There have been a many publications and much discussion about green metrics. While many have been proposed, The American Chemical Society Green Chemistry Institute’s Pharmaceutical Roundtable has ...chosen process mass intensity (PMI) as the key, high-level metric for evaluating and benchmarking progress towards more sustainable manufacturing. This paper provides the philosophical and technical arguments on why PMI was chosen above other related metrics such as E factor or atom economy.
We report on the expected sensitivity of dedicated scintillator-based detectors at the LHC for elementary particles with charges much smaller than the electron charge. The dataset provided by a ...prototype scintillator-based detector is used to characterize the performance of the detector and provide an accurate background projection. Detector designs, including a novel slab detector configuration, are considered for the data taking period of the LHC to start in 2022 (Run 3) and for the high luminosity LHC. With the Run 3 dataset, the existence of new particles with masses between 10 MeV and 45 GeV could be excluded at 95% confidence level for charges between 0.003 e and 0.3 e, depending on their mass. With the high luminosity LHC dataset, the expected limits would reach between 10 MeV and 80 GeV for charges between 0.0018 e and 0.3 e, depending on their mass.
Cerebral palsy and postnatal steroids—Reply Hodgson, K. A.; Manley, B. J.; Cheong, J. L. Y.
Acta Paediatrica,
June 2023, 2023-06-00, 20230601, Letnik:
112, Številka:
6
Journal Article
Macrophages are abundantly detected at sites of disc herniation, however, their function in the disease progression is unclear. We aim to investigate the functions of macrophages in acute disc ...herniation using a macrophage Fas-induced apoptosis (MaFIA) transgenic mouse strain.
To transiently deplete macrophages, a dimerizer, AP20187, or vehicle solution was administered via intraperitoneal injection to MaFIA mice immediately, day 1 and 2 after annular puncture induced disc herniation. Local infiltrated tissues at disc hernia and DRGs at corresponding levels were harvested to analyze immune cells and neuroinflammation on postoperative day (POD) 6 by flow cytometry and/or immunostaining. Mouse spines were harvested to analyze structures of degenerated discs and adjacent vertebrae and to assess osteoclast activity by histology and tartrate-resistant acid phosphatase (TRAP) staining on POD 6, 13, and 20, respectively.
On POD 6, abundant macrophages were confirmed at disc hernia sites. Compared to vehicle control, AP20187 significantly reduced GFP+ cells in blood, spleen, and local inflammatory tissue. At disc hernia sites, AP20187 markedly reduced macrophages (CD11b+, F4/80+, GFP+CD11b+, CD11b+F4/80+) while increasing neutrophils and B cells. Transient macrophage depletion decreased ectopic bone formation and osteoclast activity in herniated discs and adjacent cortical bones for up to 20 days post herniation. Disc herniation elevated expressions of TNF-α, IL-6, substance P, calcitonin gene-related peptide, accompanied by increasing GFP+, CD11b+ and F4/80+ macrophages. Macrophage depletion did not attenuate these markers of neuroinflammation.
Transient depletion of macrophages altered local inflammatory response at the site of disc herniation.
Green Chemistry is the design, development, and implementation of chemical products and processes to reduce or eliminate the use and generation of substances hazardous to human health and the ...environment. It is an innovative, non-regulatory, economically driven approach toward sustainability. The unequivocal value of Green Chemistry to the business and to the environment is illustrated through industrial examples. Green Chemistry must be recognized for its ability to address sustainability at the molecular level. By designing for sustainability at this fundamental level, Green Chemistry challenges innovators to design and utilize matter and energy in a way that increases performance and value while protecting human health and the environment. The principles of Green Chemistry today need to become the core for tomorrow's chemistry, integrating sustainability into science and its innovations.
Summary
A clearer understanding of the tumor immune microenvironment (TIME) in metastatic clear cell renal cell carcinoma (ccRCC) may help to inform precision treatment strategies. We sought to ...identify clinically meaningful TIME signatures in ccRCC. We studied tumors from 39 patients with metastatic ccRCC using quantitative multiplexed immunofluorescence and relevant immune marker panels. Cell densities were analyzed in three regions of interest (ROIs): tumor core, tumor–stroma interface and stroma. Patients were stratified into low‐ and high‐marker density groups using median values as thresholds. Log‐rank and Cox regression analyses while controlling for clinical variables were used to compare survival outcomes to patterns of immune cell distributions. There were significant associations with increased macrophage (CD68+CD163+CD206+) density and poor outcomes across multiple ROIs in primary and metastatic tumors. In primary tumors, T‐bet+ T helper type 1 (Th1) cell density was highest at the tumor–stromal interface (P = 0·0021), and increased co‐expression of CD3 and T‐bet was associated with improved overall survival (P = 0·015) and survival after immunotherapy (P = 0·014). In metastatic tumor samples, decreased forkhead box protein 3 (FoxP3)+ T regulatory cell density correlated with improved survival after immunotherapy (P = 0·016). Increased macrophage markers and decreased Th1 T cell markers within the TIME correlated with poor overall survival and treatment outcomes. Immune markers such as FoxP3 showed consistent levels across the TIME, whereas others, such as T‐bet, demonstrated significant variance across the distinct ROIs. These findings suggest that TIME profiling outside the tumor core may identify clinically relevant associations for patients with metastatic ccRCC.
A better understanding of the tumor immune microenvironment may serve as a critical step in advancing precision treatment strategies. We analyzed tumors from patients with metastatic clear cell renal cell carcinoma using quantitative multiplexed immunofluorescence and relevant immune cell markers in three separate regions of interest. Our results demonstrate that patterns of immune cell spatial distribution across microenvironment compartments in primary and metastatic tumors correlate with meaningful clinical outcomes.
Nasal high-flow therapy (nHFT) is commonly used for noninvasive respiratory support in the neonatal intensive care unit. Our objective was to determine which aspects of neonatal nHFT have achieved ...adequate evidence base to support consensus among experienced clinical investigators, and to document areas lacking consensus to promote future investigations.
Prospective, modified Delphi collation of tabular queries related to specific aspects of neonatal nHFT. Seven international nHFT clinical researchers were queried regarding approaches to initiation, escalation, weaning and discontinuing nHFT. Completed tables were reviewed independently by each investigator, results clarified and discussed and areas of consensus determined.
Consensus agreement was reached for many aspects of nHFT including: need for adequate heating and humidification, need to prevent nares occlusion, maximum flow rate of 8 l min
, assessment of fraction of inspired oxygen (FiO
) and work of breathing for either flow escalation or weaning, equivalence of nHFT to nasal continuous positive airway pressure (nCPAP) for noninvasive support of infants of ⩾28 weeks with resolving respiratory distress and use of nHFT for noninvasive support of stable infants on nCPAP. There was general agreement for initial gas flow rates in the range of 4 to 6 l min
and for nHFT as primary therapy for mild respiratory distress. There was no consensus on the approach to discontinuing nHFT.
Among an experienced group of nHFT clinical researchers, there was general consensus in the approach to neonatal nHFT. Additional randomized studies are indicated to provide better evidence related to several aspects of nHFT, as well as to identify other clinical conditions where nHFT may provide safe, effective noninvasive support.
Randomised trials suggest that high-flow (HF) therapy is comparable with continuous positive airway pressure (CPAP) for postextubation respiratory support in neonates, and HF has been widely adopted ...in neonatal intensive care.
We conducted a population-based study of very preterm infants born <32 weeks' gestation within the Australian and New Zealand Neonatal Network (ANZNN) data set from 2009 to 2012, who received respiratory support with HF.
3372 very preterm infants were treated with HF. HF use in this population increased significantly from 15% in 2009 to 35% in 2012. In 2012, 53% (542/1029) of extremely preterm infants born <28 weeks' gestation received HF. 98% (3308/3372) of infants had received endotracheal ventilation or CPAP prior to receiving HF. The maximum HF gas flow was ≤8 L/min in almost all infants.
HF use in extremely preterm and very preterm infants increased significantly within the ANZNN from 2009 to 2012.
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