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The search for life in the Universe is a fundamental problem of astrobiology and modern science. The current progress in the detection of terrestrial-type exoplanets has opened a new avenue in the characterization of exoplanetary atmospheres and in the search for biosignatures of life with the upcoming ground-based and space missions. To specify the conditions favourable for the origin, development and sustainment of life as we know it in other worlds, we need to understand the nature of global (astrospheric), and local (atmospheric and surface) environments of exoplanets in the habitable zones (HZs) around G-K-M dwarf stars including our young Sun. Global environment is formed by propagated disturbances from the planet-hosting stars in the form of stellar flares, coronal mass ejections, energetic particles and winds collectively known as astrospheric space weather. Its characterization will help in understanding how an exoplanetary ecosystem interacts with its host star, as well as in the specification of the physical, chemical and biochemical conditions that can create favourable and/or detrimental conditions for planetary climate and habitability along with evolution of planetary internal dynamics over geological timescales. A key linkage of (astro)physical, chemical and geological processes can only be understood in the framework of interdisciplinary studies with the incorporation of progress in heliophysics, astrophysics, planetary and Earth sciences. The assessment of the impacts of host stars on the climate and habitability of terrestrial (exo)planets will significantly expand the current definition of the HZ to the biogenic zone and provide new observational strategies for searching for signatures of life. The major goal of this paper is to describe and discuss the current status and recent progress in this interdisciplinary field in light of presentations and discussions during the NASA Nexus for Exoplanetary System Science funded workshop ‘Exoplanetary Space Weather, Climate and Habitability’ and to provide a new roadmap for the future development of the emerging field of exoplanetary science and astrobiology.
A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.
Measurements on the heat affected zone of a weldment are presented using a gas filled position sensitive detector and a normal diffractometer equipped with a scintillation detector and a solid state detector. The sample, a surface ground titanium alloy, provided a difficult application for the X-ray technique from which a test of the real usefulness of the position sensitive detector could be made. The diffraction profile from the Ti alloy is very broad and the fluorescence produces a high background. The fluorescence is easily rejected using a solid state detector; however, the time of analysis is very long. With the position sensitive detector, the combination of increased energy discrimination over the scintillation detector and the simultaneous measurement of many data points over the broad peak enabled the measurements to be made for the same accuracy in much shorter times than for either the solid state detector or the scintillation detector.
Software is described for complete computer control of residual stress measurements. One program (that incorporates either the two tilt method, the sins| procedure, or the Cohen-Marion technique) has been developed for use with either a normal detector or a position sensitive detector. The operator inputs the desired error in stress and various instrumental parameters that determine systematic errors. The counting strategy to obtain the total error is then determined by the software.
Employing this automated system, an investigation of a parabolic fit to the top of a diffraction profile indicates that a three point fit is satisfactory only for sharp profiles.
The internal stress state in a Al2O3-SiC composite has been studied with X-ray diffraction and with calculations with a modified Eshelby model. The influence (on the internal stress state) of volume fraction, temperature, geometric shape, and the orientation of the silicon carbide particles are discussed. The stress tensors were measured in both the matrix and in the reinforcing phase, and the macro- and microstresses were separated for ail the components. Good agreement with the microstresses for the Eshelby model is found in all cases.
Results from X-ray diffraction experiments at low temperature (45-295 K) on the coefficient of thermal expansion are also presented.
In recent years considerable success has been achieved in the development of detectors for the localization of ionizing radiation. One dimensional position sensitive detectors have a number of uses in nuclear physics and in biological studies utilizing small-angle scattering. Detectors are now capable of providing position information of high resolution with a high count rats capability and a simple readout system. We report here on the feasibility of employing a position sensitive proportional counter (PSPC) for the measurement of residual stresses with X-rays.
Comparisons of the accuracy and time of data accumulation between a scintillation detector and a PSPC have been performed on stress relieved, shot peened steel specimens, and specimens deformed in tension.
The ability of obtaining the entire profile at once is somewhat offset by the lower efficiency of the PSPC when compared to a scintillation detector, but this is counteracted by the fact that motion of the detector is eliminated with the PSPC, It will be shown that a PSPC system provides a speed of data accumulation currently not available in any other way, while still remaining a versatile and accurate method.
OBJECTIVES/SPECIFIC AIMS: Objective: Approximately 86 million people in the US have prediabetes, but only a fraction of them receive proven effective therapies to prevent diabetes. Further, the effectiveness of these therapies varies with individual risk of progression to diabetes. We estimated the value of targeting those individuals at highest diabetes risk for treatment, compared to treating all individuals meeting inclusion criteria for the Diabetes Prevention Program (DPP). METHODS/STUDY POPULATION: METHODS: Using a micro-simulation model, we estimated total lifetime costs and quality-adjusted life expectancy (QALE) for individuals receiving: (1) lifestyle intervention involving an intensive program focused on healthy diet and exercise, (2) metformin administration, or (3) no intervention. The model combines several components. First a Cox proportional hazards model predicted onset of diabetes from baseline characteristics for each pre-diabetic individual and yielded a probability distribution for each alternative. We derived this risk model from the Diabetes Prevention Program (DPP) clinical trial data and the follow-up study DPP-OS. The Michigan Diabetes Research Center Model for Diabetes then estimated costs and outcomes for individuals after diabetes diagnosis using standard of care diabetes treatment. Based on individual costs and QALE, we evaluated NMB of the two interventions at population and individual levels, stratified by risk quintiles for diabetes onset at 3 years. RESULTS/ANTICIPATED RESULTS: Results: Compared to usual care, lifestyle modification conferred positive benefits for all eligible individuals. Metformin’s NMB was negative for the lowest population risk quintile. By avoiding use among individuals who would not benefit, targeted administration of metformin conferred a benefit of $500-$800 per person, depending on duration of treatment effect. When treating only 20% of the population (e.g., due to capacity constraints), targeting conferred a NMB of $14,000-$18,000 per person for lifestyle modification and $16,000-$20,000 for metformin. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusions: Metformin confers value only among higher risk individuals, so targeting its use is worthwhile. While lifestyle modification confers value for all eligible individuals, prioritizing the intervention to high risk patients when capacity is constrained substantially increases societal benefits.
Hepatitis E virus (HEV) is an emerging cause of viral hepatitis worldwide. Recently, HEV-7 has been shown to infect camels and humans. We studied HEV seroprevalence in dromedary camels and among Bedouins, Arabs (Muslims, none-Bedouins) and Jews and assessed factors associated with anti-HEV seropositivity. Serum samples from dromedary camels (n = 86) were used to determine camel anti-HEV IgG and HEV RNA positivity. Human samples collected between 2009 and 2016 from >20 years old Bedouins (n = 305), non-Bedouin Arabs (n = 320) and Jews (n = 195), were randomly selected using an age-stratified sampling design. Human HEV IgG levels were determined using Wantai IgG ELISA assay. Of the samples obtained from camels, 68.6% were anti-HEV positive. Among the human populations, Bedouins and non-Bedouin Arabs had a significantly higher prevalence of HEV antibodies (21.6% and 15.0%, respectively) compared with the Jewish population (3.1%). Seropositivity increased significantly with age in all human populations, reaching 47.6% and 34.8% among ⩾40 years old, in Bedouins and non-Bedouin Arabs, respectively. The high seropositivity in camels and in ⩾40 years old Bedouins and non-Bedouin Arabs suggests that HEV is endemic in Israel. The low HEV seroprevalence in Jews could be attributed to higher socio-economic status.
We aimed to explore the range of stakeholders’ perceptions of the Balance Calories Initiative (BCI), under which the American Beverage Association pledged to decrease per capita US consumption of beverage energy by 20 % by 2025.
Semi-structured cross-sectional interviews were conducted in 2017.
Participants were recruited from communities targeted by the BCI (Montgomery, AL; North Mississippi Delta, MS; Eastern Los Angeles, CA).
A total of thirty-three parents and thirty-eight youths aged 10–17 years were recruited through youth-serving organizations, street intercept and snowball sampling; sixteen store/restaurant managers were recruited at businesses. Participants were asked about their awareness of the BCI. Parents and youths were asked to ‘think aloud’ as they viewed BCI messages (e.g. ‘Balance What You Eat, Drink, and Do’) and managers were asked about beverage marketing.
Twelve parents and twenty-four youths had seen BCI messages; only four managers were aware of the BCI. Many parents and youths showed some misunderstanding of BCI messages (e.g. that they should drink more sugar-sweetened beverages (SSB) or they needed to equalize healthy and unhealthy beverage intake). Only one manager had communicated with beverage companies about the BCI.
We found mixed comprehension and low awareness of BCI messages in communities targeted by the American Beverage Association for reduced SSB consumption. Industry self-regulation attempts to reduce SSB consumption may have limited effectiveness if stakeholder input is not addressed. Public health practitioners should be aware of the need to address youths’ and parents’ misunderstandings about SSB consumption, especially in BCI-targeted communities.
There is absence knowledge about the effects of lactation trimester and parity on eating behavior, production and efficiency of dairy cows. Objective of this study was to identify and characterize in 340 dairy cows, the 20% high efficient (HE), 20% low efficient (LE) and 60% mid efficient (ME) cows according to their individual residual feed intake (RFI) values, within and between lactation trimesters and between 1st and 2nd parities. Efficiency effect within each lactation trimester, was exhibited in daily dry matter intake (DMI), eating rate and meal size, that were the highest in LE cows, moderate in the ME cows and lowest in the HE group. Daily eating time, meal frequency, yields of milk and energy-corrected milk (ECM) and BW were similar in the three efficiency groups within each trimester. The lower efficiency of the LE cows in each trimester attributes to their larger metabolic energy intake, heat production and energy losses. In subgroup of 52 multiparous cows examined along their 1st and 2nd trimesters, milk and ECM production, DMI, eating behavior and efficiency traits were similar with high Pearson’s correlation (r=0.78 to 0.89) between trimesters. In another subgroup of 42 multiparous cows measured at their 2nd and 3rd trimesters, milk and ECM yield, DMI and eating time were reduced (P<0.01) at the 3rd trimester, but eating rate, meal frequency and meal size remained similar with high Pearson’s correlation (r=0.74 to 0.88) between trimesters. In subgroup of 26 cows measured in 1st and 2nd parities, DMI, BW, milk and ECM yield, and ECM/DMI increased in the 2nd lactation, but eating behavior and RFI traits were similar in both parities. These findings encourage accurate prediction of DMI based on a model that includes eating behavior parameters, together with individual measurement of ECM production. This can be further used to identify HE cows in commercial herd, a step necessary for potential genetic selection program aimed to improve herd efficiency.
Rising sea levels due to climate change can have severe consequences for coastal populations and ecosystems all around the world. Understanding and projecting sea-level rise is especially important for low-lying countries such as the Netherlands. It is of specific interest for vulnerable ecological and morphodynamic regions, such as the Wadden Sea UNESCO World Heritage region.
Here we provide an overview of sea-level projections for the 21st century for the Wadden Sea region and a condensed review of the scientific data, understanding and uncertainties underpinning the projections. The sea-level projections are formulated in the framework of the geological history of the Wadden Sea region and are based on the regional sea-level projections published in the Fifth Assessment Report of the Intergovernmental Panel on Climate Change (IPCC AR5). These IPCC AR5 projections are compared against updates derived from more recent literature and evaluated for the Wadden Sea region. The projections are further put into perspective by including interannual variability based on long-term tide-gauge records from observing stations at Den Helder and Delfzijl.
We consider three climate scenarios, following the Representative Concentration Pathways (RCPs), as defined in IPCC AR5: the RCP2.6 scenario assumes that greenhouse gas (GHG) emissions decline after 2020; the RCP4.5 scenario assumes that GHG emissions peak at 2040 and decline thereafter; and the RCP8.5 scenario represents a continued rise of GHG emissions throughout the 21st century. For RCP8.5, we also evaluate several scenarios from recent literature where the mass loss in Antarctica accelerates at rates exceeding those presented in IPCC AR5.
For the Dutch Wadden Sea, the IPCC AR5-based projected sea-level rise is 0.07±0.06m for the RCP4.5 scenario for the period 2018–30 (uncertainties representing 5–95%), with the RCP2.6 and RCP8.5 scenarios projecting 0.01m less and more, respectively. The projected rates of sea-level change in 2030 range between 2.6mma−1 for the 5th percentile of the RCP2.6 scenario to 9.1mma−1 for the 95th percentile of the RCP8.5 scenario. For the period 2018–50, the differences between the scenarios increase, with projected changes of 0.16±0.12m for RCP2.6, 0.19±0.11m for RCP4.5 and 0.23±0.12m for RCP8.5. The accompanying rates of change range between 2.3 and 12.4mma−1 in 2050. The differences between the scenarios amplify for the 2018–2100 period, with projected total changes of 0.41±0.25m for RCP2.6, 0.52±0.27m for RCP4.5 and 0.76±0.36m for RCP8.5. The projections for the RCP8.5 scenario are larger than the high-end projections presented in the 2008 Delta Commission Report (0.74m for 1990–2100) when the differences in time period are considered. The sea-level change rates range from 2.2 to 18.3mma−1 for the year 2100.
We also assess the effect of accelerated ice mass loss on the sea-level projections under the RCP8.5 scenario, as recent literature suggests that there may be a larger contribution from Antarctica than presented in IPCC AR5 (potentially exceeding 1m in 2100). Changes in episodic extreme events, such as storm surges, and periodic (tidal) contributions on (sub-)daily timescales, have not been included in these sea-level projections. However, the potential impacts of these processes on sea-level change rates have been assessed in the report.
Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentation and, likely, underlying pathophysiology. Accordingly, it is possible that only certain individuals with MDD are well-suited to antidepressants. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression, such as neuroticism, anhedonia, and cognitive control deficits.
Within an 8-week multisite trial of sertraline v. placebo for depressed adults (n = 216), we examined whether the combination of machine learning with a Personalized Advantage Index (PAI) can generate individualized treatment recommendations on the basis of endophenotype profiles coupled with clinical and demographic characteristics.
Five pre-treatment variables moderated treatment response. Higher depression severity and neuroticism, older age, less impairment in cognitive control, and being employed were each associated with better outcomes to sertraline than placebo. Across 1000 iterations of a 10-fold cross-validation, the PAI model predicted that 31% of the sample would exhibit a clinically meaningful advantage [post-treatment Hamilton Rating Scale for Depression (HRSD) difference ⩾3] with sertraline relative to placebo. Although there were no overall outcome differences between treatment groups (d = 0.15), those identified as optimally suited to sertraline at pre-treatment had better week 8 HRSD scores if randomized to sertraline (10.7) than placebo (14.7) (d = 0.58).
A subset of MDD patients optimally suited to sertraline can be identified on the basis of pre-treatment characteristics. This model must be tested prospectively before it can be used to inform treatment selection. However, findings demonstrate the potential to improve individual outcomes through algorithm-guided treatment recommendations.
Pathogen burden is a construct developed to assess the cumulative effects of multiple, persistent pathogens on morbidity and mortality. Despite the likely biological wear and tear on multiple body systems caused by persistent infections, few studies have examined the impact of total pathogen burden on such outcomes and specifically on preclinical markers of dysfunction. Using data from two waves of the National Health and Nutrition Examination Survey, we compared three alternative methods for measuring pathogen burden, composed of mainly persistent viral infections, using a cumulative deficits index (CDI) as an outcome: single pathogen associations, a pathogen burden summary score and latent class analyses. We found significant heterogeneity in the distribution of the CDI by age, sex, race/ethnicity and education. There was an association between pathogen burden and the CDI by all three metrics. The latent class classification of pathogen burden showed particularly strong associations with the CDI; these associations remained after controlling for age, sex, body mass index, smoking, race/ethnicity and education. Our results suggest that pathogen burden may influence early clinical indicators of poor health as measured by the CDI. Our results are salient since we were able to detect these associations in a relatively young population. These findings suggest that reducing pathogen burden and the specific pathogens that drive the CDI may provide a target for preventing the early development of age-related physiological changes.
OBJECTIVES/SPECIFIC AIMS: This study aims to assess the safety, feasibility, clinical benefits and pharmacodynamics of adding allopurinol to standard maintenance therapy that includes 6-mecaptopurine (6-MP) in pediatric patients with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma. Our goal is to investigate if allopurinol improves hepatotoxicity and GI toxicity, if it safely decreases acute neutrophil count (ANC), if it reduces the 6-MP dose required during chemotherapy, and if it works through our hypothesized mechanism by lowering the levels of the toxic metabolite, 6-methylmecaptopurine (6-MMP) and by raising the levels of the active metabolite, 6-thioguanine (6-TGN). METHODS/STUDY POPULATION: This is a single arm, nonblinded pilot study of patients under age 30 years who were being treated in the maintenance phase of therapy for ALL or lymphoblastic lymphoma, and had adverse effects such as high 6-MMP:6-TGN ratio, high ANC, and high liver enzymes. Patients enrolled were started with allopurinol in addition to ongoing oral chemotherapy. Data from beginning maintenance to end of chemotherapy was collected in the electronic medical record, EPIC for the 13 patients enrolled at Johns Hopkins, and data analysis was conducted using STATA and Excel. RESULTS/ANTICIPATED RESULTS: Initial data analysis reveals that the required dose of 6-MP after addition of allopurinol to the chemotherapy regimen was significantly lower compared with that before the addition of allopurinol in 11 out of the 12 patients assessed (p<0.05). Among the 10 patients that were assessed for 6MMP:6TG ratio, all had lower average 6MMP:6TGN ratios after allopurinol compared to before allopurinol; the percentage of weeks that goal 6MMP:6TGN ratio (<40) were maintained were statistically significant in 6 patients (p<0.05) and close to significance in 2 other patients (p=0.057). The percentage of weeks that patients maintained alanine aminotransferase levels below 120 was significantly greater after addition of allopurinol compared to before the addition of allopurinol in 9 out of 13 patients assessed, suggesting that allopurinol may be associated with reduced hepatotoxicity. Further data analysis is ongoing to assess the percentage of weeks that patients maintained goal total bilirubin, direct bilirubin, and ANC, as well as average number of admissions for infections and average number of therapy holds after allopurinol addition compared to before allopurinol addition. DISCUSSION/SIGNIFICANCE OF IMPACT: Allopurinol is associated with reduction in required 6-MP dose, decrease in the percentage of weeks that patients have hepatotoxicity, and reduction in the ratio of toxic metabolite to active anti-leukemic metabolite in several patients. We hope that the results of this study can be used for further research and for guiding clinical practice since there are no established guidelines in pediatric oncology regarding addressing side effects of oral chemotherapy using 6-MP. If allopurinol indeed is safe and effective, adding it to the standard chemotherapy regimen can lead to better tolerance and compliance to oral maintenance chemotherapy, and hopefully improved outcomes for children with ALL and lymphoblastic leukemia.