Climate change and future pollen allergy in Europe

Background: Globally pollen allergy is a major public health problem, but a fundamental unknown is the likely impact of climate change. To our knowledge, this is the first study to quantify the consequences of climate change upon pollen allergy in humans. Objectives: To produce quantitative estimates of the potential impact of climate change upon pollen allergy in humans, focusing upon common ragweed (Ambrosia artemisiifolia) in Europe. Methods: A process-based model estimated the change in ragweed’s range under climate change. A second model simulated current and future ragweed pollen levels. These were translated into health burdens using a dose-response curve generated from a systematic review and current and future population data. Models considered two different suites of regional climate/pollen models, two greenhouse gas emissions scenarios (RCP4.5 and 8.5), and three different plant invasion scenarios. Results: Our primary estimates indicate that sensitization to ragweed will more than double in Europe, from 33 to 77 million people, by 2041-2060. According to our projections, while sensitization will increase in countries with an existing ragweed problem (e.g. Hungary, the Balkans), the greatest proportional increases will occur where sensitization is uncommon (e.g. Germany, Poland, France). Higher pollen concentrations and a longer pollen season may also increase the severity of symptoms. Our model projections are driven predominantly by changes in climate (66%), but also are influenced by current trends in the spread of this invasive plant species. Assumptions about the rate at which ragweed spreads throughout Europe have a large influence upon the results. Conclusions: Our quantitative estimates indicate that ragweed pollen allergy will become a common health problem across Europe, expanding into areas where it is currently uncommon. Control of ragweed spread may be an important adaptation strategy in response to climate change

The great melting pot. Common sole population connectivity assessed by otolith and water fingerprints

Quantifying the scale and importance of individual dispersion between populations and life stages is a key challenge in marine ecology. The common sole (Solea solea), an important commercial flatfish in the North Sea, Atlantic Ocean and the Mediterranean Sea, has a marine pelagic larval stage, a benthic juvenile stage in coastal nurseries (lagoons, estuaries or shallow marine areas) and a benthic adult stage in deeper marine waters on the continental shelf. To date, the ecological connectivity among these life stages has been little assessed in the Mediterranean. Here, such an assessment is provided for the first time for the Gulf of Lions, NW Mediterranean, based on a dataset on otolith microchemistry and stable isotopic composition as indicators of the water masses inhabited by individual fish. Specifically, otolith Ba/Ca and Sr/Ca profiles, and delta C-13 and delta O-18 values of adults collected in four areas of the Gulf of Lions were compared with those of young-of-the-year collected in different coastal nurseries. Results showed that a high proportion of adults (>46%) were influenced by river inputs during their larval stage. Furthermore Sr/Ca ratios and the otolith length at one year of age revealed that most adults (similar to 70%) spent their juvenile stage in nurseries with high salinity, whereas the remainder used brackish environments. In total, data were consistent with the use of six nursery types, three with high salinity (marine areas and two types of highly saline lagoons) and three brackish (coastal areas near river mouths, and two types of brackish environments), all of which contributed to the replenishment of adult populations. These finding implicated panmixia in sole population in the Gulf of Lions and claimed for a habitat integrated management of fisherie

Water Availability Is the Main Climate Driver of Neotropical Tree Growth

• Climate models for the coming century predict rainfall reduction in the Amazonian region, including change in water availability for tropical rainforests. Here, we test the extent to which climate variables related to water regime, temperature and irradiance shape the growth trajectories of neotropical trees. • We developed a diameter growth model explicitly designed to work with asynchronous climate and growth data. Growth trajectories of 205 individual trees from 54 neotropical species censused every 2 months over a 4-year period were used to rank 9 climate variables and find the best predictive model. • About 9% of the individual variation in tree growth was imputable to the seasonal variation of climate. Relative extractable water was the main predictor and alone explained more than 60% of the climate effect on tree growth, i.e. 5.4% of the individual variation in tree growth. Furthermore, the global annual tree growth was more dependent on the diameter increment at the onset of the rain season than on the duration of dry season. • The best predictive model included 3 climate variables: relative extractable water, minimum temperature and irradiance. The root mean squared error of prediction (0.035 mm.d–1) was slightly above the mean value of the growth (0.026 mm.d–1). • Amongst climate variables, we highlight the predominant role of water availability in determining seasonal variation in tree growth of neotropical forest trees and the need to include these relationships in forest simulators to test, in silico, the impact of different climate scenarios on the future dynamics of the rainforest

Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls

Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group

Funder: U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)Funder: National Center for Research Resources under award number 1 C06 RR12463-01, VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the DOD Prostate Cancer Idea Development Award (W81XWH-15-1-0558), the DOD Lung Cancer Investigator-Initiated Translational Research Award (W81XWH-18-1-0440), the DOD Peer Reviewed Cancer Research Program (W81XWH-16-1-0329), the Ohio Third Frontier Technology Validation Fund, the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering and the Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University.Funder: Susan G Komen Foundation (CCR CCR18547966) and a Young Investigator Grant from the Breast Cancer Alliance.Funder: The Canadian Cancer SocietyFunder: Breast Cancer Research Foundation (BCRF), Grant No. 17-194Abstract: Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Funder: Breast Cancer Research Foundation (BCRF); doi: https://doi.org/10.13039/100001006Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

https://deepblue.lib.umich.edu/bitstream/2027.42/138963/1/12987_2017_Article_71.pd