Stakeholders met to address persistent challenges facing the development of therapeutics for polyarticular juvenile idiopathic arthritis (pJIA), which result in fewer approved therapies for children ...with pJIA than adults with rheumatoid arthritis (RA) and long lag times from adult RA approval to pediatric labeling. Ensuring that new medications are authorized in a timely manner to meet the needs of JIA patients worldwide is critically important to multiple stakeholders.
The Food and Drug Administration in collaboration with the University of Maryland Center for Regulatory Science and Innovation held a public workshop entitled "Accelerating Drug Development for pJIA" on October 2, 2019, to address challenges surrounding access to new medications for children and adolescents with pJIA. Regulatory, academic, and industry stakeholders, as well as patient representatives, participated in the workshop, which consisted of 4 sessions, including panel discussions.
The workshop facilitated broad public discussion of challenges facing the development of pJIA therapeutics, highlighting areas of need and outlining opportunities to expedite development, while underscoring the necessity of close collaboration between all stakeholders, including patients and families.
This report summarizes key aspects of the workshop, including the appropriate application of innovative approaches to the development of pJIA therapeutics, including extrapolation, to address current challenges and provide timely access to newer safe and effective treatments. Long-term safety assessment is of pressing concern to stakeholders and cannot be fully extrapolated from adult studies but requires consistent postmarketing long-term follow-up.
The research was conducted on 18 samples of RYO tobacco. The density (CFU/g a.d.s.) of three heterotrophic groups of microorganisms and some physical-chemical indicators were determined. The analyses ...were performed according to classic methods. Quantitative and qualitative changes at the microbiome as a result of disruption of homeostasis in microbial communities and development of secondary succession in the direction of intensive mineralization processes were found. Statistically significant correlation dependences with the physical-chemical parameters were registered. In addition to a potential risk in term of sanitary-hygiene and health aspects, the changes also have a negative impact on the consumer qualities of tobacco blends.
ABSTRACT
The chemical abundances of exoplanet atmospheres may provide valuable information about the bulk compositions, formation pathways, and evolutionary histories of planets. Exoplanets with ...large, relatively cloud-free atmospheres, and which orbit bright stars provide the best opportunities for accurate abundance measurements. For this reason, we measured the transmission spectrum of the bright (V ∼ 10.2), large (1.37 RJ), sub-Saturn mass (0.19 MJ) exoplanet WASP-127b across the near-UV to near-infrared wavelength range (0.3–5 μm), using the Hubble and Spitzer Space Telescopes. Our results show a feature-rich transmission spectrum, with absorption from Na, H2O, and CO2, and wavelength-dependent scattering from small-particle condensates. We ran two types of atmospheric retrieval models: one enforcing chemical equilibrium, and the other which fit the abundances freely. Our retrieved abundances at chemical equilibrium for Na, O, and C are all supersolar, with abundances relative to solar values of 9$^{+15}_{-6}$, 16$^{+7}_{-5}$, and 26$^{+12}_{-9}$, respectively. Despite giving conflicting C/O ratios, both retrievals gave supersolar CO2 volume mixing ratios, which adds to the likelihood that WASP-127b’s bulk metallicity is supersolar, since CO2 abundance is highly sensitive to atmospheric metallicity. We detect water at a significance of 13.7σ. Our detection of Na is in agreement with previous ground-based detections, though we find a much lower abundance, and we also do not find evidence for Li or K despite increased sensitivity. In the future, spectroscopy with James Webb Space Telescope will be able to constrain WASP-127b’s C/O ratio, and may reveal the formation history of this metal-enriched, highly observable exoplanet.
The current investigation includes technological assessment and interpretation of the profile of tobaccos, tobacco derivatives and smoking products illegally distributed in Bulgaria, as officially ...provided for expertise in the Tobacco and Tobacco Products Institute (TTPI) by external contractors (legitimate state structures) in 2021. The physical and chemical properties of the tobacco objects, depending on their nature, were determined according to standardized methods. The biggest share in the analyses (139 in total) took the determination of tobacco cut width (39%) and particle size fractionation (37%), which supported the observation that the illicit tobacco market in Bulgaria is recently dominated by cut tobacco for hand-rolled cigarettes. In the cut tobacco predominated long and medium-sized strands, but in widely varying proportions (42.27-81.78% and 9.98-38.46%, respectively), with cut width in 0.59-1.06 mm range. The sieve analysis and the expert examination of the tobacco derivatives revealed that they were undoubtedly technological tobacco waste, and, respectively, that accentuated data must be communicated to consumers about the risks associated with the smoking of such tobacco articles. It was found that all illicitly traded fine-cut tobacco blends produced considerably higher tar (12.25-16.05 mg/cig) and CO (12.74-16.94 mg/cig) emissions than the limits set for conventional cigarettes.
The aim of the current study was to assess the quality level of Oriental tobaccos from the market sector of the “Basmi” variety group from different production areas in Bulgaria. Tobaccos from ...Krumovgrad and Greek Basma ecotypes (varieties “Krumovgrad 90”, “Krumovgrad 58”, “Krumovgrad 78”, and “Basma”, respectively) were investigated, all farmer-produced (2019 crop year) in seven tobacco regions. The investigation followed a procedure validated for monitoring the quality of Bulgarian tobaccos, incorporating four evaluation steps – chemical indices of tobacco and tobacco smoke, expert and smoking assessment, and final rating by a complex quality index. Statistically significant differences were observed between the compared tobaccos (variety and region based) within the two ecotypes. For Krumovgrad ecotype, the final rating of the compared tobaccos revealed the best complex quality indicators in varieties “Krumovgrad 78” from Kardzhali (micro-region Patitza), “Krumovgrad 58” from Haskovo-Harmanli (Stambolovo) and “Krumovgrad 58” from Ivaylovgrad (Belopoltzi). With the best quality level within ecotype Basma were the tobaccos produced in Svilengrad (micro-region Raykova mogila) and Momchilgrad (Chorbadzhiysko) regions. The results from the study substantiate the annual monitoring of the quality level of Bulgarian Oriental tobaccos and provide data, which have potential importance for the national tobacco sector.
In this work, a classical problem of the digital sequence design, or more precisely, finding binary sequences with optimal peak sidelobe level (PSL), is revisited. By combining some of our previous ...works, together with some mathematical insights, few hybrid heuristic algorithms were created. During our experiments, and by using the aforementioned algorithms, we were able to find PSL-optimal binary sequences for all those lengths, which were previously found during exhaustive searches by various papers throughout the literature. Then, by using a general-purpose computer, we further demonstrate the effectiveness of the proposed algorithms by revealing binary sequences with lengths between 106 and 300, the majority of which possess record-breaking PSL values. Then, by using some well-known algebraic constructions, we outline few strategies for finding highly competitive binary sequences, which could be efficiently optimized, in terms of PSL, by the proposed algorithms.
To summarize proceedings of a workshop convened to discuss the current state of science in the disease of osteoarthritis (OA), identify the knowledge gaps, and examine the developmental and ...regulatory challenges in bringing these products to market.
Summary of the one-day workshop held virtually on June 22nd, 2021.
Speakers selected by the Planning Committee presented data on the current approach to assessment of OA therapies, biomarkers in OA drug development, and the assessment of disease progression and long-term benefit.
Demonstrated by numerous failed clinical trials, OA is a challenging disease for which to develop therapeutics. The challenge is magnified by the slow time of onset of disease and the need for clinical trials of long duration and/or large sample size to demonstrate the effect of an intervention. The OA science community, including academia, pharmaceutical companies, regulatory agencies, and patient communities, must continue to develop and test better clinical endpoints that meaningfully reflect disease modification related to long-term patient benefit.
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