New land-use-change emissions indicate a declining CO₂ airborne fraction

About half of the anthropogenic CO2 emissions remain in the atmosphere and half are taken up by the land and ocean1. If the carbon uptake by land and ocean sinks becomes less efficient, for example, owing to warming oceans2 or thawing permafrost3, a larger fraction of anthropogenic emissions will remain in the atmosphere, accelerating climate change. Changes in the efficiency of the carbon sinks can be estimated indirectly by analysing trends in the airborne fraction, that is, the ratio between the atmospheric growth rate and anthropogenic emissions of CO2 (refs. 4–10). However, current studies yield conflicting results about trends in the airborne fraction, with emissions related to land use and land cover change (LULCC) contributing the largest source of uncertainty7,11,12. Here we construct a LULCC emissions dataset using visibility data in key deforestation zones. These visibility observations are a proxy for fire emissions13,14, which are — in turn — related to LULCC15,16. Although indirect, this provides a long-term consistent dataset of LULCC emissions, showing that tropical deforestation emissions increased substantially (0.16 Pg C decade−1) since the start of CO2 concentration measurements in 1958. So far, these emissions were thought to be relatively stable, leading to an increasing airborne fraction4,5. Our results, however, indicate that the CO2 airborne fraction has decreased by 0.014 ± 0.010 decade−1 since 1959. This suggests that the combined land–ocean sink has been able to grow at least as fast as anthropogenic emissions

Immunologic responses to xenogeneic tyrosinase DNA vaccine administered by electroporation in patients with malignant melanoma

BACKGROUND: Prior studies show that intramuscular injection and particle-mediated epidermal delivery of xenogeneic melanosomal antigens (tyrosinase or Tyr, gp100) induce CD8(+) T cell responses to the syngeneic protein. To further define the optimal vaccination strategy, we conducted a phase I study of in vivo electroporation (EP) of a murine Tyr DNA vaccine (pINGmuTyr) in malignant melanoma patients. METHODS: Human leukocyte antigen (HLA)-A1, A2, A24 or B35 stage IIb-IV melanoma patients received up to five doses of the mouse tyrosinase DNA vaccine by EP every three weeks at dose levels of 0.2 mg, 0.5 mg, or 1.5 mg per injection. Peripheral blood mononuclear cells (PBMC) were collected, cultured with a peptide pool containing eight HLA class I-restricted Tyr-specific T-cell epitopes, and analyzed by HLA-A*0101-restricted tetramers and intracellular cytokine staining (ICS). RESULTS: Twenty-four patients received ≥1 dose of the pINGmuTyr vaccine; PBMCs from 21 patients who completed all five doses were available for Tyr immune assays. The only common toxicity was grade 1 injection site reaction. Six of 15 patients (40%) in the 1.5 mg dose cohort developed Tyr-reactive CD8(+) T cell responses following stimulation, defined as a ≥3 standard deviation increase in baseline reactivity by tetramer or ICS assays. No Tyr-reactive CD8(+) T cell response was detected in the 0.2 mg and 0.5 mg dose cohort patients. Epitope spreading of CD8(+) T cell response to NY-ESO-1 was observed in one patient with vitiligo. One patient subsequently received ipilimumab and developed an enhanced Tyr-reactive response with polyfunctional cytokine profile. After a median follow-up of 40.9 months, median survival has not been reached. CONCLUSIONS: A regimen of five immunizations with pINGmuTyr administered by EP was found to be safe and resulted in Tyr-reactive immune responses in six of 15 patients at 1.5 mg dose cohort. TRIAL REGISTRATION: ClinicalTrials.gov NCT0047113

Cosmology From Random Multifield Potentials

We consider the statistical properties of vacua and inflationary trajectories associated with a random multifield potential. Our underlying motivation is the string landscape, but our calculations apply to general potentials. Using random matrix theory, we analyze the Hessian matrices associated with the extrema of this potential. These potentials generically have a vast number of extrema. If the cross-couplings (off-diagonal terms) are of the same order as the self-couplings (diagonal terms) we show that essentially all extrema are saddles, and the number of minima is effectively zero. Avoiding this requires the same separation of scales needed to ensure that Newton's constant is stable against radiative corrections in a string landscape. Using the central limit theorem we find that even if the number of extrema is enormous, the typical distance between extrema is still substantial -- with challenging implications for inflationary models that depend on the existence of a complicated path inside the landscape.Comment: revtex, 3 figures, 10 pages v2 refs adde

Mapping and monitoring carbon stocks with satellite observations: a comparison of methods

Mapping and monitoring carbon stocks in forested regions of the world, particularly the tropics, has attracted a great deal of attention in recent years as deforestation and forest degradation account for up to 30% of anthropogenic carbon emissions, and are now included in climate change negotiations. We review the potential for satellites to measure carbon stocks, specifically aboveground biomass (AGB), and provide an overview of a range of approaches that have been developed and used to map AGB across a diverse set of conditions and geographic areas. We provide a summary of types of remote sensing measurements relevant to mapping AGB, and assess the relative merits and limitations of each. We then provide an overview of traditional techniques of mapping AGB based on ascribing field measurements to vegetation or land cover type classes, and describe the merits and limitations of those relative to recent data mining algorithms used in the context of an approach based on direct utilization of remote sensing measurements, whether optical or lidar reflectance, or radar backscatter. We conclude that while satellite remote sensing has often been discounted as inadequate for the task, attempts to map AGB without satellite imagery are insufficient. Moreover, the direct remote sensing approach provided more coherent maps of AGB relative to traditional approaches. We demonstrate this with a case study focused on continental Africa and discuss the work in the context of reducing uncertainty for carbon monitoring and markets

International Trade and Investment Sanctions

The purpose of this paper is to clarify the theory of international economic sanctions and to provide estimates of the short-run economic impact on South Africa of externally imposed reductions of the imports and capital flows into that country. A macroeconomic picture of South Africa's "dependence" is drawn, and the economy's vulnerability in the short run is seen to be in its capacity to import, not in exports or capital flows. Trade and capital sanctions most clearly damage South Afnca's growth potential; the short-run impact is harder to quantify. A static linear programming model of the South African economy is constructed in an attempt at this quantification. This model estimates that small sanctions would have small impact—i.e., if imports were reduced by less than one-fourth, GDP would be cut by only about one half as large a percentage as imports. Larger import reductions cause greater damage. If imports were to be cut in half, not only would GDP be seriously reduced but massive unemployment and relocation of white labor would occur.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68182/2/10.1177_002200277902300401.pd

The largest deep-ocean silicic volcanic eruption of the past century

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Science Advances 4 (2018): e1701121, doi:10.1126/sciadv.1701121.The 2012 submarine eruption of Havre volcano in the Kermadec arc, New Zealand, is the largest deep-ocean eruption in history and one of very few recorded submarine eruptions involving rhyolite magma. It was recognized from a gigantic 400-km2 pumice raft seen in satellite imagery, but the complexity of this event was concealed beneath the sea surface. Mapping, observations, and sampling by submersibles have provided an exceptionally high fidelity record of the seafloor products, which included lava sourced from 14 vents at water depths of 900 to 1220 m, and fragmental deposits including giant pumice clasts up to 9 m in diameter. Most (>75%) of the total erupted volume was partitioned into the pumice raft and transported far from the volcano. The geological record on submarine volcanic edifices in volcanic arcs does not faithfully archive eruption size or magma production.This research was funded by Australian Research Council Postdoctoral fellowships (DP110102196 and DE150101190 to R. Carey), a short-term postdoctoral fellowship grant from the Japan Society for the Promotion of Science (to R. Carey), National Science Foundation grants (OCE1357443 to B.H., OCE1357216 to S.A.S., and EAR1447559 to J.D.L.W.), and a New Zealand Marsden grant (U001616 to J.D.L.W.). J.D.L.W. and A.M. were supported by a research grant and PhD scholarship from the University of Otago. R.W. was supported by NIWA grant COPR1802. J.D.L.W. and F.C.-T. were supported by GNS Science grants CSA-GHZ and CSA-EEZ. M.J. was supported by the U.S. Department of Defense (DoD) through the National Defense Science and Engineering Graduate Fellowship (NDSEG) Program

Efficacy and pharmacokinetic/pharmacodynamic evaluation of the Aurora kinase A inhibitor MLN8237 against preclinical models of pediatric cancer

To gain a greater understanding of the potential of the Aurora kinase A inhibitor MLN8237 in the treatment of pediatric malignancies. The activity of MLN8237 was evaluated against 28 neuroblastoma and Ewing sarcoma cell lines, and its in vivo efficacy was studied over a range of doses against 12 pediatric tumor xenograft models. Pharmacokinetic, pharmacodynamic, and genomic studies were undertaken. In vitro neuroblastoma cell lines were generally more sensitive to MLN8237 than Ewing sarcoma lines. MLN8237 demonstrated significant activity in vivo against solid tumor models at the maximum tolerated dose (MTD); however, only 2 of 6 neuroblastoma models had objective responses at 0.25MTD. In contrast, MLN8237 induced objective responses at its MTD and at 0.5MTD in three ALL models and in two out of three at 0.25MTD. Pharmacokinetic studies at 0.5MTD demonstrated a T (max) of 0.5 h, C (max) of 24.8 mu M, AUC((0-24)) of 60.3 mu M h, and 12 h trough level of 1.2 mu M. Mitotic indices increased 6-12 h after MLN8237 administration. AURKA copy number variation was frequent in xenografts, and expression was highly correlated with copy number. Objective responses were more frequent in tumors with decreased AURKA copy number (5/8) compared to those with increased gene copy number (2/14). This report confirms the significant activity against both solid tumor and ALL xenografts at the MTD, with a steep dose response. These data support clinical development of MLN8237 in childhood cancer. Because of the steep dose-response relationship, such studies should target achieving trough levels of 1 mu M or higher for sustained periods of treatment

Natural climate solutions for the United States

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Science Advances 4 (2018): eaat1869, doi:10.1126/sciadv.aat1869.Limiting climate warming to <2°C requires increased mitigation efforts, including land stewardship, whose potential in the United States is poorly understood. We quantified the potential of natural climate solutions (NCS)—21 conservation, restoration, and improved land management interventions on natural and agricultural lands—to increase carbon storage and avoid greenhouse gas emissions in the United States. We found a maximum potential of 1.2 (0.9 to 1.6) Pg CO2e year−1, the equivalent of 21% of current net annual emissions of the United States. At current carbon market prices (USD 10 per Mg CO2e), 299 Tg CO2e year−1 could be achieved. NCS would also provide air and water filtration, flood control, soil health, wildlife habitat, and climate resilience benefits.This study was made possible by funding from the Doris Duke Charitable Foundation. C.A.W. and H.G. acknowledge financial support from NASA’s Carbon Monitoring System program (NNH14ZDA001N-CMS) under award NNX14AR39G. S.D.B. acknowledges support from the DOE’s Office of Biological and Environmental Research Program under the award DE-SC0014416. J.W.F. acknowledges financial support from the Florida Coastal Everglades Long-Term Ecological Research program under National Science Foundation grant no. DEB-1237517

Methodology

© The Author(s) 2019. A detailed overview of the methodologies used to develop the 2.0 °C and 1.5 °C scenario presented in this book. Starting with the overall modelling approach, the interaction of seven different models is explained which are used to calculate and developed detailed scenarios for greenhouse gas emission and energy pathways to stay within a 2.0 °C and 1.5 °C global warming limit. The following models are presented: For the non-energy GHG emission pathways, the Generalized Equal Quantile Walk (GQW)method, the land-based sequestration design method and the Carbon cycle and climate (MAGICC) model. For the energy pathways, a renewable energy resources assessment for space constrained environments ([R]E-SPACE, the transport scenario model (TRAEM), the Energy System Model (EM) and the power system model [R]E 24/7. The methodologies of an employment analysis model, and a metal resource assessment tool are outlined. These models have been used to examine the analysis of the energy scenario results

The Bangladesh Risk of Acute Vascular Events (BRAVE) Study: objectives and design.

During recent decades, Bangladesh has experienced a rapid epidemiological transition from communicable to non-communicable diseases. Coronary heart disease (CHD), with myocardial infarction (MI) as its main manifestation, is a major cause of death in the country. However, there is limited reliable evidence about its determinants in this population. The Bangladesh Risk of Acute Vascular Events (BRAVE) study is an epidemiological bioresource established to examine environmental, genetic, lifestyle and biochemical determinants of CHD among the Bangladeshi population. By early 2015, the ongoing BRAVE study had recruited over 5000 confirmed first-ever MI cases, and over 5000 controls "frequency-matched" by age and sex. For each participant, information has been recorded on demographic factors, lifestyle, socioeconomic, clinical, and anthropometric characteristics. A 12-lead electrocardiogram has been recorded. Biological samples have been collected and stored, including extracted DNA, plasma, serum and whole blood. Additionally, for the 3000 cases and 3000 controls initially recruited, genotyping has been done using the CardioMetabochip+ and the Exome+ arrays. The mean age (standard deviation) of MI cases is 53 (10) years, with 88 % of cases being male and 46 % aged 50 years or younger. The median interval between reported onset of symptoms and hospital admission is 5 h. Initial analyses indicate that Bangladeshis are genetically distinct from major non-South Asian ethnicities, as well as distinct from other South Asian ethnicities. The BRAVE study is well-placed to serve as a powerful resource to investigate current and future hypotheses relating to environmental, biochemical and genetic causes of CHD in an important but under-studied South Asian population.The Gates Cambridge Trust has supported Dr Chowdhury. Epidemiological fieldwork in BRAVE has been supported by grants to investigators at the Cardiovascular Epidemiology Unit, University of Cambridge. The Cardiovascular Epidemiology Unit is underpinned by programme grants from the British Heart Foundation (RG/13/13/30194), the UK Medical Research Council (MR/L003120/1), and the UK National Institute of Health Research Cambridge Biomedical Research Centre. BRAVE has received support for genetic assays from the European Research Council (ERC-2010-AdG-20100317), European Commission Framework 7 (Grant Agreement number: 279233), and the Cambridge British Heart Foundation Centre for Excellence in Cardiovascular Science; We would like to acknowledge the contributions of the following individuals: Cardiology Research Group in Bangladesh Mohammad Afzalur Rahman, Mohammad Abdul Kader Akanda, M Atahar Ali, Mir Jamal Uddin, SM Siddiqur Rahman, Amal Kumar Choudhury, Md. Mamunur Rashid, Nazir Ahmed Chowdhury, Mohammad Abdullahel Baqui, Kajal Kumar Karmoker, Mohammad Golam Azam; Setting up/implementation of fieldwork in Bangladesh Abbas Bhuiya, Susmita Chowdhury, Kamrun Nahar, Neelima Das, Proshon Roy, Sumona Ferdous, Taposh Kumar Biswas, Abu Sadat Mohammad Sayed Sharif, Ranjit Shingha, Rose Jinnath Tomas, Babulal Parshei, Mabubur Rahman, Mohammad Emon Hossain, Akhirunnesa Mily, AK Mottashir Ahmed, Sati Chowdhury, Sushila Roy, Dipak Kanti Chowdhury, Swapan Kumar Roy; Epidemiological/statistical support in Cambridge Stephen Kaptoge, Simon Thompson, Angela Wood, Narinder Bansal, Anna Ramond, Clare Oliver-Williams, Marinka Steur, Linda O’Keeffe, Eleni Sofianopoulou, Setor Kunutsor, Donal Gorman, Oscar H Franco, Malcolm Legget, Pinal Patel, Marc Suhrcke, Sylvaine Bruggraber, Jonathan Powell; Data management Matthew Walker, Steve Ellis, Shawkat Jahangir, Habibur Rahman, Rifat Hasan Shammi, Shafqat Ullah, Mohammad Abdul Matin and Administration Beth Collins, Hannah Lombardi, Binder Kaur, Rachel Henry, Marilena Papanikolaou, Robert Smith, Abdul Wazed, Robert Williams, Julie Jenkins, Keith Hoddy.This is the final published version of the article. It was originally published in the European Journal of Epidemiology (Chowdhury R, et al., European Journal of Epidemiology, 2015, doi:10.1007/s10654-015-0037-2). The final version is available at http://dx.doi.org/10.1007/s10654-015-0037-