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ProZES: the methodology and software tool for assessment of assigned share of radiation in probability of cancer occurrence

ProZES is a software tool for estimating the probability that a given cancer was caused by preceding exposure to ionising radiation. ProZES calculates this probability, the assigned share, for solid cancers and hematopoietic malignant diseases, in cases of exposures to low-LET radiation, and for lung cancer in cases of exposure to radon. User-specified inputs include birth year, sex, type of diagnosed cancer, age at diagnosis, radiation exposure history and characteristics, and smoking behaviour for lung cancer. Cancer risk models are an essential part of ProZES. Linking disease and exposure to radiation involves several methodological aspects, and assessment of uncertainties received particular attention. ProZES systematically uses the principle of multi-model inference. Models of radiation risk were either newly developed or critically re-evaluated for ProZES, including dedicated models for frequent types of cancer and, for less common diseases, models for groups of functionally similar cancer sites. The low-LET models originate mostly from the study of atomic bomb survivors in Hiroshima and Nagasaki. Risks predicted by these models are adjusted to be applicable to the population of Germany and to different time periods. Adjustment factors for low dose rates and for a reduced risk during the minimum latency time between exposure and cancer are also applied. The development of the methodology and software was initiated and supported by the German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU) taking up advice by the German Commission on Radiological Protection (SSK, Strahlenschutzkommission). These provide the scientific basis to support decision making on compensation claims regarding malignancies following occupational exposure to radiation in Germany.

97 MATHEMATICS AND COMPUTING↗

Multidimensional perspectives of geo-epidemiology: from interdisciplinary learning and research to cost–benefit oriented decision-making

Research typically promotes two types of outcomes (inventions and discoveries), which induce a virtuous cycle: something suspected or desired (not previously demonstrated) may become known or feasible once a new tool or procedure is invented and, later, the use of this invention may discover new knowledge. Research also promotes the opposite sequence—from new knowledge to new inventions. This bidirectional process is observed in geo-referenced epidemiology—a field that relates to but may also differ from spatial epidemiology. Geo-epidemiology encompasses several theories and technologies that promote inter/transdisciplinary knowledge integration, education, and research in population health. Based on visual examples derived from geo-referenced studies on epidemics and epizootics, this report demonstrates that this field may extract more (geographically related) information than simple spatial analyses, which then supports more effective and/or less costly interventions. Actual (not simulated) bio-geo-temporal interactions (never captured before the emergence of technologies that analyze geo-referenced data, such as geographical information systems) can now address research questions that relate to several fields, such as Network Theory. Thus, a new opportunity arises before us, which exceeds research: it also demands knowledge integration across disciplines as well as novel educational programs which, to be biomedically and socially justified, should demonstrate cost-effectiveness. Grounded on many bio-temporal-georeferenced examples, this report reviews the literature that supports this hypothesis: novel educational programs that focus on geo-referenced epidemic data may help generate cost-effective policies that prevent or control disease dissemination.

59 BASIC BIOLOGICAL SCIENCES↗

Are Medications Involved in Vision and Intracrancial Pressure Changes Seen in Spaceflight?

The Food and Drug Association Adverse Event Reports (FDA AER) from 2009-2011 were used to create a database from millions of known and suspected medication-related adverse events among the general public. Vision changes, sometimes associated with intracranial pressure changes (VIIP), have been noted in some long duration crewmembers. Changes in vision and blood pressure (which can subsequently affect intracranial pressure) are fairly common side effects of medications. The purpose of this study was to explore the possibility of medication involvement in crew VIIP symptoms. Reports of suspected medication-related adverse events may be filed with the Food and Drug Administration (FDA) by medical professionals or consumers. Quarterly compilations of these reports are available for public download. Adverse Event Reporting System (AERS) reports from 1/1/2009- 6/30/2012 were downloaded and compiled into a searchable database for this study. Reports involving individuals under the age of 18 and older than 65 were excluded from this analysis. Case reports involving chronic diseases such as cancer, diabetes, multiple sclerosis and other serious conditions were also excluded. A scan of the medical literature for medication-related VIIP-like adverse events was used to create a list of suspect medications. These medications, as well as certain medications used frequently by ISS crew, were used to query the database. Queries for use of suspected medications were run, and the nature of the symptoms reported in those cases were tabulated. Symptoms searched in the FDA AERS were chosen to include the typical symptoms noted in crewmembers with VIIP. Vision symptoms searched were: visual acuity reduced, visual impairment, and vitreous floaters. Pressure changes included: abnormal sensation in eye, intracranial pressure increased, intraocular pressure increased, optic neuritis, optic neuropathy, and papilloedema. Limited demographic information is included with the FDA AERS; relevant data were also sorted by age and sex from each report. RESULTS Steroid-containing oral contraceptives had the highest number of reports associated with vision (n=166) and pressure symptoms (n=54). Corticosteroid-containing medications were also high; prednisone, for example, had 137 reports of vision issues and 79 of pressure issues. Pain relievers were also a medication class with vision and pressure-related adverse events reported. Common over-the-counter medications such as acetaminophen, aspirin and ibuprofen each had multiple reports for both vision and pressure symptoms. Antimicrobial medications ciprofloxacin and diflucan were also associated with a number of vision and pressure-related AERS. Unexpectedly, pseudoephedrine and promethazine were mentioned in fewer than 20 reports each over the 3.5 years of data examined. The FDA AERS represents a wealth of data, but there are several limitations to its use. The data are entered by the public or medical professionals, but are not checked for accuracy or completeness and may even be entered multiple times. The causal relationship between a particular adverse event and a particular medication is not tested. The cases represent a broad spectrum of demographics, occupations, and health histories, and thus do not model the astronaut population well. There is no information on the frequency of use of a medication for comparison purposes; it is not possible to assign a rate for any particular adverse event. Nonetheless, there are compelling trends. Use of corticosteroid-containing medications, pain relievers (even over-the-counter), and oral contraceptives were associated with higher numbers of vision- or intracranial pressure-related adverse events. In general, there were more vision problems than pressure problems reported. Certain medications that were once suspected of playing a role in the crew VIIP syndrome, namely pseudoephedrine and promethazine, were found to have extremely low numbers of VIIP-like AERS in the FDA data. However, crew use of corticosteroid-containing medications and pain relievers may warrant additional investigation

Faust, K. M.↗

Observation of Hydrological Processes Using Remote Sensing: Volume 2: The Science of Hydrology - Chapter 2.14

Improving water management can make a significant contribution to achieving most of the Millennium Development Goals established by the UN General Assembly in 2000, especially those related to poverty, hunger, and major diseases. The World Summit on Sustainable Development (WSSD) in 2002 recognized this need. Water and sanitation in particular received great attention from the Summit. The Johannesburg Plan of Implementation recommended to improve water resources management and scientific understanding of the water cycle through joint cooperation and research. For this purpose, it is recommended to promote knowledge sharing, provide capacity building, and facilitate the transfer of technology including remote-sensing (RS) and satellite technologies, especially to developing countries and countries with economies in transition, and to support these countries in their efforts to monitor and assess the quantity and quality of water resources, for example, by establishing and/or further developing national monitoring networks and water resources databases and by developing relevant national indicators. The Johannesburg Plan also adopted integrated water resources management as the overarching concept in addressing and solving water-related issues. As a result of the commitments made in the Johannesburg Plan of Implementation, several global and regional initiatives have emerged. Current international initiatives such as the Global Monitoring for Environment and Security (GMES) program of the European Commission and the European Space Agency (ESA), and the Global Earth Observation System of Systems (GEOSS) 10-Year Implementation Plan, have all identified Earth observation (EO) of the water cycle as the key in helping to solve the world s water problems. The availability of spatial information on water quantity and quality will also enable closure of the water budget at river basin and continental scales to the point where effective water management is essential (e.g., as requested by the European Union s Water Framework Directive (WFD), as well as national policies). Geo-information science and EO are vital in achieving a better understanding of the water cycle and better monitoring, analysis, prediction, and management of the world s water resources. The major components of the water cycle of the Earth system and their possible observations are presented. Such observations are essential to understand the global water cycle and its variability, both spatially and temporally, and can only be achieved consistently by means of EOs. Additionally, such observations are essential to advance our understanding of coupling between the terrestrial, atmospheric, and oceanic branches of the water cycle, and how this coupling may influence climate variability and predictability. Water resources management directly interferes with the natural water cycle in the forms of building dams, reservoirs, water transfer systems, and irrigation systems that divert and redistribute part of the water storages and fluxes on land. The water cycle is mainly driven and coupled to the energy cycle in terms of phase changes of water (changes among liquid, water vapor, and solid phases) and transport of water by winds in addition to gravity and diffusion processes. The water-cycle components can be observed with in situ sensors as well as airborne and satellite sensors in terms of radiative quantities. Processing and conversion of these radiative signals are necessary to retrieve the water-cycle components.

Wilder, Peter↗

PNNL DataHub Project: Omics Lethal Human Viruses Project Profiling of the Host Interferon-Stimulated Response to Virus Infection, Processed Experimental Dataset Catalog

Human Interferon (IFN) alpha, beta, and gamma participate in the body's natural immune response to lethal virus infection and disease.The NIAID Modeling Host Responses to Understand Severe Human Virus Infections Research Program project (2013 - 2018) aimed to develop an improved comprehensive understanding of the host response to a suite of viruses causing lethal infections leveraging a systems biology approach. The NIAID Modeling Host Responses to Understand Severe Human Virus Infections Research Program project (2013-2018) aimed to develop an improved comprehensive understanding of the host response to a suite of viruses causing lethal infections leveraging a systems biology approach. Herein, PNNL sub-projects provide a never before released comprehensive infectious disease collection of primary and secondary transformation multi-Omics data profiling a series of priority pathogen primary experimental studies for enhanced open-access to viral Omics datasets and project lifecycle metadata. Secondary host-associated viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Transcriptomics (T) dataset downloads each have a direct relationship to a primary sample submission corresponding to a specific Human Interferon (IFN), interferon alpha (IFNα), interferon beta (IFNβ), and/or interferon gamma (IFNγ) stimulated response to an experimental virus infection treatment study. Host sample types include cerebellum ["CB", BTO:0000232], cortical neurons ["CN", BTO:0004102], cortex ["CT", BTO:0000233], dendritic cells ["DC", BTO:0002042], granule cell neurons ["GCN", BTO:0003393], lymph node ["LN", BTO:0000784], and serum ["SE", BTO:0001239] from mouse (Mus musculus) tissue collections.

59 BASIC BIOLOGICAL SCIENCES↗

PNNL DataHub Project: Omics Lethal Human Viruses Project Profiling of the Host Response to West Nile Virus Infection, Processed Experimental Dataset Catalog

West Nile virus (WNV) is classified as a Category B priority pathogen (mosquito-borne Flavivirus) by the National Institute of Allergy and Infectious Diseases (NIAID), and are known to cause severe infections in humans where lethal host-associated mechanisms are not clearly defined. The NIAID Modeling Host Responses to Understand Severe Human Virus Infections Research Program project (2013 - 2018) aimed to develop an improved comprehensive understanding of the host response to a suite of viruses causing lethal infections leveraging a systems biology approach. The NIAID Modeling Host Responses to Understand Severe Human Virus Infections Research Program project (2013-2018) aimed to develop an improved comprehensive understanding of the host response to a suite of viruses causing lethal infections leveraging a systems biology approach. Herein, PNNL sub-projects provide a never before released comprehensive infectious disease collection of primary and secondary transformation multi-Omics data profiling a series of priority pathogen primary experimental studies for enhanced open-access to viral Omics datasets and project lifecycle metadata. Secondary host-pathogen viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Leveraging unique high-resolution Omics capabilities for proteomics (P), metabolomics (M), lipidomics (L), and transcriptomics (T) dataset downloads each have a direct relationship to a primary sample submission corresponding a specific West Nile virus [NCBITAXON:11082] (WNV-NY99 382) experimental infection study. Host sample types include cerebellum ["CB", BTO:0000232], cortical neurons ["CN", BTO:0004102], cortex ["CT", BTO:0000233], dendritic cells ["DC", BTO:0002042], granule cell neurons ["GCN", BTO:0003393], lymph node ["LN", BTO:0000784], and serum ["SE", BTO:0001239] from mouse (Mus musculus) tissue collections.

59 BASIC BIOLOGICAL SCIENCES↗

PNNL DataHub Project: Omics Lethal Human Viruses Project Profiling of the Host Response to Ebola Virus Infection, Processed Experimental Dataset Catalog

Ebola virus (EBOV) is high risk biological agent, classified as a Category A priority pathogen (Flaviviridae) by the National Institute of Allergy and Infectious Diseases (NIAID), known to cause hemorrhagic fever with high mortality rates in humans. Lethal host-pathogen invasion mechanisms and the cellular intricacies behind these fatal infections still remain unclear. The NIAID Modeling Host Responses to Understand Severe Human Virus Infections Research Program project (2013-2018) aimed to develop an improved comprehensive understanding of the host response to a suite of viruses causing lethal infections leveraging a systems biology approach. Herein, PNNL sub-projects provide a never before released comprehensive infectious disease collection of primary and secondary transformation multi-Omics data profiling a series of priority pathogen primary experimental studies for enhanced open-access to viral Omics datasets and project lifecycle metadata. Secondary host-pathogen viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Leveraging unique high-resolution Omics capabilities for proteomics (P), metabolomics (M), lipidomics (L), and transcriptomics (T) dataset downloads each have a direct relationship to a primary sample submission corresponding to a specific Ebola virus [NCBITAXON:186536] (Zaire/Makona or Zaire/Mayinga) experimental infection study. Human host samples types include peripheral blood mononuclear cells isolated from blood plasma ["PBMC", BTO:0001025], human hepatoma carcinoma cells ["HUH", BTO:0001950], human umbilical vein endothelial cells ["HUVEC", BTO:0001949], immortalized human hepatocyte cells ["IHH", BTO:0006147], and human histiocytic lymphoma cells ["U937", BTO:0001412].

59 BASIC BIOLOGICAL SCIENCES↗

Omics Lethal Human Viruses Project Profiling of the Host Response to MERS-CoV Infection, Processed Experimental Dataset Catalog

Middle East Respiratory Syndrome coronavirus (MERS-CoV) is classified as a Category C priority pathogen (Coronaviridae) by the National Institute of Allergy and Infectious Diseases (NIAID), and is known to cause severe respiratory disease with high mortality rates in humans. Lethal host-pathogen invasion mechanisms and the cellular intricacies behind these fatal infections still remain unclear. The NIAID Modeling Host Responses to Understand Severe Human Virus Infections Research Program project (2013-2018) aimed to develop an improved comprehensive understanding of the host response to a suite of viruses causing lethal infections leveraging a systems biology approach. Herein, PNNL sub-projects provide a never before released comprehensive infectious disease collection of primary and secondary transformation multi-Omics data profiling a series of priority pathogen primary experimental studies for enhanced open-access to viral Omics datasets and project lifecycle metadata. Secondary host-pathogen viral dataset downloads contain one or more statistically processed (normalization data transformation) quantitative dataset collections resulting in qualitative expression analyses of primary host-pathogen experimental study designs. Leveraging unique high-resolution Omics capabilities for proteomics (P), metabolomics (M), lipidomics (L), and transcriptomics (T) dataset downloads each have a direct relationship to a primary sample submission corresponding to a specific MERS-CoV [NCBITAXON:1335626] experimental infection study. Host sample types include human lung adenocarcinoma cells ["Calu-3", BTO:0002750], human bronchial epithelial cells ["Calu-3 clone 2B4"; BTO:0002022], primary human fibroblasts ["FB"; BTO:0000452], primary human airway epithelial cells ["HAE"; BTO:0005571], human microvascular endothelial cells ["HMVE"; BTO:0003123], and whole mouse lung [BTO:0000763] tissue collections.

59 BASIC BIOLOGICAL SCIENCES↗

Mechanism of karyopherin-β2 binding and nuclear import of ALS variants FUS(P525L) and FUS(R495X)

Mutations in the RNA-binding protein FUS cause familial amyotropic lateral sclerosis (ALS). Several mutations that affect the proline-tyrosine nuclear localization signal (PY-NLS) of FUS cause severe juvenile ALS. FUS also undergoes liquid–liquid phase separation (LLPS) to accumulate in stress granules when cells are stressed. In unstressed cells, wild type FUS resides predominantly in the nucleus as it is imported by the importin Karyopherin-β2 (Kapβ2), which binds with high affinity to the C-terminal PY-NLS of FUS. Here, we analyze the interactions between two ALS-related variants FUS(P525L) and FUS(R495X) with importins, especially Kapβ2, since they are still partially localized to the nucleus despite their defective/missing PY-NLSs. The crystal structure of the Kapβ2·FUS(P525L) PY-NLS complex shows the mutant peptide making fewer contacts at the mutation site, explaining decreased affinity for Kapβ2. Biochemical analysis revealed that the truncated FUS(R495X) protein, although missing the PY-NLS, can still bind Kapβ2 and suppresses LLPS. FUS(R495X) uses its C-terminal tandem arginine-glycine-glycine regions, RGG2 and RGG3, to bind the PY-NLS binding site of Kapβ2 for nuclear localization in cells when arginine methylation is inhibited. These findings suggest the importance of the C-terminal RGG regions in nuclear import and LLPS regulation of ALS variants of FUS that carry defective PY-NLSs.

59 BASIC BIOLOGICAL SCIENCES↗

Noninvasive Diagnosis of Coronary Artery Disease Using 12-Lead High-Frequency Electrocardiograms

A noninvasive, sensitive method of diagnosing certain pathological conditions of the human heart involves computational processing of digitized electrocardiographic (ECG) signals acquired from a patient at all 12 conventional ECG electrode positions. In the processing, attention is focused on low-amplitude, high-frequency components of those portions of the ECG signals known in the art as QRS complexes. The unique contribution of this method lies in the utilization of signal features and combinations of signal features from various combinations of electrode positions, not reported previously, that have been found to be helpful in diagnosing coronary artery disease and such related pathological conditions as myocardial ischemia, myocardial infarction, and congestive heart failure. The electronic hardware and software used to acquire the QRS complexes and perform some preliminary analyses of their high-frequency components were summarized in Real-Time, High-Frequency QRS Electrocardiograph (MSC- 23154), NASA Tech Briefs, Vol. 27, No. 7 (July 2003), pp. 26-28. To recapitulate, signals from standard electrocardiograph electrodes are preamplified, then digitized at a sampling rate of 1,000 Hz, then analyzed by the software that detects R waves and QRS complexes and analyzes them from several perspectives. The software includes provisions for averaging signals over multiple beats and for special-purpose nonrecursive digital filters with specific low- and high-frequency cutoffs. These filters, applied to the averaged signal, effect a band-pass operation in the frequency range from 150 to 250 Hz. The output of the bandpass filter is the desired high-frequency QRS signal. Further processing is then performed in real time to obtain the beat-to-beat root mean square (RMS) voltage amplitude of the filtered signal, certain variations of the RMS voltage, and such standard measures as the heart rate and R-R interval at any given time. A key signal feature analyzed in the present method is the presence versus the absence of reduced-amplitude zones (RAZs). In terms that must be simplified for the sake of brevity, an RAZ comprises several cycles of a high-frequency QRS signal during which the amplitude of the high-frequency oscillation in a portion of the signal is abnormally low (see figure). A given signal sample exhibiting an interval of reduced amplitude may or may not be classified as an RAZ, depending on quantitative criteria regarding peaks and troughs within the reduced-amplitude portion of the high-frequency QRS signal. This analysis is performed in all 12 leads in real time.

Schlegel, Todd T.↗

Generating Novel Aroma Phenotypes Using Commercial Wine Samples to Characterize an F1 Population

Due to their disease tolerance and cold hardy nature, interspecific hybrid grapes are widely grown in the Midwestern and Northeastern United States, with additional interest worldwide in the face of increased abiotic and biotic stresses from climate change. However, the aroma profile of these hybrids is unique and generally less popular in comparison with Vitis vinifera grapes. One of the challenges in any phenotyping project is first defining the traits of interest. As wine quality was our ultimate metric of interest, the aroma profile of commercial wines produced from the parents of a breeding population ( Vitis aestivalis derived ‘Norton’ x V. vinifera . ‘Cabernet Sauvignon’) was first assessed for traits of interest. We investigated 11 commercial wines each of Norton, a popular hybrid in Missouri and Cabernet Sauvignon (Cab) for their volatile profiles using the more inclusive metabolomics-based workflow. We then analyzed 21 Norton and 21 Cab grapes from different sites and vintages for the free and bound volatile compounds using HS-SPME-GCMS to validate the differences in wine. The GCMS data was processed using XCMS software to find features that were different between the two cultivars. The two cultivars were found to have differences in their volatile profiles, with 304 features different for wine volatiles, 418 features different for free volatiles, and 302 features different for bound volatiles at 0.05 significance level and with at least a 1.5-fold change between the two cultivars. Those features were used to identify several odor-active compounds in both grapes and wines, including β-damascenone, β-ionone, eugenol, 1,1,6-trimethyl-1,2-dihydronaphthalene (TDN), and methyl salicylate. Some of the identified compounds were higher in Norton than Cab; however, several features were higher in Cab. Using the identified aroma compounds as markers, we phenotyped an F1 population of Norton and Cab. The F1 population was found to be segregating for many aroma compounds with some genotypes demonstrating an even higher concentration of aroma volatiles than either of the parents. Ultimately, using commercially available samples paired with untargeted analysis proved to be an efficient way to determine phenotypes of interest for further analysis and may offer an easy way to choose potential parents with desired traits for breeding.

59 BASIC BIOLOGICAL SCIENCES↗

Future Extreme Heat Scenarios to Enable the Assessment of Climate Impacts on Public Health over the Coterminous U.S.

In the United States, extreme heat is the most deadly weather-related hazard. In the face of a warming climate and urbanization, which contributes to local-scale urban heat islands, it is very likely that extreme heat events (EHEs) will become more common and more severe in the U.S. This research seeks to provide historical and future measures of climate-driven extreme heat events to enable assessments of the impacts of heat on public health over the coterminous U.S. We use atmospheric temperature and humidity information from meteorological reanalysis and from Global Climate Models (GCMs) to provide data on past and future heat events. The focus of research is on providing assessments of the magnitude, frequency and geographic distribution of extreme heat in the U.S. to facilitate public health studies. In our approach, long-term climate change is captured with GCM outputs, and the temporal and spatial characteristics of short-term extremes are represented by the reanalysis data. Two future time horizons for 2040 and 2090 are compared to the recent past period of 1981- 2000. We characterize regional-scale temperature and humidity conditions using GCM outputs for two climate change scenarios (A2 and A1B) defined in the Special Report on Emissions Scenarios (SRES). For each future period, 20 years of multi-model GCM outputs are analyzed to develop a 'heat stress climatology' based on statistics of extreme heat indicators. Differences between the two future and the past period are used to define temperature and humidity changes on a monthly time scale and regional spatial scale. These changes are combined with the historical meteorological data, which is hourly and at a spatial scale (12 km), to create future climate realizations. From these realizations, we compute the daily heat stress measures and related spatially-specific climatological fields, such as the mean annual number of days above certain thresholds of maximum and minimum air temperatures, heat indices and a new heat stress variable developed as part of this research that gives an integrated measure of heat stress (and relief) over the course of a day. Comparisons are made between projected (2040 and 2090) and past (1990) heat stress statistics. Outputs are aggregated to the county level, which is a popular scale of analysis for public health interests. County-level statistics are made available to public health researchers by the Centers for Disease Control and Prevention (CDC) via the Wideranging Online Data for Epidemiologic Research (WONDER) system. This addition of heat stress measures to CDC WONDER allows decision and policy makers to assess the impact of alternative approaches to optimize the public health response to EHEs. Through CDC WONDER, users are able to spatially and temporally query public health and heat-related data sets and create county-level maps and statistical charts of such data across the coterminous U.S

Quattrochi, Dale A.↗

The Effect of Agricultural Growing Season Change on Market Prices in Africa

Local agricultural production is a key element of food security in many agricultural countries in Africa. Climate change and variability is likely to adversely affect these countries, particularly as they affect the ability of smallholder farmers to raise enough food to feed themselves. Seasonality influences farmers' decisions about when to sow and harvest, and ultimately the success or failure of their crops. At a 2009 conference in the United Kingdom hosted by the Institute of Development Studies, Jennings and Magrath (2009) described farmer reports from East Asia, South Asia, Southern Africa, East Africa and Latin America. Farmers indicate significant changes in the timing of rainy seasons and the pattern of rains within seasons, including: More erratic rainfall, coming at unexpected times in and out of season; Extreme storms and unusually intense rainfall are punctuated by longer dry spells within the rainy season; Increasing uncertainty as to the start of rainy seasons in many areas; Short or transitional second rainy seasons are becoming stronger than normal or are disappearing altogether. These farmer perceptions of change are striking in that they are geographically widespread and are remarkably consistent across diverse regions (Jennings and Magrath, 2009). The impact of these changes on farmers with small plots and few resources is large. Farming is becoming riskier because of heat stress, lack of water, pests and diseases that interact with ongoing pressures on natural resources. Lack of predictability in the start and length of the growing season affects the ability of farmers to invest in appropriate fertilizer levels or improved, high yielding varieties. These changes occur at the same time as the demand for food is rising and is projected to continue to rise for the next fifty years (IAASTD, 2008). Long-term data records derived from satellite remote sensing can be used to verify these reports, providing necessary analysis and documentation required to plan effective adaptation strategies. Remote sensing data can also provide some understanding of the spatial extent of these changes and whether they are likely to continue. Given the agricultural nature of most economies on the African continent, agricultural production continues to be a critical determinant of both food security and economic growth (Funk and Brown, 2009). Crop phenological parameters, such as the start and end of the growing season, the total length of the growing season, and the rate of greening and senescence are important for planning crop management, crop diversification, and intensification. The World Food Summit of 1996 defined food security as: "when all people at all times have access to sufficient, safe, nutritious food to maintain a healthy and active life". Food security roughly depends on three factors: 1) availability of food; 2) access to food and 3) appropriate use of food, as well as adequate water and sanitation. The first factor is dependent on growing conditions and weather and climate. In a previous paper we have investigated this factor by evaluating the effect of large scale climate oscillation on land surface phenology (Brown et al., 2010). We found that all areas in Africa are significantly affected by at least one type of large scale climate oscillations and concluded that these somewhat predictable oscillations could perhaps be used to forecast agricultural production. In addition, we have evaluated changes in agricultural land surface phenology over time (Brown et al., 2012). We found that land surface phenology models, which link large-scale vegetation indices with accumulated humidity, could successfully predict agricultural productivity in several countries around the world. In this chapter we are interested in the effect of variability in peak timing of the growing season, or phenology, on the second factor of food security, food access. In this chapter we want to determine if there is a link between market prices and land surface phenology and to determine which markets are vulnerable to land surface phenology changes and variability and which market prices are not correlated.

Prices↗

Linking Excessive Heat with Daily Heat-Related Mortality over the Coterminous United States

In the United States, extreme heat is the most deadly weather-related hazard. In the face of a warming climate and urbanization, which contributes to local-scale urban heat islands, it is very likely that extreme heat events (EHEs) will become more common and more severe in the U.S. This research seeks to provide historical and future measures of climate-driven extreme heat events to enable assessments of the impacts of heat on public health over the coterminous U.S. We use atmospheric temperature and humidity information from meteorological reanalysis and from Global Climate Models (GCMs) to provide data on past and future heat events. The focus of research is on providing assessments of the magnitude, frequency and geographic distribution of extreme heat in the U.S. to facilitate public health studies. In our approach, long-term climate change is captured with GCM outputs, and the temporal and spatial characteristics of short-term extremes are represented by the reanalysis data. Two future time horizons for 2040 and 2090 are compared to the recent past period of 1981- 2000. We characterize regional-scale temperature and humidity conditions using GCM outputs for two climate change scenarios (A2 and A1B) defined in the Special Report on Emissions Scenarios (SRES). For each future period, 20 years of multi-model GCM outputs are analyzed to develop a 'heat stress climatology' based on statistics of extreme heat indicators. Differences between the two future and the past period are used to define temperature and humidity changes on a monthly time scale and regional spatial scale. These changes are combined with the historical meteorological data, which is hourly and at a spatial scale (12 km) much finer than that of GCMs, to create future climate realizations. From these realizations, we compute the daily heat stress measures and related spatially-specific climatological fields, such as the mean annual number of days above certain thresholds of maximum and minimum air temperatures, heat indices, and a new heat stress variable developed as part of this research that gives an integrated measure of heat stress (and relief) over the course of a day. Comparisons are made between projected (2040 and 2090) and past (1990) heat stress statistics. Outputs are aggregated to the county level, which is a popular scale of analysis for public health interests. County-level statistics are made available to public health researchers by the Centers for Disease Control and Prevention (CDC) via the Wide-ranging Online Data for Epidemiologic Research (WONDER) system. This addition of heat stress measures to CDC WONDER allows decision and policy makers to assess the impact of alternative approaches to optimize the public health response to EHEs. Through CDC WONDER, users are able to spatially and temporally query public health and heat-related data sets and create county-level maps and statistical charts of such data across the coterminous U.S.

Quattrochi, Dale A.↗

High Frequency QRS ECG Accurately Detects Cardiomyopathy

High frequency (HF, 150-250 Hz) analysis over the entire QRS interval of the ECG is more sensitive than conventional ECG for detecting myocardial ischemia. However, the accuracy of HF QRS ECG for detecting cardiomyopathy is unknown. We obtained simultaneous resting conventional and HF QRS 12-lead ECGs in 66 patients with cardiomyopathy (EF = 23.2 plus or minus 6.l%, mean plus or minus SD) and in 66 age- and gender-matched healthy controls using PC-based ECG software recently developed at NASA. The single most accurate ECG parameter for detecting cardiomyopathy was an HF QRS morphological score that takes into consideration the total number and severity of reduced amplitude zones (RAZs) present plus the clustering of RAZs together in contiguous leads. This RAZ score had an area under the receiver operator curve (ROC) of 0.91, and was 88% sensitive, 82% specific and 85% accurate for identifying cardiomyopathy at optimum score cut-off of 140 points. Although conventional ECG parameters such as the QRS and QTc intervals were also significantly longer in patients than controls (P less than 0.001, BBBs excluded), these conventional parameters were less accurate (area under the ROC = 0.77 and 0.77, respectively) than HF QRS morphological parameters for identifying underlying cardiomyopathy. The total amplitude of the HF QRS complexes, as measured by summed root mean square voltages (RMSVs), also differed between patients and controls (33.8 plus or minus 11.5 vs. 41.5 plus or minus 13.6 mV, respectively, P less than 0.003), but this parameter was even less accurate in distinguishing the two groups (area under ROC = 0.67) than the HF QRS morphologic and conventional ECG parameters. Diagnostic accuracy was optimal (86%) when the RAZ score from the HF QRS ECG and the QTc interval from the conventional ECG were used simultaneously with cut-offs of greater than or equal to 40 points and greater than or equal to 445 ms, respectively. In conclusion 12-lead HF QRS ECG employing RAZ scoring is a simple, accurate and inexpensive screening technique for cardiomyopathy. Although HF QRS ECG is highly sensitive for cardiomyopathy, its specificity may be compromised in patients with cardiac pathologies other than cardiomyopathy, such as uncomplicated coronary artery disease or multiple coronary disease risk factors. Further studies are required to determine whether HF QRS might be useful for monitoring cardiomyopathy severity or the efficacy of therapy in a longitudinal fashion.

Schlegel, Todd T.↗

A Multi-Omics Approach Demonstrates that Spaceflight Leads to Lipid Accumulation in Mouse Livers

Spaceflight has several detrimental effects on the physiology of astronauts, many of which are recapitulated in rodent models. We analyzed liver transcriptomic and proteomic data from three mouse spaceflight experiments flown aboard the International Space Station (Rodent Research-1 NASA (RR-1 NASA), Rodent Research-1 CASIS (RR-1 CASIS), Rodent Research-3 (RR-3)), and one mouse experiment flown on the Space Shuttle (Commercial Biomedical Testing Module-3 (CBTM-3) aboard STS-135). Despite the differences in genetic background and time of exposure to microgravity it was shown through Oil Red staining and histology that increased lipid accumulation was occurring in the liver of all mice flown in space compared to the ground controls. This led to further pursue the existing GeneLab datasets related to liver omics data from these mice. We were able to discover key conserved pathways across all the mice independent of the flight conditions that were related to increased lipid metabolism, fatty acid metabolism, both lipid and fatty acid processing, lipid catabolic processing, and lipid localization. In addition, key upstream regulators were predicted to be commonly regulated across all conditions which include ESR1, GCG, and NR1I2 being inhibited and INS being activated. Interestingly, estrogen receptor alpha (ESR1) expression has been known to be heavily involved with lipoprotein metabolism. In addition, insulin (INS) is the primary driver for fat metabolism and increased INS has been associated with increased fatty acids in the liver. Through additional proteomic analysis we were able to identify the majority of the key proteins related to lipids for both the RR-1 and RR-3 rodents were being up-regulated in the livers when comparing flight to ground controls. This additional confirmation of the lipid associated activity also showed that the lipid related proteins are heavily involved with lipid metabolism, cholesterol binding, and cholesterol metabolism. Lastly, the analysis also revealed that the circadian clock related pathways in the liver are commonly being increased across all space flight conditions which has also been reported in the literature to potentially cause increased liver damage. The combination of the very strong lipid uptake in the liver and the transcriptomic/proteomic signatures (including the circadian clock pathways) following spaceflight are consistent with early onset of liver disease. Taken together, these data indicate that, activation of lipotoxic pathways could persist during longer duration spaceflight which might result in the development of liver disease

Lipids↗

Entire expressed peripheral blood transcriptome in pediatric severe malarial anemia

Abstract This study on severe malarial anemia (SMA: Hb < 6.0 g/dL), a leading global cause of childhood morbidity and mortality, compares the entire expressed whole blood host transcriptome between Kenyan children (3-48 mos.) with non-SMA (Hb ≥ 6.0 g/dL, n = 39) and SMA ( n = 18). Differential expression analyses reveal 1403 up-regulated and 279 down-regulated transcripts in SMA, signifying impairments in host inflammasome activation, cell death, and innate immune and cellular stress responses. Immune cell profiling shows decreased memory responses, antigen presentation, and immediate pathogen clearance, suggesting an immature/improperly regulated immune response in SMA. Module repertoire analysis of blood-specific gene signatures identifies up-regulation of erythroid genes, enhanced neutrophil activation, and impaired inflammatory responses in SMA. Enrichment analyses converge on disruptions in cellular homeostasis and regulatory pathways for the ubiquitin-proteasome system, autophagy, and heme metabolism. Pathway analyses highlight activation in response to hypoxic conditions [Hypoxia Inducible Factor (HIF)−1 target and Reactive Oxygen Species (ROS) signaling] as a central theme in SMA. These signaling pathways are also top-ranking in protein abundance measures and a Ugandan SMA cohort with available transcriptomic data. Targeted RNA-Seq validation shows strong concordance with our entire expressed transcriptome data. These findings identify key molecular themes in SMA pathogenesis, offering potential targets for new malaria therapies.

60 APPLIED LIFE SCIENCES↗

It's the Heat AND the Humidity -- Assessment of Extreme Heat Scenarios to Enable the Assessment of Climate Impacts on Public Health

In the United States, extreme heat is the most deadly weather-related hazard. In the face of a warming climate and urbanization, which contributes to local-scale urban heat islands, it is very likely that extreme heat events (EHEs) will become more common and more severe in the U.S. In a NASA-funded project supporting the National Climate Assessment, we are providing historical and future measures of extreme heat to enable assessments of the impacts of heat on public health over the coterminous U.S. We use atmospheric temperature and humidity information from meteorological reanalysis and from Global Climate Models (GCMs) to provide data on past and future heat events. The project s emphasis is on providing assessments of the magnitude, frequency and geographic distribution of extreme heat in the U.S. to facilitate public health studies. In our approach, long-term climate change is captured with GCM output, and the temporal and spatial characteristics of short-term extremes are represented by the reanalysis data. Two future time horizons, 2040 and 2090, are the focus of future assessments; these are compared to the recent past period of 1981-2000. We are characterizing regional-scale temperature and humidity conditions using GCM output for two climate change scenarios (A2 and A1B) defined in the Special Report on Emissions Scenarios (SRES). For each future period, 20 years of multi-model GCM output have been analyzed to develop a heat stress climatology based on statistics of extreme heat indicators. Differences between the two future and past periods have been used to define temperature and humidity changes on a monthly time scale and regional spatial scale. These changes, combined with hourly historical meteorological data at a spatial scale (12 km) much finer than that of GCMs, enable us to create future climate realizations, from which we compute the daily heat stress measures and related spatially-specific climatological fields. These include the mean annual number of days above certain thresholds of maximum and minimum air temperatures, heat indices and a new heat stress variable that gives an integrated measure of heat stress (and relief) over the course of a day. Comparisons are made between projected (2040 and 2090) and past (1990) heat stress statistics. All output is being provided at the 12 km spatial scale and will also be aggregated to the county level, which is a popular scale of analysis for public health researchers. County-level statistics will be made available by our collaborators at the Centers for Disease Control and Prevention (CDC) via the Wide-ranging Online Data for Epidemiologic Research (WONDER) system. CDC WONDER makes the information resources of the CDC available to public health professionals and the general public. This addition of heat stress measures to CDC WONDER will allow decision and policy makers to assess the impact of alternative approaches to optimize the public health response to EHEs. It will also allow public health researchers and policy makers to better include such heat stress measures in the context of national health data available in the CDC WONDER system. The users will be able to spatially and temporally query public health and heat-related data sets and create county-level maps and statistical charts of such data across the coterminous U.S.

Crosson, William L↗