Deoxidation and Inclusion Control for Alloy Steel

DEOXIDATION of quality steels is directed toward the casting of sound ingots free from excessive segregation, having good rolling and forging characteristics, and containing it minimum of harmful impurity elements and inclusions. In addition, deoxidation is employed for grain size control to promote maximum toughness of the steel. These objectives are a chieved by selection of suitable charge material, slag control and initial deoxi-dation practice in the furnace, and final deoxidation practice in the ladle. Although much has been learned of the physical chemistry of the process,the art of steel-making is still in large part empirical, and successful practices are somewhat difficult to rationalize. For this reason, equilibrium relations in the iron-oxygen deoxidizer systems are important, but the kinetics of deoxidation and the sequence of operations may be more significant to the operator

Position Statement of 5 July 2022 on the Decision of the WTO Ministerial Conference on the TRIPS Agreement adopted on 17 June 2022

On 17 June 2022, after nearly one and a half years of intense debate concerning the proposal to waive IP protection in view of the COVID-19 pandemic, the Ministerial Conference of the World Trade Organization adopted a decision on the TRIPS Agreement. It has not waived any intellectual property rights as such but instead mainly clarified the application of the existing TRIPS flexibilities, in particular, regarding compulsory licensing of patents. The Position Statement shows that the Ministerial Decision makes no substantive difference in the existing international legal framework, except for lifting the limitation on the exportation of vaccines manufactured in accordance with the Decision. To the extent that the Decision can make the application of TRIPS flexibilities more expedient, it is to be welcomed. At the same time, it is argued that such facilitating effect should not be limited to, or justified by, the exceptional circumstances of the COVID-19 pandemic. More critically, it should not be restricted to COVID-19 vaccines, of which there is currently no shortage – rather, the same level of TRIPS flexibilities should apply to all medicinal products needed to overcome the COVID-19 pandemic

Strain-level resolution and pneumococcal carriage dynamics by single-molecule real-time (SMRT) sequencing of the plyNCR marker: a longitudinal study in Swiss infants

BACKGROUND Pneumococcal carriage has often been studied from a serotype perspective; however, little is known about the strain-specific carriage and inter-strain interactions. Here, we examined the strain-level carriage and co-colonization dynamics of Streptococcus pneumoniae in a Swiss birth cohort by PacBio single-molecule real-time (SMRT) sequencing of the plyNCR marker. METHODS A total of 872 nasal swab (NS) samples were included from 47 healthy infants during the first year of life. Pneumococcal carriage was determined based on the quantitative real-time polymerase chain reaction (qPCR) targeting the lytA gene. The plyNCR marker was amplified from 214 samples having lytA-based carriage for pneumococcal strain resolution. Amplicons were sequenced using SMRT technology, and sequences were analyzed with the DADA2 pipeline. In addition, pneumococcal serotypes were determined using conventional, multiplex PCR (cPCR). RESULTS PCR-based plyNCR amplification demonstrated a 94.2% sensitivity and 100% specificity for Streptococcus pneumoniae if compared to lytA qPCR. The overall carriage prevalence was 63.8%, and pneumococcal co-colonization (≥ 2 plyNCR amplicon sequence variants (ASVs)) was detected in 38/213 (17.8%) sequenced samples with the relative proportion of the least abundant strain(s) ranging from 1.1 to 48.8% (median, 17.2%; IQR, 5.8-33.4%). The median age to first acquisition was 147 days, and having ≥ 2 siblings increased the risk of acquisition. CONCLUSION The plyNCR amplicon sequencing is species-specific and enables pneumococcal strain resolution. We therefore recommend its application for longitudinal strain-level carriage studies of Streptococcus pneumoniae. Video Abstract

Strain-level resolution and pneumococcal carriage dynamics by single-molecule real-time (SMRT) sequencing of the plyNCR marker: a longitudinal study in Swiss infants.

BACKGROUND Pneumococcal carriage has often been studied from a serotype perspective; however, little is known about the strain-specific carriage and inter-strain interactions. Here, we examined the strain-level carriage and co-colonization dynamics of Streptococcus pneumoniae in a Swiss birth cohort by PacBio single-molecule real-time (SMRT) sequencing of the plyNCR marker. METHODS A total of 872 nasal swab (NS) samples were included from 47 healthy infants during the first year of life. Pneumococcal carriage was determined based on the quantitative real-time polymerase chain reaction (qPCR) targeting the lytA gene. The plyNCR marker was amplified from 214 samples having lytA-based carriage for pneumococcal strain resolution. Amplicons were sequenced using SMRT technology, and sequences were analyzed with the DADA2 pipeline. In addition, pneumococcal serotypes were determined using conventional, multiplex PCR (cPCR). RESULTS PCR-based plyNCR amplification demonstrated a 94.2% sensitivity and 100% specificity for Streptococcus pneumoniae if compared to lytA qPCR. The overall carriage prevalence was 63.8%, and pneumococcal co-colonization (≥ 2 plyNCR amplicon sequence variants (ASVs)) was detected in 38/213 (17.8%) sequenced samples with the relative proportion of the least abundant strain(s) ranging from 1.1 to 48.8% (median, 17.2%; IQR, 5.8-33.4%). The median age to first acquisition was 147 days, and having ≥ 2 siblings increased the risk of acquisition. CONCLUSION The plyNCR amplicon sequencing is species-specific and enables pneumococcal strain resolution. We therefore recommend its application for longitudinal strain-level carriage studies of Streptococcus pneumoniae. Video Abstract

Covid-19 and the Role of Intellectual Property - Position Statement of the Max Planck Institute for Innovation and Competition of 7 May 2021

In this Statement, the authors take a position on the waiver of intellectual property (IP) protection currently being considered by the members of the World Trade Organisation. The waiver was initiated by India and South Africa as a measure to enable rapid access to affordable medical products that are necessary to combat Covid-19. The initiative gained momentum after the US decided to support it. The authors do not consider this path to be expedient. The Statement presents factual and legal arguments why a comprehensive waiver of IP protection is unlikely to be a necessary and suitable measure towards the pursued objective. Overall, it argues that IP rights may so far have played an enabling and facilitating rather than hindering role in overcoming Covid-19. The global community might not be better off if IP rights are waived, neither during nor after the pandemic. There are more efficient and direct ways to supply developing countries with vaccines quickly – if the industrialised countries are willing to do their share

Probabilistic analysis of COVID-19 patients' individual length of stay in Swiss intensive care units

RATIONALE The COVID-19 pandemic induces considerable strain on intensive care unit resources. OBJECTIVES We aim to provide early predictions of individual patients' intensive care unit length of stay, which might improve resource allocation and patient care during the on-going pandemic. METHODS We developed a new semiparametric distributional index model depending on covariates which are available within 24h after intensive care unit admission. The model was trained on a large cohort of acute respiratory distress syndrome patients out of the Minimal Dataset of the Swiss Society of Intensive Care Medicine. Then, we predict individual length of stay of patients in the RISC-19-ICU registry. MEASUREMENTS The RISC-19-ICU Investigators for Switzerland collected data of 557 critically ill patients with COVID-19. MAIN RESULTS The model gives probabilistically and marginally calibrated predictions which are more informative than the empirical length of stay distribution of the training data. However, marginal calibration was worse after approximately 20 days in the whole cohort and in different subgroups. Long staying COVID-19 patients have shorter length of stay than regular acute respiratory distress syndrome patients. We found differences in LoS with respect to age categories and gender but not in regions of Switzerland with different stress of intensive care unit resources. CONCLUSION A new probabilistic model permits calibrated and informative probabilistic prediction of LoS of individual patients with COVID-19. Long staying patients could be discovered early. The model may be the basis to simulate stochastic models for bed occupation in intensive care units under different casemix scenarios

Nasopharyngeal Microbiota in Infants With Acute Otitis Media

Background. Interspecies interactions of the nasopharyngeal microbiota are likely to be involved in the pathogenesis of acute otitis media (AOM). Capturing the breadth of microbial interactions requires a detailed description of the microbiota during health and AOM. Methods. The nasopharyngeal microbiota of 163 infants with (n = 153) or without (n = 10) AOM was characterized using nasopharyngeal swabs and multiplexed pyrosequencing of 16S rRNA. Nasopharyngeal swab specimens were collected during 4 winter seasons from 2004 through 2010 for infants with AOM and during 2010 for controls. Results. Fifty-eight bacterial families were identified, of which Moraxellaceae, Streptococcaceae, and Pasteurellaceae were the most frequent. Commensal families were less prevalent in infants with AOM than in controls. In infants with AOM, prior exposure to antimicrobials and administration of the heptavalent conjugated pneumococcal polysaccharide vaccine (PCV7) were also associated with reduced prevalence of distinct commensal families (Streptococcaceae and Corynebacteriaceae). In addition, antimicrobial exposure increased the prevalence of Enterobacteriaceae and the abundance of Pasteurellaceae. Other factors, such as age, sex, day care, and a history of recurrent AOM, did not influence the microbiota. Conclusions. Infants' nasopharyngeal microbiota undergoes significant changes during AOM and after exposure to antimicrobials and PCV7, which is mainly attributable to reduced prevalence of commensal bacterial familie

Pharmacological Evidence Suggests That the Lysozyme/PACAP Receptor of \u3cem\u3eTetrahymena thermophila\u3c/em\u3e is a Polycation Receptor

Pituitary adenylate cyclase activating polypeptide (PACAP) is a peptide hormone that exists in two biologically active forms: PACAP-38 and PACAP-27. Several types of PACAP receptors have been characterized, and these have been classified into three families: the VPAC1, the VPAC2, and the PAC1 receptors. In this study, we used in vivo behavioral assays along with pharmacological inhibitors to investigate the behavior of the lysozyme/PACAP receptor in Tetrahymena. This receptor behaves like a PAC1 receptor in some respects; however, PACAP 6-38 serves as an agonist, rather than an antagonist, for this receptor. These results are consistent with the existence of a generalized polycation receptor rather than a PACAP-specific receptor