14. Ten Years of Vegetation Observations on Formerly Grazed Oklahoma Grassland

In summer 2003, we established a series of 40 adjacent, 10310-m blocks in formerly grazed grassland in southcentral Oklahoma. The blocks were allowed to rest and received no grazing, mowing, or burning. We tracked changes in the vegetation of the site over time between 2005 and 2015. Frequency sampling of prairie vegetation was performed at irregular intervals. In spring 2006 we seeded half the site with a Texas/Oklahoma prairie forb mix. We found no significant trends of change in species richness or diversity over time. However, there were subtle changes in abundance of individual species. Across fall sampling periods, Shannon diversity ranged from 1.1 to 1.3, and species richness ranged from 29 to 41, with higher richness and diversity in the sole spring sample. The percentage of nonnative species present at the site ranged from 13 to 18%. The earliest samples showed that the dominant grass species were little bluestem (Schizachyrium scoparium (Michx.) Nash), three-awn (Aristida oligantha Michx.), and Scribner’s panic grass (Dichanthelium oligosanthes (Schult.) Gould). The dominant forb present was ragweed (Ambrosia artemesiifolia L.). By the end of the 10-year time period, little bluestem had declined in relative frequency and Scribner’s panic grass and three-awn had increased in frequency. Among forbs, sumpweed (Iva annua L.) had entered the site and become a dominant forb, heath aster (Symphyotricum ericoides (L.) G.L. Nesom) increased in frequency, and ragweed abundance fluctuated over time. The most commonly encountered nonnative species were Bermuda grass (Cynodon dactylon (L.) Pers.), singletary-pea (Lathyrus hirsutus L.), and sericea lespedeza (Lespedeza cuneata (Dum. Cours.) G. Don.), but none of these species increased in abundance over time. In addition, there was anecdotal evidence of woody species encroachment on the site, mostly winged elm (Ulmus alata Michx.), wild plum (Prunus sp.), and red cedar (Juniperus virginiana L.). Establishment of the prairie mix appears to have been unsuccessful. In this study, cessation of grazing (‘‘resting’’ a site) alone did not allow for recovery of prairie vegetation and may have permitted invasion of undesirable herbaceous and woody species

Laboratory Studies of Allelopathic Effects of Juniperus Virginiana L. on Five Species of Native Plants

Juniperus virginiana L. (eastern redcedar) is known as an encroaching native plant species. It poses particular problems in the Great Plains, where fire suppression in the 20th century has led to the expansion of its population and the area it affects. There is some evidence that the genus Juniperus contains members that are allelopathic; work with western species of juniper have demonstrated negative effects of litter on seedling growth. We established laboratory experiments to test the effect of a water leachate of eastern redcedar litter (100 g litter per liter DI water; steeped 8 h) and eastern redcedar litter on the growth and germination of five native herbaceous species. We saw no clear negative effect of leachate or litter; in fact, there is limited evidence that the leachate increased percent germination, and the presence of litter may have led to greater height growth in inland sea-oats. There was no evidence of the litter or leachate acidifying the soil, at least over the short course of the experiment. It is possible the main negative effect of the presence of eastern redcedar on herbaceous species is through light or nutrient competition by mature trees. We are repeating this study in a field setting

Towards an Intelligent Tutor for Mathematical Proofs

Computer-supported learning is an increasingly important form of study since it allows for independent learning and individualized instruction. In this paper, we discuss a novel approach to developing an intelligent tutoring system for teaching textbook-style mathematical proofs. We characterize the particularities of the domain and discuss common ITS design models. Our approach is motivated by phenomena found in a corpus of tutorial dialogs that were collected in a Wizard-of-Oz experiment. We show how an intelligent tutor for textbook-style mathematical proofs can be built on top of an adapted assertion-level proof assistant by reusing representations and proof search strategies originally developed for automated and interactive theorem proving. The resulting prototype was successfully evaluated on a corpus of tutorial dialogs and yields good results.Comment: In Proceedings THedu'11, arXiv:1202.453

T-Cell Assays for Tuberculosis Infection: Deriving Cut-Offs for Conversions Using Reproducibility Data

Although interferon-gamma release assays (IGRA) are promising alternatives to the tuberculin skin test, interpretation of repeated testing results is hampered by lack of evidence on optimal cut-offs for conversions and reversions. A logical start is to determine the within-person variability of T-cell responses during serial testing.We performed a pilot study in India, to evaluate the short-term reproducibility of QuantiFERON-TB Gold In Tube assay (QFT) among 14 healthcare workers (HCWs) who underwent 4 serial QFT tests on day 0, 3, 9 and 12. QFT ELISA was repeated twice on the same sets of specimens. We assessed two types of reproducibility: 1) test-retest reproducibility (between-test variability), and 2) within-person reproducibility over time. Test-retest reproducibility: with dichotomous test results, extremely high concordance was noticed between two tests performed on the same sets of specimens: of the 56 samples, the test and re-test results agreed for all but 2 individuals (kappa = 0.94). Discordance was noted in subjects who had IFN-gamma values around the cut-off point, with both increases and decreases noted. With continuous IFN-gamma results, re-test results tended to produce higher estimates of IFN-gamma than the original test. Within-person reproducibility: when continuous IFN-gamma data were analyzed, the within-person reproducibility was moderate to high. While persons with negative QFT results generally stayed negative, positive results tended to vary over time. Our data showed that increases of more than 16% in the IFN-gamma levels are statistically improbable in the short-term.Conservatively assuming that long-term variability might be at least twice higher than short-term, we hypothesize that a QFT conversion requires two conditions to be met: 1) change from negative to positive result, and 2) at least 30% increase in the baseline IFN-gamma response. Larger studies are needed to confirm our preliminary findings, and determine the conversion thresholds for IGRAs

The genetic landscape of high-risk neuroblastoma

Neuroblastoma is a malignancy of the developing sympathetic nervous system that often presents with widespread metastatic disease, resulting in survival rates of less than 50%1. To determine the spectrum of somatic mutation in high-risk neuroblastoma, we studied 240 cases using a combination of whole exome, genome and transcriptome sequencing as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Here we report a low median exonic mutation frequency of 0.60 per megabase (0.48 non-silent), and remarkably few recurrently mutated genes in these tumors. Genes with significant somatic mutation frequencies included ALK (9.2% of cases), PTPN11 (2.9%), ATRX (2.5%, an additional 7.1% had focal deletions), MYCN (1.7%, a recurrent p.Pro44Leu alteration), and NRAS (0.83%). Rare, potentially pathogenic germline variants were significantly enriched in ALK, CHEK2, PINK1, and BARD1. The relative paucity of recurrent somatic mutations in neuroblastoma challenges current therapeutic strategies reliant upon frequently altered oncogenic drivers

Setting research priorities to improve global newborn health and prevent stillbirths by 2025

Acknowledgements: The authors thank the expert group for their time and effort in this priority–setting exercise, and the contribution of anonymous reviewers to the final version of this report. We acknowledge inputs from Dr Diane Morof from Centers for Disease Control and Prevention, USA. Funding: This work was supported by Save the Children.Peer reviewedPublisher PD

Setting research priorities to improve global newborn health and prevent stillbirths by 2025.

BACKGROUND: In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013-2025. METHODS: We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts. RESULTS: Nine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour. CONCLUSION: These findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed

Setting research priorities to improve global newborn health and prevent stillbirths by 2025

Background In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013-2025. Methods We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts. Results Nine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour. Conclusion These findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

A Comparison of Illinois Remnant Prairies, 1976 to 1988

At one time, 60% of Illinois\u27 land area was covered with prairie, but 99% of that prairie has been lost. Currently, 2,300 acres (about 930 hectares) of remnant prairie is protected in the Illinois Nature Preserves System. Many of these sites were surveyed in the mid-1970s as part of the Illinois Natural Areas Inventory (lNA!). 1 analyzed vegetation data as relative frequency of herbaceous species. Data were analyzed using Detrended Correspondence Analysis (DCA) to determine environmental influences on species composition. I also resampled 29 of the original sites in summer 1998. In addition to collecting data on relative frequency of prairie species, I collected soils and had them analyzed for texture and nutrient availability. In both the 1970s and 1998 samples, moisture availability as related to a topographic gradient was the major environmental fac tor affecting species distribution and abundance. For the 1998 samples, there were relationships between ordinat ion axis scores and soil nutrients, but soil nutrients were not a major factor affecting species composition. When the 1970s and 1998 samples were compared, there were no major changes in species composition, but there were changes in species abundance. There was no conclusive evidence for loss of species from any sites, although there was an increase in abundance of introduced Eurasian weedy species between the 1970s and 1998