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Epoch of Reionisation (EoR) data analysis requires unprecedented levels of accuracy in radio interferometer pipelines. We have developed an imaging power spectrum analysis to meet these requirements and generate robust 21 cm EoR measurements. In this work, we build a signal path framework to mathematically describe each step in the analysis, from data reduction in the Fast Holographic Deconvolution (FHD) package to power spectrum generation in the εppsilon package. In particular, we focus on the distinguishing characteristics of FHD/εppsilon: highly accurate spectral calibration, extensive data verification products, and end-to-end error propagation. We present our key data analysis products in detail to facilitate understanding of the prominent systematics in image-based power spectrum analyses. As a verification to our analysis, we also highlight a full-pipeline analysis simulation to demonstrate signal preservation and lack of signal loss. This careful treatment ensures that the FHD/εppsilon power spectrum pipeline can reduce radio interferometric data to produce credible 21 cm EoR measurements.
We apply two methods to estimate the 21-cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly spaced triangles of antenna tiles, as well as an estimate based on data gridded to the uv-plane. The direct and gridded bispectrum estimators are applied to 21 h of high-band (167–197 MHz; z = 6.2–7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point-source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 h, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21-cm bispectrum may be accessible in less time than the 21-cm power spectrum for some wave modes, with detections in hundreds of hours.
Endophytes have the potential to contribute to the sustainable production of bioenergy crops such as the perennial rhizomatous grass Miscanthus. They can improve plant growth on marginal land that is otherwise unsuitable for conventional agriculture and can also reduce the need for environmentally damaging chemical inputs including fertilisers and pesticides. This chapter outlines current knowledge of Miscanthus endophytes and presents new data on the diversity of root and shoot fungal endophytes isolated from three Miscanthus species (M. sacchariflorus, M. sinensis and M. ×giganteus). Malt extract, potato dextrose and Czapek Dox media were compared for isolation and growth of the endophytes. The endophytes were then identified using DNA barcoding with three DNA loci (nrITS, nrLSU and TEF). nrITS and nrLSU were found to be the most reliable and consistent barcoding regions. Internal transcribed spacer (ITS) had the highest discriminating potential and is thus recommended for single locus barcoding of endophytes in Miscanthus. Most new isolates were Ascomycota belonging to Pezizomycotina with representatives from Dothideomycetes, Eurotiomycetes and Sordariomycetes. One Basidiomycota species was recovered (a known soil yeast Rhodotorula). Comparisons between Miscanthus endophyte species composition and its better-known sister genus Saccharum (including sugarcane) are provided.
The proprietary immediate and extended drug delivery technology LiquiXR™ utilizes an ion-exchange resin that complexes with amphetamine or any other active moiety that can be protonated and is water-soluble. The active drug product forms a complex with ion-exchange polymers contained in the resin, which is then formed into micron-sized particles. Some of these particles are coated with an aqueous, pH-independent polymer designed to provide immediate or sustained release of active drug product. The polymer coating applied to the ion-exchange resin particles is of varying thickness, allowing for programmed, extended release of active drug product. Solid, coating-free particles provide for immediate release of active drug product.
The micron-sized particles are formulated into an appropriate dosage form (solid or chewable tablet, liquid suspension, orally disintegrating tablet, film, or capsules). Active drug product is subsequently released from the dosage form in millions of particles, with the release driven by a combination of ion exchange and diffusion. After drug release, the ion-exchange resin is excreted in the feces.
The release characteristics of LiquiXR™ are programmable and allow for a customized, sustained release of active drug product for up to 24hours post-dose. Mechanistically, drug particles enter the gastrointestinal tract. As positively-charged ions from gastrointestinal (GI) fluids diffuse across the coating, ionically-charged drug product diffuses through the coating and into the GI fluids for absorption. As the coating is of variable thickness, some drug product takes longer to diffuse and absorb, providing for the programmable delayed drug release characteristic.
The LiquiXR™ drug delivery technology is utilized in Dyanavel® XR (amphetamine extended-release oral suspension; AMPH EROS), which is indicated for the treatment of attention-deficit hyperactivity disorder. It comprises 2.5mg/mL amphetamine base complexed with LiquiXR technology to provide an immediate release component followed by an extended-release profile. The efficacy of AMPH EROS was established in children ages 6 to 12 years in a Phase 3, placebo-controlled laboratory classroom study. In that study, attention-deficit/hyperactivity disorder (ADHD) symptoms in children on an individually optimized dose of amphetamine (range 10–20mg/day) were statistically significantly improved compared with symptoms in children treated with placebo. For children treated with AMPH EROS, onset of effect was demonstrated at 1hour after dosing, and efficacy was observed through 13hours post-dose. The effect size was comparable to effect sizes demonstrated for other psychostimulants tested in studies using a similar design. The efficacy data reported for AMPH EROS provides an excellent example of the potential utility and clinical application for other active drug products requiring an immediate release and extended release profile.
Funding Acknowledgements: This work was funded by Tris Pharma, Inc.
To determine whether amphetamine extended-release oralsuspension (AMPH EROS) has an onset of effect at 30minutes postdose inchildren with ADHD.
This randomized, double-blind, 2-treatment, 2-sequence, placebo-controlled crossover pilot study enrolled subjects aged 6 to 12 years withattention-deficit/hyperactivity disorder (ADHD) and ADHD-Rating Scale-5 scores of ≥90th percentile for sex and age. A dose of 5 to 20mg/day of AMPH EROS was determined during a 1-week open-label phase based on medication history, symptom control, and tolerability. Subjects completed a practice laboratory classroom then received one day of double-blind active drug or placebo each in random sequence during 2 double-blind laboratory classroom days. Subjects completed the first double-blind laboratory classroom session, returned to open label drug for 5days then crossed over on day 6 during a second double-blind laboratory classroom session. DB dose was fixed at AMPH EROS 15, 17.5, or 20mg . The primary endpoint was change from predose in the Swanson, Kotkin, Agler, M-Flynn, Pelham rating scale-combined score (SKAMP-C) at 30minutes postdose on two DB days. The key secondary endpoint was change from predose in the SKAMP-C score at 3hours postdose for AMPH EROS compared with placebo. Safety assessments included vital signs and adverse events.
Eighteen subjects were enrolled in the study (14 males and 4 females) with a mean age of 9 years. At both 30minutes and 3hours postdose, changes from baseline in SKAMP-C for AMPH EROS vs. placebo were statistically significant (p<0.01 and p=0.0002, respectively) with corresponding effect sizes of 0.96 and 1.57. Adverse events (>10%) during the open-label phase included upper respiratory tract infection, fatigue, upper abdominal pain, headache, decreased appetite, and affect lability.
AMPH EROS was effective in reducing ADHD symptoms at 30minutes postdose. AEs were mild or moderate and consistent with those of other extended-release amphetamines.
Funding Acknowledgements: Support was provided by Tris Pharma, Inc.
Report the efficacy of open-label amphetamine extended-release oral suspension (AMPH EROS) for the treatment of children with ADHD.
AMPH EROS has a 1-hr onset of effect and a duration of action of 13hours and was approved by FDA for treatment of ADHD in children aged 6–17 years based on a double-blind, placebo-controlled efficacy and safety study in children aged 6–12 years with ADHD. A significant treatment difference in change from pre-dose SKAMP-combined score was observed at the primary endpoint of 4hours post-dose (p<0.0001) and each post-dose time point assessed (1, 2, 4, 6, 8, 10, 12, 13hours).
Data reported here are from the 5-week, open-label dose optimization period. These efficacy data support the primary endpoint result.
Males and females aged 6 to 12 years with ADHD enrolled and began open-label treatment with 2.5 mg or 5mg/day of AMPH EROS titrated in 2.5–10mg/day increments until optimal dose (maximum 20mg/day). Doses could be decreased for tolerability. Subjects took morning AMPH EROS for 5weeks. Other efficacy outcomes during the open-label dose optimization phase: ADHD-RS (ADHD-Rating Scale), CGI-S (Clinical Global Impression of Severity), CGI-I (CGI-of Improvement) and CPRS (Conners’ Parent Rating Scale). All subjects were assessed for safety.
For the ITT population (n=99): treatment with AMPH EROS was associated with a mean change in ADHD-RS-IV (baseline to end of the open-label dose optimization; week 6) of 28.2 (±9.03) (Baseline score = 41.3±7.95). 90.9% of subjects had a change from baseline to open-label week 6 of ≥50% in the ADHD-RS-IV total score and were defined as responders. The CGI-S scores decreased continuously from baseline, with a high 4.8 at baseline to a low of 2.0 at open-label week 6. The percentage of subjects classified as moderately ill or greater correspondingly decreased from 97% at Baseline to 1% at open-label week 6. The decrease in the CGI-I over the study was similar to the change in CGI-S scores. CPRS for most categories decreased continuously from Baseline to open-label week 6. Mean change from baseline to open-label week 6 on the CPRS inattention T-score subscale was –25.3 (±14.38) and –24.4 (±13.87).
Adverse events (>5%) reported during dose optimization were decreased appetite, insomnia, affect lability, upper abdominal pain, mood swings and headache.
AMPH EROS was effective in reducing symptoms of ADHD in this open-label dose optimization. The AE profile of AMPH EROS was consistent with those of other amphetamine products.
Funding Acknowledgements: This work was funded by Tris Pharma, Inc.
The proprietary, immediate and extended drug delivery technologyLiquiXR® utilizes an ion-exchange resin that complexes with amphetamine or any active moiety that can be protonated and is water-soluble. The active ingredient of the drug product forms a complex with an ion exchange polymer of the resin resulting in micron-sized particles. A portion of these particles is then coated with an aqueous, pH-independent polymer designed to provide sustained release of drug product. The polymer coating applied to the ion-exchange resin particles is of varying thickness, allowing for extended release of active drug while uncoated particles provide for immediate release of drug.
The micron-sized particles lend themselves to being formulated into an appropriate dosage form: solid/chewable tablet, liquid suspension, orally disintegrating tablet, film, or capsules. Active ingredient of drug product is subsequently released from the dosage form in millions of particles, with release driven by a combination of ion exchange and diffusion. After drug release, the ion-exchange resin particles are excreted in the feces.
The release characteristics of LiquiXR allow for customized, sustained release of active drug ∼24hours post dose. Mechanistically, drug particles enter the gastrointestinal (GI) tract. As positively-charged ions from GI fluids diffuse across the coating, it displaces drug ions from product and they diffuse through the coating and into the GI fluids for absorption. As the coating is of variable thickness, some drug product takes longer to diffuse and absorb, providing for the delayed drug release characteristics.
The LiquiXR drug delivery technology has already been successfully utilized in the development of treatment options (liquid suspension and chewable tablet) that offer rapid absorption and sustained plasma levels after once-daily dosing. LiquiXR is utilized in Dyanavel® XR (amphetamine extended-release oral suspension; AMPH EROS), which is indicated for treatment of ADHD. It comprises 2.5mg/mL amphetamine base and uses LiquiXR technology to provide an immediate release component followed by an extended-release profile.
Efficacy of AMPH EROS was established in children 6 to 12 yr in a Phase 3, placebo-controlled laboratory classroom study. In that study, ADHD symptoms in children on an individually optimized dose of amphetamine (range 10–20mg/day) were statistically significantly improved compared with symptoms in children treated with placebo. For children treated with AMPH EROS, onset of effect was demonstrated at 1hour after dosing, and efficacy was observed through 13hr post-dose. The effect size (ES) was comparable to ES demonstrated for other psychostimulants tested in studies using a similar design. The efficacy data reported for AMPH EROS provides an excellent example of the potential utility and clinical application for other active drug products requiring an immediate and extended release profile.
Funding Acknowledgements: Support provided by Tris Pharma, Inc.
Douglass C. North, co-winner of the Nobel Memorial Prize in Economics in 1993, became a major leader in historical and comparative political science and in the study of institutions more generally. His work proved particularly relevant for those interested in questions of state building, state variation, development, and long-term secular change.
This study investigated the characteristics of subjective memory complaints (SMCs) and their association with current and future cognitive functions.
A cohort of 209 community-dwelling individuals without dementia aged 47–90 years old was recruited for this 3-year study. Participants underwent neuropsychological and clinical assessments annually. Participants were divided into SMCs and non-memory complainers (NMCs) using a single question at baseline and a memory complaints questionnaire following baseline, to evaluate differential patterns of complaints. In addition, comprehensive assessment of memory complaints was undertaken to evaluate whether severity and consistency of complaints differentially predicted cognitive function.
SMC and NMC individuals were significantly different on various features of SMCs. Greater overall severity (but not consistency) of complaints was significantly associated with current and future cognitive functioning.
SMC individuals present distinctive features of memory complaints as compared to NMCs. Further, the severity of complaints was a significant predictor of future cognition. However, SMC did not significantly predict change over time in this sample. These findings warrant further research into the specific features of SMCs that may portend subsequent neuropathological and cognitive changes when screening individuals at increased future risk of dementia.
OBJECTIVES/SPECIFIC AIMS: To build a multisite de-identified database of female adolescents, aged 12–21 years (January 2011–December 2012), and their subsequent offspring through 24 months of age from electronic health records (EHRs) provided by participating Community Health. METHODS/STUDY POPULATION: We created a community-academic partnership that included New York City Community Health Centers (n=4) and Hospitals (n=4), The Rockefeller University, The Sackler Institute for Nutrition Science and Clinical Directors Network (CDN). We used the Community-Engaged Research Navigation model to establish a multisite de-identified database extracted from EHRs of female adolescents aged 12–21 years (January 2011–December 2012) and their offspring through 24 months of age. These patients received their primary care between 2011 and 2015. Clinical data were used to explore possible associations among specific measures. We focused on the preconception, prenatal, postnatal periods, including pediatric visits up to 24 months of age. RESULTS/ANTICIPATED RESULTS: The analysis included all female adolescents (n=122,556) and a subset of pregnant adolescents with offspring data available (n=2917). Patients were mostly from the Bronx; 43% of all adolescent females were overweight (22%) or obese (21%) and showed higher systolic and diastolic blood pressure, blood glucose levels, hemoglobin A1c, total cholesterol, and triglycerides levels compared with normal-weight adolescent females (p<0.05). This analysis was also performed looking at the nonpregnant females and the pregnant females separately. Overall, the pregnant females were older (mean age=18.3) compared with the nonpregnant females (mean age=16.5), there was a higher percentage of Hispanics among the pregnant females (58%) compared with the nonpregnant females (43.9%). There was a statistically significant association between the BMI status of mothers and infants’ birth weight, with underweight/normal-weight mothers having more low birth weight (LBW) babies and overweight/obese mothers having more large babies. The odds of having a LBW baby was 0.61 (95% CI: 0.41, 0.89) lower in obese compared with normal-weight adolescent mothers. The risk of having a preterm birth before 37 weeks was found to be neutral in obese compared with normal-weight adolescent mothers (OR=0.81, 95% CI: 0.53, 1.25). Preliminary associations are similar to those reported in the published literature. DISCUSSION/SIGNIFICANCE OF IMPACT: This EHR database uses available measures from routine clinical care as a “rapid assay” to explore potential associations, and may be more useful to detect the presence and direction of associations than the magnitude of effects. This partnership has engaged community clinicians, laboratory, and clinical investigators, and funders in study design and analysis, as demonstrated by the collaborative development and testing of hypotheses relevant to service delivery. Furthermore, this research and learning collaborative is examining strategies to enhance clinical workflow and data quality as well as underlying biological mechanisms. The feasibility of scaling-up these methods facilitates studying similar populations in different Health Systems, advancing point-of-care studies of natural history and comparative effectiveness research to identify service gaps, evaluate effective interventions, and enhance clinical and data quality improvement.
A considerable loss of nitrogen occurred across the rumen when fresh New Zealand herbages were fed to sheep and live-weight gain of grazing sheep was positively correlated with predicted absorption of amino acids from the small intestine (MacRae and Ulyatt, 1974). This suggests that body growth of young sheep fed some fresh herbages ad libitum may be limited by protein absorption being low in relation to metabolizable energy (ME). The present experiment was designed to test this hypothesis, with special reference to body tissue protein deposition and metabolism, using a diet of ryegrass/white clover pasture.
We present techniques developed to calibrate and correct Murchison Widefield Array low-frequency (72–300 MHz) radio observations for polarimetry. The extremely wide field-of-view, excellent instantaneous (u, v)-coverage and sensitivity to degree-scale structure that the Murchison Widefield Array provides enable instrumental calibration, removal of instrumental artefacts, and correction for ionospheric Faraday rotation through imaging techniques. With the demonstrated polarimetric capabilities of the Murchison Widefield Array, we discuss future directions for polarimetric science at low frequencies to answer outstanding questions relating to polarised source counts, source depolarisation, pulsar science, low-mass stars, exoplanets, the nature of the interstellar and intergalactic media, and the solar environment.
Maruca vitrata (Fabricius, 1787) is a cryptic pantropical species of Lepidoptera that are comprised of two unique strains that inhabit the American continents (New World strain) and regions spanning from Africa through to Southeast Asia and Northern Australia (Old World strain). In this study, we de novo assembled the complete mitochondrial genome sequence of the New World legume pod borer, M. vitrata, from shotgun sequence data generated on an Illumina HiSeq 2000. Phylogenomic comparisons were made with other previously published mitochondrial genome sequences from crambid moths, including the Old World strain of M. vitrata. The 15,385 bp M. vitrata (New World) sequence has an 80.7% A+T content and encodes the 13 protein-coding, 2 ribosomal RNA and 22 transfer RNA genes in the typical orientation and arrangement of lepidopteran mitochondrial DNAs. Mitochondrial genome-wide comparison between the New and Old World strains of M. vitrata detected 476 polymorphic sites (4.23% nucleotide divergence) with an excess of synonymous substitution as a result of purifying selection. Furthermore, this level of sequence variation suggests that these strains diverged from ~1.83 to 2.12 million years ago, assuming a linear rate of short-term substitution. The de novo assemblies of mitochondrial genomes from next-generation sequencing (NGS) reads provide readily available data for similar comparative studies.
Recent 13C solid state nuclear magnetic resonance studies have demonstrated differences in the composition of sporopollenins (the inert biomolecule forming spore and pollen walls) from the major groups of extant plants. This substance is also the main constituent of fossil spore walls.
We have obtained 13C NMR spectra from three species of Carboniferous lycopod megaspores, and in one case, the associated microspores. Additionally, spores from the Devonian plant Parka decipiens Fleming have been analyzed. The spectra obtained are relatively similar although at present it is unclear how much of this similarity results from diagenesis.
The spectra of the fossil spores have been compared to those obtained from extant lycopods and from other plant groups. The fossil lycopod spores share some of the distinctive features of modern lycopod sporopollenin but are, none the less, very different. The spectra of the fossil species also demonstrate the loss of constituents known to form a significant part of the sporopollenin in extant species. Our studies show that some of the chemical characteristics of sporopollenins are retained in fossil spores, allowing the investigation of evolutionary changes of sporopollenin within a group and facilitating the assignment of taxonomically enigmatic fossil species. Further investigation of a range of fossil material, combined with data obtained from pyrolysis, should provide further information on the composition of sporopollenin from different plant groups and on its diagenesis.
The mean, trend and variability of net snow accumulation in firn cores are often used to validate model output, develop remote-sensing algorithms and quantify ice-sheet surface mass balance. Thus, accurately defining uncertainties associated with these in situ measurements is critical. In this study, we apply statistical simulation methods to quantify the uncertainty in firn-core accumulation data due to the uncertainty in depth–age scales. The methods are applied to a suite of firn cores from central West Antarctica. The results show that uncertainty in depth–age scales can give rise to spurious trends in accumulation that are the same order of magnitude as accumulation trends reported in West Antarctica. The depth–age scale uncertainties also significantly increase the apparent interannual accumulation variability, so these uncertainties must first be accounted for before using firn-core data to assess such processes as small-spatial-scale variability. Better quantification of error in accumulation will improve our ability to meaningfully compare firn-core data across different regions of the ice sheet, and provide appropriate targets for calibration and/or validation of model output and remote-sensing data.