Showing papers by "Research Triangle Park published in 2019"
TL;DR: The definition of bronchopulmonary dysplasia that best predicted early childhood morbidity categorized disease severity according to the mode of respiratory support administered at 36 weeks’ postmenstrual age, regardless of supplemental oxygen use.
Abstract: Rationale: Current diagnostic criteria for bronchopulmonary dysplasia rely heavily on the level and duration of oxygen therapy, do not reflect contemporary neonatal care, and do not adequately pred...
437 citations
TL;DR: The proportion of AMI hospitalizations attributable to young patients increased from 1995 to 2014 and was especially pronounced among women, and history of hypertension and diabetes among young patients admitted with AMI increased over time as well.
Abstract: Background: Sex differences are known to exist in the management of older patients presenting with acute myocardial infarction (AMI). Few studies have examined the incidence and risk factors of AMI...
331 citations
TL;DR: The application of machine learning models in the design, synthesis and characterisation of molecules at different stages in the drug discovery and development process has considerable implications for developing future therapies and their targeting.
Abstract: A variety of machine learning methods such as naive Bayesian, support vector machines and more recently deep neural networks are demonstrating their utility for drug discovery and development. These leverage the generally bigger datasets created from high-throughput screening data and allow prediction of bioactivities for targets and molecular properties with increased levels of accuracy. We have only just begun to exploit the potential of these techniques but they may already be fundamentally changing the research process for identifying new molecules and/or repurposing old drugs. The integrated application of such machine learning models for end-to-end (E2E) application is broadly relevant and has considerable implications for developing future therapies and their targeting. This Perspective describes the application of machine learning models in the design, synthesis and characterisation of molecules at different stages in the drug discovery and development process.
299 citations
TL;DR: Given the large number of OPFRs in use, manufacturers can move towards healthier and safer products by developing innovative ways to reduce fire hazard for electronics enclosures, upholstered furniture, building materials and other consumer products without adding flame retardant chemicals.
Abstract: As the use of polybrominated diphenyl ethers (PBDEs), and the entire class of organohalogen flame retardants, is declining, the use of organophosphate esters flame retardants (OPFRs) is increasing. In this paper, we ask whether OPFRs are a better choice than PBDEs. To address this question, we compared OPFRs with PBDEs for a wide range of properties. OPFRs exposure is ubiquitous in people and in outdoor and indoor environments, and are now often found at higher levels compared to PBDE peak exposure levels. Furthermore, data from toxicity testing, epidemiological studies, and risk assessments all suggest that there are health concerns at current exposure levels for both halogenated and non-halogenated OPFRs. Obtaining the scientific evidence needed for regulation of OPFRs can take many years. Given the large number of OPFRs in use, manufacturers can move towards healthier and safer products by developing innovative ways to reduce fire hazard for electronics enclosures, upholstered furniture, building materials and other consumer products without adding flame retardant chemicals.
270 citations
TL;DR: In this article, the authors investigate the causes of deforestation in Indonesia, a country with one of the highest rates of primary natural forest loss in the tropics, annually between 2001 and 2016.
Abstract: We investigate the causes of deforestation in Indonesia, a country with one of the highest rates of primary natural forest loss in the tropics, annually between 2001 and 2016. We use high spatial resolution imagery made available on Google Earth to characterize the land cover types following a random selection of deforestation events, drawn from the Global Forest Change dataset. Notorious in the region, large-scale oil palm and timber plantations together contributed more than two-fifths of nationwide deforestation over our study period, with a peak in late aughts followed by a notable decline up to 2016. Conversion of forests to grasslands, which comprised an average of one-fifth of national deforestation, rose sharply in dominance in years following periods of considerable fire activity, particularly in 2016. Small-scale agriculture and small-scale plantations also contributed one-fifth of nationwide forest loss and were the dominant drivers of loss outside the major islands of Indonesia. Although relatively small contributors to total deforestation, logging roads were responsible for a declining share of deforestation, and mining activities were responsible for an increasing share, over the study period. Direct drivers of deforestation in Indonesia are thus spatially and temporally dynamic, suggesting the need for forest conservation policy responses tailored at the subnational level, and new methods for monitoring the causes of deforestation over time.
209 citations
TL;DR: The data indicate that a transient hybrid state precedes uniparental chromosome elimination in maize HI, and edited plants could be used in trait testing and directly integrated into commercial variety development.
Abstract: Genome editing using CRISPR-Cas9 works efficiently in plant cells1, but delivery of genome-editing machinery into the vast majority of crop varieties is not possible using established methods2. We co-opted the aberrant reproductive process of haploid induction (HI)3-6 to induce edits in nascent seeds of diverse monocot and dicot species. Our method, named HI-Edit, enables direct genomic modification of commercial crop varieties. HI-Edit was tested in field and sweet corn using a native haploid-inducer line4 and extended to dicots using an engineered CENH3 HI system7. We also recovered edited wheat embryos using Cas9 delivered by maize pollen. Our data indicate that a transient hybrid state precedes uniparental chromosome elimination in maize HI. Edited haploid plants lack both the haploid-inducer parental DNA and the editing machinery. Therefore, edited plants could be used in trait testing and directly integrated into commercial variety development.
205 citations
TL;DR: Structural-based design yielded the potent, highly selective, and orally bioavailable small-molecule inhibitor VTP50469, which displaced Menin from protein complexes and inhibited chromatin occupancy of MLL at select genes.
197 citations
TL;DR: The long‐term safety and efficacy of mepolizumab in patients with severe eosinophilic asthma are supported, and the immunogenicity profile was consistent with previous studies.
Abstract: Background Mepolizumab has demonstrated favorable safety and efficacy profiles in placebo-controlled trials of 12 months' duration or less; however, long-term data are lacking. Objective We sought to evaluate the long-term safety and efficacy of mepolizumab in patients with severe eosinophilic asthma (SEA). Methods COLUMBA (Open-label Long Term Extension Safety Study of Mepolizumab in Asthmatic Subjects, NCT01691859 ) was an open-label extension study in patients with SEA previously enrolled in DREAM (Dose Ranging Efficacy And Safety With Mepolizumab in Severe Asthma, NCT01000506 ). Patients received 100 mg of subcutaneous mepolizumab every 4 weeks plus standard of care until a protocol-defined stopping criterion was met. Safety end points included frequency of adverse events (AEs), serious AEs, and AEs of special interest. Efficacy end points included annualized exacerbation rates, changes from baseline in Asthma Control Questionnaire 5 scores, and blood eosinophil counts. Immunogenicity was also assessed. Results Overall, 347 patients were enrolled for an average of 3.5 years (maximum, 4.5 years; total exposure, 1201 patient-years). On-treatment AEs were reported in 94% of patients (exposure-adjusted rate, 3688 events/1000 patient-years). The most frequently reported on-treatment AEs were respiratory tract infection, headache, bronchitis, and asthma worsening. Seventy-nine (23%) patients experienced 1 or more on-treatment serious AEs; there were 6 deaths, none of which were assessed as related to mepolizumab. For patients with 156 weeks or greater enrollment, the exacerbation rate was 0.74 events/y (weeks 0–156), a 56% reduction from the off-treatment period between DREAM and COLUMBA. For all patients, at the first postbaseline assessment, the mean Asthma Control Questionnaire 5 score was reduced by 0.47 points, and blood eosinophil counts were reduced by 78%, with similar improvements maintained throughout the study. The immunogenicity profile (8% anti-drug antibodies) was consistent with previous studies. Conclusion These data support the long-term safety and efficacy of mepolizumab in patients with SEA.
179 citations
TL;DR: Using FTS and receiving a positive test result was associated with changes in drug use behavior and perceptions of overdose safety and may represent an effective addition to current overdose prevention efforts when included with other evidence-based strategies.
168 citations
TL;DR: This indirect treatment comparison (ITC) of the licensed doses suggests that mepolizumab was associated with significantly greater improvements in clinically significant exacerbations and asthma control compared with resl Lizumab or benralIZumab in patients with similar blood eosinophil counts.
Abstract: Background Three anti–IL-5 pathway–directed therapies are approved for use in patients with severe eosinophilic asthma (SEA); however, no head-to-head comparison data are available. Objective We sought to compare the efficacy of licensed doses of mepolizumab, benralizumab, and reslizumab in patients with SEA, according to baseline blood eosinophil counts. Methods This indirect treatment comparison (ITC) used data from a Cochrane review and independent searches. Eligible studies were randomized controlled trials in patients aged 12 years or greater with SEA. End points included annualized rate of clinically significant exacerbations and change from baseline in Asthma Control Questionnaire score and FEV1. An ITC was performed in patients with Asthma Control Questionnaire scores of 1.5 or greater and stratified by baseline blood eosinophil count. Results Eleven studies were included. All treatments significantly reduced the rate of clinically significant exacerbations and improved asthma control versus placebo in all blood eosinophil count subgroups. Mepolizumab reduced clinically significant exacerbations by 34% to 45% versus benralizumab across subgroups (rate ratio ≥400 cells/μL: 0.55 [95% CI, 0.35-0.87]; ≥300 cells/μL: 0.61 [95% CI, 0.37-0.99]; and ≥150 cells/μL: 0.66 [95% CI, 0.49-0.89]; all P Conclusions This ITC of the licensed doses suggests that mepolizumab was associated with significantly greater improvements in clinically significant exacerbations and asthma control compared with reslizumab or benralizumab in patients with similar blood eosinophil counts.
161 citations
TL;DR: This study measured 17 PFAS in source and treated water from 25 drinking water treatment plants (DWTPs) as part of a broader study of CECs in drinking water across the United States.
University of Cincinnati1, Tel Aviv University2, Harvard University3, University of Haifa4, Technion – Israel Institute of Technology5, University of Pittsburgh6, University of California, San Diego7, Georgia Institute of Technology8, University of North Carolina at Chapel Hill9, Women & Children's Hospital of Buffalo10, Emory University11, Riley Hospital for Children12, Boston Children's Hospital13, Nationwide Children's Hospital14, University of Pennsylvania15, University of California, San Francisco16, University of Toronto17, University of Texas Southwestern Medical Center18, Medical College of Wisconsin19, Research Triangle Park20
TL;DR: In this article, the authors used RNAseq to define pre-treatment rectal gene expression, and fecal microbiota profiles, in 206 pediatric ulcerative colitis patients receiving standardised therapy.
Abstract: Molecular mechanisms driving disease course and response to therapy in ulcerative colitis (UC) are not well understood. Here, we use RNAseq to define pre-treatment rectal gene expression, and fecal microbiota profiles, in 206 pediatric UC patients receiving standardised therapy. We validate our key findings in adult and paediatric UC cohorts of 408 participants. We observe a marked suppression of mitochondrial genes and function across cohorts in active UC, and that increasing disease severity is notable for enrichment of adenoma/adenocarcinoma and innate immune genes. A subset of severity genes improves prediction of corticosteroid-induced remission in the discovery cohort; this gene signature is also associated with response to anti-TNFα and anti-α4β7 integrin in adults. The severity and therapeutic response gene signatures were in turn associated with shifts in microbes previously implicated in mucosal homeostasis. Our data provide insights into UC pathogenesis, and may prioritise future therapies for nonresponders to current approaches.
TL;DR: The Peak Pruritus Numerical Rating Scale (NRS) was developed and validated as a single‐item, patient‐reported outcome (PRO) of itch severity.
Abstract: Background Moderate-to-severe atopic dermatitis (AD) is a chronic disease characterized by intense, persistent and debilitating itch, resulting in sleep deprivation, signs of anxiety and depression, impaired quality of life and reduced productivity. The Peak Pruritus Numerical Rating Scale (NRS) was developed and validated as a single-item, patient-reported outcome (PRO) of itch severity. Objectives To describe the content validity and psychometric assessment (test-retest reliability, construct validity, known-groups validity, sensitivity to change) of the Peak Pruritus NRS, and to derive empirically a responder definition to identify adults with a meaningful change in itch. Methods Content validity was assessed through in-depth patient interviews. Psychometric assessments used data from phase IIb and phase III dupilumab clinical trials and included test-retest reliability, construct validity, known-groups validity and sensitivity to change in patients with moderate-to-severe AD. Results Interview participants indicated that the Peak Pruritus NRS was a relevant, clear and comprehensive assessment of itch severity. Peak Pruritus NRS scores showed large, positive correlations with existing PRO measures of itch, and weak or moderate correlations with clinician-reported measures assessing objective signs of AD. Peak Pruritus NRS score improvements were highly correlated with improvements in other itch PROs, and moderately correlated with improvements in clinician-reported measures assessing objective signs of AD. The most appropriate threshold for defining a clinically relevant, within-person response was ≥ 2-4-point change in the Peak Pruritus NRS. Conclusions The Peak Pruritus NRS is a well-defined, reliable, sensitive and valid scale for evaluating worst itch intensity in adults with moderate-to-severe AD.
Harvard University1, Ragon Institute of MGH, MIT and Harvard2, Beth Israel Deaconess Medical Center3, University of Pennsylvania4, Rockefeller University5, University of KwaZulu-Natal6, University of North Carolina at Chapel Hill7, University of Oxford8, Merck & Co.9, Treatment Action Group10, Brigham and Women's Hospital11, ViiV Healthcare12, Catalan Institution for Research and Advanced Studies13, University of Vic14, Wistar Institute15, Cornell University16, Research Triangle Park17, University of Minnesota18, Center for Drug Evaluation and Research19, Aarhus University20, Yale University21, University of the Witwatersrand22, University of Pittsburgh23, University of California, San Francisco24, Howard Hughes Medical Institute25
TL;DR: This Review presents the major points of discussion and consensus views achieved with the goal of informing the conduct of ATIs to maximise the knowledge gained and minimise the risk to participants in clinical HIV research.
TL;DR: Comparisons of life history traits between solitary bees (SB) and honey bees (HB) are compared to identify potential SB model species for risk assessment and evaluate whether current HB risk assessment schemes cover routes and levels of exposure of SB.
Abstract: Current pesticide risk assessment for bees relies on a single (social) species, the western honey bee, Apis mellifera L. (Hymenoptera: Apidae). However, most of the >20,000 bee species worldwide are solitary. Differences in life history traits between solitary bees (SB) and honey bees (HB) are likely to determine differences in routes and levels of pesticide exposure. The objectives of this review are to: 1) compare SB and HB life history traits relevant for risk assessment; 2) summarize current knowledge about levels of pesticide exposure for SB and HB; 3) identify knowledge gaps and research needs; 4) evaluate whether current HB risk assessment schemes cover routes and levels of exposure of SB; and 5) identify potential SB model species for risk assessment. Most SB exposure routes seem well covered by current HB risk assessment schemes. Exceptions to this are exposure routes related to nesting substrates and nesting materials used by SB. Exposure via soil is of particular concern because most SB species nest underground. Six SB species (Hymenoptera: Megachilidae - Osmia bicornis L., O. cornifrons Radoszkowski, O. cornuta Latreille, O. lignaria Say, Megachile rotundata F., and Halictidae - Nomia melanderi Cockerell) are commercially available and could be used in risk assessment. Of these, only N. melanderi nests underground, and the rest are cavity-nesters. However, the three Osmia species collect soil to build their nests. Life history traits of cavity-nesting species make them particularly suitable for semifield and, to a lesser extent, field tests. Future studies should address basic biology, rearing methods and levels of exposure of ground-nesting SB species.
TL;DR: In patients with non-cystic fibrosis bronchiectasis and chronic P aeruginosa lung infection requiring antibiotic therapy in the preceding year, ARD-3150 led to a significantly longer median time to first pulmonary exacerbation compared with placebo in OR BIT-4, but not in ORBIT-3 or the pooled analysis.
TL;DR: Application of the total oxidizable precursor (TOP) assay in its proposed enhanced form revealed high levels of PFEAs, the presence of precursors that form perfluoroalkyl carboxylic acids, and the absence of precursor that form P FEAs in surface water impacted by PFAS-containing wastewater discharges.
Abstract: Per- and polyfluoroalkyl substances (PFASs) are widely used anthropogenic chemicals. The PFAS class includes almost 5000 registered compounds, but analytical methods are lacking for most PFASs. The total oxidizable precursor (TOP) assay was developed to indirectly quantify unknown PFASs that are precursors to commonly measured perfluoroalkyl acids. To understand the behavior of recently identified per- and polyfluoroalkyl ether acids (PFEAs), including fluorinated replacements and manufacturing byproducts, we determined the fate of 15 PFEAs in the TOP assay. Ten perfluoroalkyl ether acids and a chlorinated polyfluoroalkyl ether acid (F-53B) were stable in the TOP assay and represent terminal products that are likely as persistent as historically used PFASs. Adding perfluoroalkyl ether acids and F-53B to the target analyte list for the TOP assay is recommended to capture a higher percentage of the total PFAS concentration in environmental samples. In contrast, polyfluoroalkyl ether acids with a -O-CFH- moiety were oxidized, typically to products that could not be identified by liquid chromatography and high-resolution mass spectrometry. Application of the TOP assay in its proposed enhanced form revealed high levels of PFEAs, the presence of precursors that form perfluoroalkyl carboxylic acids, and the absence of precursors that form PFEAs in surface water impacted by PFAS-containing wastewater discharges.
TL;DR: A new version (version 2) of the genomic dose-response analysis software, BMDExpress, has been created, which addresses the increasing use of transcriptomic dose- response data in toxicology, drug design, risk assessment and translational research.
Abstract: Summary A new version (version 2) of the genomic dose-response analysis software, BMDExpress, has been created. The software addresses the increasing use of transcriptomic dose-response data in toxicology, drug design, risk assessment and translational research. In this new version, we have implemented additional statistical filtering options (e.g. Williams' trend test), curve fitting models, Linux and Macintosh compatibility and support for additional transcriptomic platforms with up-to-date gene annotations. Furthermore, we have implemented extensive data visualizations, on-the-fly data filtering, and a batch-wise analysis workflow. We have also significantly re-engineered the code base to reflect contemporary software engineering practices and streamline future development. The first version of BMDExpress was developed in 2007 to meet an unmet demand for easy-to-use transcriptomic dose-response analysis software. Since its original release, however, transcriptomic platforms, technologies, pathway annotations and quantitative methods for data analysis have undergone a large change necessitating a significant re-development of BMDExpress. To that end, as of 2016, the National Toxicology Program assumed stewardship of BMDExpress. The result is a modernized and updated BMDExpress 2 that addresses the needs of the growing toxicogenomics user community. Availability and implementation BMDExpress 2 is available at https://github.com/auerbachs/BMDExpress-2/releases. Supplementary information Supplementary data are available at Bioinformatics online.
TL;DR: A rigorous review of published studies that have used the Soil and Water Assessment Tool for pesticide modeling pointed out a new insight of pesticide fate and transport modeling at watershed level, which should be seen as steps leading to the direction for model development, as well as better addressing management concerns of local stakeholders for model implementation.
TL;DR: When administered with two NRTIs, dolutegravir was superior to ritonavir-boosted lopinavir at 48 weeks and can be considered a suitable option for second-line treatment.
Abstract: Summary Background Doubts exist regarding optimal second-line treatment options for HIV-1-infected patients in resource-limited settings. We assessed safety and efficacy of dolutegravir compared with ritonavir-boosted lopinavir, plus two nucleoside reverse transcriptase inhibitors (NRTIs) in adults in whom previous first-line antiretroviral therapy with a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two NRTIs has failed. Methods DAWNING is a phase 3b, open-label, parallel-group, non-inferiority, active-controlled trial done at 58 sites in 13 countries. Eligible adults were aged at least 18 years and, during at least 6 months of treatment with a first-line treatment containing an NNRTI and two NRTIs, had virological failure (confirmed HIV-1 RNA ≥400 copies per mL). Participants were randomly assigned by a central randomisation system to receive oral dolutegravir (50 mg once daily) or ritonavir-boosted lopinavir (800 mg lopinavir plus 200 mg ritonavir once daily or 400 mg plus 100 mg twice daily), plus two investigator-selected NRTIs (at least one fully active based on resistance testing at screening). The primary outcome was the proportion of participants achieving viral suppression (defined as plasma HIV-1 RNA Findings Between Dec 11, 2014, and June 27, 2016, 968 adults were screened and 627 were randomly assigned to the dolutegravir group (n=312) or the ritonavir-boosted lopinavir group (n=315). Three patients in the ritonavir-boosted lopinavir group did not receive study medication and so 624 were included in the ITT-E population. At week 48, 261 (84%) of 312 participants in the dolutegravir group achieved viral suppression compared with 219 (70%) of 312 in the ritonavir-boosted lopinavir group (adjusted difference 13·8%; 95% CI 7·3–20·3). Non-inferiority was achieved on the basis of the 95% CI of the adjusted treatment difference having a lower bound greater than −12% (prespecified non-inferiority margin). Because the lower bound of the 95% CI is greater than zero (7·3%), superiority of dolutegravir was also concluded (p vs 11 [4%] of 314 with dolutegravir), mainly driven by gastrointestinal disorders. Interpretation When administered with two NRTIs, dolutegravir was superior to ritonavir-boosted lopinavir at 48 weeks and can be considered a suitable option for second-line treatment. Funding ViiV Healthcare.
TL;DR: This review will summarize new information related to the developmental biology of uterine glands and discuss novel perspectives on their functional roles in pregnancy establishment and success.
Abstract: All mammalian uteri contain glands in the endometrium that develop only or primarily after birth. Gland development or adenogenesis in the postnatal uterus is intrinsically regulated by proliferation, cell-cell interactions, growth factors and their inhibitors, as well as transcription factors, including forkhead box A2 (FOXA2) and estrogen receptor α (ESR1). Extrinsic factors regulating adenogenesis originate from other organs, including the ovary, pituitary, and mammary gland. The infertility and recurrent pregnancy loss observed in uterine gland knockout sheep and mouse models support a primary role for secretions and products of the glands in pregnancy success. Recent studies in mice revealed that uterine glandular epithelia govern postimplantation pregnancy establishment through effects on stromal cell decidualization and placental development. In humans, uterine glands and, by inference, their secretions and products are hypothesized to be critical for blastocyst survival and implantation as well as embryo and placental development during the first trimester before the onset of fetal-maternal circulation. A variety of hormones and other factors from the ovary, placenta, and stromal cells impact secretory function of the uterine glands during pregnancy. This review summarizes new information related to the developmental biology of uterine glands and discusses novel perspectives on their functional roles in pregnancy establishment and success.
TL;DR: Overall, the epidemiologic literature appears to support an association between benzene and childhood leukemia risk, with no indication of any threshold effect.
Abstract: Background: A causal link between outdoor air pollution and childhood leukemia has been proposed, but some older studies suffer from methodological drawbacks. To the best of our knowledge, no syste...
TL;DR: Tapinarof cream is efficacious and well tolerated in adolescent and adult patients with AD and the rate of treatment‐emergent adverse events was higher with tapinarof than with vehicle, and the events were mild to moderate in intensity.
Abstract: Background Safe and efficacious topical treatments are needed for atopic dermatitis (AD). Objective We assessed the safety and efficacy of tapinarof cream (2 concentrations and 2 application frequencies) in patients with AD. Methods A double-blind, vehicle-controlled, randomized, 6-arm trial (1:1:1:1:1:1) in patients age 12 to 65 years, with body surface area involvement of at least 5% to 35% and an Investigator's Global Assessment score of 3 or higher (moderate to severe) at baseline. Primary end points included an Investigator's Global Assessment score of clear or almost clear (0 or 1) and a minimum 2-grade improvement (treatment success) at week 12. Secondary analyses included a 75% or greater improvement in Eczema Area and Severity Index score, reduction of numeric rating scale (NRS) score for itch from baseline, and other prespecified end points. Results The rates of treatment success with tapinarof cream at week 12 were 53% (a concentration of 1% twice daily), 46% (a concentration of 1% once daily), 37% (a concentration of 0.5% twice daily), 34% (0.5% once daily), 24% (vehicle twice daily), and 28% (vehicle once daily). The rate with a concentration of 1% twice daily (53%) was statistically significantly higher than the rate with vehicle twice daily (24%). Treatment success was maintained for 4 weeks after the end of tapinarof treatment. The rate of treatment-emergent adverse events was higher with tapinarof (93 of 165 [56%]) than with vehicle (34 of 82 [41%]), and the events were mild to moderate in intensity. Limitations Large confirmation trials are needed. Conclusions Tapinarof cream is efficacious and well tolerated in adolescent and adult patients with AD.
TL;DR: To assess test–retest reliability for PRO measures, the two-way mixed-effect analysis of variance model with interaction for the absolute agreement between single scores is recommended.
Abstract: Purpose
The US Food and Drug Administration (FDA) 2009 guidance for industry on patient-reported outcome (PRO) measures describes how the Agency evaluates the psychometric properties of measures intended to support medical product labeling claims. An important psychometric property is test–retest reliability. The guidance lists intraclass correlation coefficients (ICCs) and the assessment time period as key considerations for test–retest reliability evaluations. However, the guidance does not provide recommendations regarding ICC computation, nor is there consensus within the measurement literature regarding the most appropriate ICC formula for test–retest reliability assessment. This absence of consensus emerged as an issue within Critical Path Institute’s PRO Consortium. The purpose of this project was to generate thoughtful and informed recommendations regarding the most appropriate ICC formula for assessing a PRO measure’s test–retest reliability.
University of North Carolina at Chapel Hill1, University of Minnesota2, University of Michigan3, University of California, Berkeley4, Federal University of Amazonas5, Centre national de la recherche scientifique6, University of Washington7, National Institute of Amazonian Research8, Harvard University9, Cooperative Institute for Research in Environmental Sciences10, Electric Power Research Institute11, Aarhus University12, Research Triangle Park13
TL;DR: It is demonstrated that changes in SO2 emissions, especially in isoprene-dominated environments, will significantly alter biogenic SOA physicochemical properties, and IEPOX/Sulfinorg will play an important role in understanding the historical climate and determining future impacts of biogenic SoA on the global climate and air quality.
Abstract: Acid-driven multiphase chemistry of isoprene epoxydiols (IEPOX), key isoprene oxidation products, with inorganic sulfate aerosol yields substantial amounts of secondary organic aerosol (SOA) throug...
University of North Carolina at Chapel Hill1, University of Colorado Hospital2, University of Warmia and Mazury in Olsztyn3, University of Oklahoma4, University of Tennessee Medical Center5, Gulf Coast Regional Blood Center6, University of New Mexico7, Emory University8, University of Colorado Boulder9, Research Triangle Park10, Dartmouth–Hitchcock Medical Center11
TL;DR: Tilaciclib demonstrated an improvement in the patient’s tolerability of chemotherapy as shown by myelopreservation across multiple hematopoietic lineages resulting in fewer supportive care interventions and dose reductions, improved safety profile, and no detriment to antitumor efficacy.
TL;DR: This approach is an improvement in estimating future global food security by simultaneously projecting climate change effects on crop productivity and changes in nutrient content under increased concentrations of CO2, which accounts for a much larger effect on nutrient availability than CO2 fertilisation.
TL;DR: Exposure to PM2.5, on all days and locations, was associated with increased hospitalizations on smoke and non-smoke days using modeled exposure metrics, whereas risk for asthma-related hospitalizations was higher during smoke days.
Abstract: Background: The effects of exposure to fine particulate matter (PM2.5) during wildland fires are not well understood in comparison with PM2.5 exposures from other sources. Objectives: We examined t...
TL;DR: The therapeutic potential of GDF15 as a pharmacological agent in obesity and other metabolic diseases was discussed and GFRAL, a member of the glial-derived neurotropic factor receptor α family, has only been recently identified as a receptor for mature GDF 15.