sea ice extent (approximately 50% decline in winter and 30% decline in summer), there is a marked reduction in the range. This improved the precision of projected future sea ice distributions by approximately one third, and means they are more amenable to ecological interpretation. We conclude that careful multidisciplinary evaluation of climate models, in conjunction with ongoing modeling advances, should form an integral part of utilizing model output. © 2017 Cavanagh, Murphy, Bracegirdle, Turner, Knowland, Corney, Smith, Waluda, Johnston, Bellerby, Constable, Costa, Hofmann, Jackson, Staniland, Wolf-Gladrow, Xavier

Poor glycaemic control is associated with reduced exercise performance and oxygen economy during cardio-pulmonary exercise testing in people with type 1 diabetes

BackgroundTo explore the impact of glycaemic control (HbA1c) on functional capacity during cardio-pulmonary exercise testing in people with type 1 diabetes.MethodsSixty-four individuals with type 1 diabetes (age: 34 ± 8 years; 13 females, HbA1c: 7.8 ± 1% (62 ± 13 mmol/mol), duration of diabetes: 17 ± 9 years) performed a cardio-pulmonary cycle ergometer exercise test until volitional exhaustion. Stepwise linear regression was used to explore relationships between HbA1c and cardio-respiratory data with p ≤ 0.05. Furthermore, participants were divided into quartiles based on HbA1c levels and cardio-respiratory data were analysed by one-way ANOVA. Multiple regression analysis was performed to explore the relationships between changes in time to exhaustion and cardio-respiratory data. Data were adjusted for confounder.ResultsHbA1c was related to time to exhaustion and oxygen consumption at the power output elicited at the sub-maximal threshold of the heart rate turn point (r = 0.47, R2 = 0.22, p = 0.03). Significant differences were found at time to exhaustion between QI vs. QIV and at oxygen consumption at the power output elicited at the heart rate turn point between QI vs. QII and QI vs. QIV (p < 0.05). Changes in oxygen uptake, power output and in oxygen consumption at the power output elicited at the heart rate turn point and at maximum power output explained 55% of the variance in time to exhaustion (r = 0.74, R2 = 0.55, p < 0.01).ConclusionsPoor glycaemic control is related to less economical use of oxygen at sub-maximal work rates and an earlier time to exhaustion during cardio-pulmonary exercise testing. However, exercise training could have the same potential to counteract the influence of poor glycaemic control on functional capacity

Systematic Review: Monoclonal Antibody-Induced Subacute Cutaneous Lupus Erythematosus.

BACKGROUND: Subacute cutaneous lupus erythematosus (SCLE) lacks consensus diagnostic criteria and the pathogenesis is poorly understood. There are increasing reports of SCLE induced by monoclonal antibodies (mAbs), but there are limited data on the aetiology, clinical characteristics and natural course of this disease. METHODS: We devised a set of diagnostic criteria for SCLE in collaboration with a multinational, multispecialty panel. This systematic review employed a two-layered search strategy of five databases for cases of mAb-induced SCLE (PROSPERO registered protocol CRD42019116521). To explore the relationship between relative mAb use and the number of SCLE cases reported, the estimated number of mAb users was modelled from 2013 to 2018 global commercial data and estimated annual therapy costs. RESULTS: From 40 papers, we identified 52 cases of mAb-induced SCLE, occurring in a cohort that was 73% female and with a median age of 61 years. Fifty percent of cases were induced by anti-tumour necrosis factor (TNF)-ɑ agents. A median of three drug doses preceded SCLE onset and the lesions lasted a median of 7 weeks after drug cessation. Oral and topical corticosteroids were most frequently used. Of the licensed mAbs, adalimumab, denosumab, rituximab, etanercept and infliximab were calculated to have the highest relative number of yearly users based on global sales data. Comparing the number of mAb-induced SCLE cases with estimated yearly users, the checkpoint inhibitors pembrolizumab and nivolumab showed strikingly high rates of SCLE relative to their global use, but ipilimumab did not. CONCLUSION: We present the first systematic review characterising mAb-induced SCLE with respect to triggers, clinical signs, laboratory findings, prognosis and treatment approaches. We identify elevated rates associated with the use of checkpoint inhibitors and anti-TNFɑ agents

Systematic Review: Monoclonal Antibody-Induced Subacute Cutaneous Lupus Erythematosus

Abstract: Background: Subacute cutaneous lupus erythematosus (SCLE) lacks consensus diagnostic criteria and the pathogenesis is poorly understood. There are increasing reports of SCLE induced by monoclonal antibodies (mAbs), but there are limited data on the aetiology, clinical characteristics and natural course of this disease. Methods: We devised a set of diagnostic criteria for SCLE in collaboration with a multinational, multispecialty panel. This systematic review employed a two-layered search strategy of five databases for cases of mAb-induced SCLE (PROSPERO registered protocol CRD42019116521). To explore the relationship between relative mAb use and the number of SCLE cases reported, the estimated number of mAb users was modelled from 2013 to 2018 global commercial data and estimated annual therapy costs. Results: From 40 papers, we identified 52 cases of mAb-induced SCLE, occurring in a cohort that was 73% female and with a median age of 61 years. Fifty percent of cases were induced by anti-tumour necrosis factor (TNF)-ɑ agents. A median of three drug doses preceded SCLE onset and the lesions lasted a median of 7 weeks after drug cessation. Oral and topical corticosteroids were most frequently used. Of the licensed mAbs, adalimumab, denosumab, rituximab, etanercept and infliximab were calculated to have the highest relative number of yearly users based on global sales data. Comparing the number of mAb-induced SCLE cases with estimated yearly users, the checkpoint inhibitors pembrolizumab and nivolumab showed strikingly high rates of SCLE relative to their global use, but ipilimumab did not. Conclusion: We present the first systematic review characterising mAb-induced SCLE with respect to triggers, clinical signs, laboratory findings, prognosis and treatment approaches. We identify elevated rates associated with the use of checkpoint inhibitors and anti-TNFɑ agents

Extent and prevalence of post-exercise and nocturnal hypoglycemia following peri-exercise bolus insulin adjustments in individuals with type 1 diabetes

To detail the extent and prevalence of post-exercise and nocturnal hypoglycemia following peri-exercise bolus insulin dose adjustments in individuals with type 1 diabetes (T1D) using multiple daily injections of insulins aspart (IAsp) and degludec (IDeg)