Prevention of arthritis by interleukin 10-producing B cells

In this study we have shown that activation of arthritogenic splenocytes with antigen and agonistic anti-CD40 gives raise to a B cell population that produce high levels of interleukin (IL)-10 and low levels of interferon (IFN)-{gamma}. Transfer of these B cells into DBA/1-TcR-ß-Tg mice, immunized with bovine collagen (CII) emulsified in complete Freund's adjuvant inhibited T helper type 1 differentiation, prevented arthritis development, and was also effective in ameliorating established disease. IL-10 is essential for the regulatory function of this subset of B cells, as the B cells population isolated from IL-10 knockout mice failed to mediate this protective function. Furthermore, B cells isolated from arthritogenic splenocytes treated in vitro with anti–IL-10/anti–IL-10R were unable to protect recipient mice from developing arthritis. Our results suggest a new role of a subset of B cells in controlling T cell differentiation and autoimmune disorders

Understanding and modeling unstarting phenomena in a supersonic inlet cascade

The renewed interest in supersonic turbomachinery research was driven by its potential applications in emerging fields. However, the design of supersonic inlet cascades faces significant challenges due to the inherent limitations of supersonic flows. While several studies have been published on the unstarting of supersonic intakes, there exists a major knowledge gap in the unstarting of supersonic blade rows. This paper presents the research on a novel unstarting mechanism for supersonic inlet cascades induced by the formation of a collective shock. Tailored simulations were carried out to study the coalescence of the leading-edge bow shock waves and to investigate the stability and the hysteresis of this phenomenon. Then, a reduced order model was developed and verified to estimate the limit induced by this additional unstarting mechanism. Since the accuracy of the unstarting condition relies heavily on the predicted bow shock shape, novel strategies were proposed to improve the estimate of the asymptotic slope of the bow shock and to account for large incidence angles. Furthermore, the well-known Kantrowitz criterion for the self-starting of a supersonic channel was reviewed and adapted to supersonic blade rows by considering both weak and strong oblique shock waves in the calculation of the maximum contract ratio. Then, it was demonstrated the importance of accounting for shock-induced boundary layer separation in the starting process of a supersonic machine. Finally, computational fluid dynamics simulations reveal the high sensitivity of the self-starting limit to the cascade solidity and profile shape

On the location of zeros of a polynomial with restricted coefficients

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The effect of grandmultiparity on pregnancy related complications: The Aga Khan University experience

Background: Grandmultiparity has been associated with complications for both mother and the fetus.Objective: To evaluate if grandmultiparity is a risk factor in the presence of adequate antenatal care.Setting: A tertiary care teaching hospital.Methods: It was a retrospective study conducted in the department of Obstetrics & Gynecology at The Aga Khan University Hospital in Karachi. During this period 9253 women were delivered, out of these 143 booked grandmultiparas (GMP) served as cases. The outcome of these women was compared with 430 non-grandmultiparas (NGMP). Logistic regression model was used to adjust for potential confounders.Results: Grandmultiparas had almost three times increased risk of having postpartum hemorrhage compared to NGMP group. Similarly, there were significantly low five-minute apgars in the GMPs compared to the NGMP group. Although the neonatal intensive care admissions were three times more in the GMPs but this did not reach statistical significance due to small number of cases in both groups.Conclusion: Our study indicates that grandmultiparity is a risk factor for pregnancy in this part of the world, even in the presence of reasonable antenatal care. This may be explained on the basis of the increased age of these women. Finally, we also recommend that an age-matched study needs to be undertaken in order to determine if age is an important determinant for risk factors in grandmultiparas

Patient-Reported Outcomes following Single- and Multiple-Radius Total Knee Replacement: A Randomized, Controlled Trial

Although single-radius (SR) designs of total knee replacement (TKR) have theoretical benefits, the clinical advantage conferred by such designs is unknown. The aim of this randomized, controlled study was to compare the short-term clinical outcomes of the two design rationales. A total of 105 knees were randomized to receive either a single radius (Scorpio, Stryker; SR Group) or multiple radius (AGC, Zimmer Biomet; MR group) TKR. Patient-reported outcomes (Oxford Knee Score [OKS] and Knee Society Score [KSS]) were collected at 6 weeks, 6 months, and 1 year following surgery. No knees were revised. There was no difference in primary outcomes: OKS was 39.5 (95% confidence interval [CI]: 36.9–42.1) in the SR group and 38.1 (95% CI: 36.0–40.3) in the MR group (p = 0.40). KSS was 168.4 (95% CI: 159.8–177.0) in the SR group; 159.5 (95% CI 150.5–168.5) in the MR group (p = 0.16). There was a small but statistically significant difference in the degree of change of the objective subscale of the KSS, favoring the SR design (p = 0.04), but this is of uncertain clinical relevance. The reported benefits of SR designs do not provide demonstrable functional advantages in the short term

Contributory factors in surgical incidents as delineated by a confidential reporting system

Background Confidential reporting systems play a key role in capturing information about adverse surgical events. However, the value of these systems is limited if the reports that are generated are not subjected to systematic analysis. The aim of this study was to provide the first systematic analysis of data from a novel surgical confidential reporting system to delineate contributory factors in surgical incidents and document lessons that can be learned. Methods One-hundred and forty-five patient safety incidents submitted to the UK Confidential Reporting System for Surgery over a 10-year period were analysed using an adapted version of the empirically-grounded Yorkshire Contributory Factors Framework. Results The most common factors identified as contributing to reported surgical incidents were cognitive limitations (30.09%), communication failures (16.11%) and a lack of adherence to established policies and procedures (8.81%). The analysis also revealed that adverse events were only rarely related to an isolated, single factor (20.71%) – with the majority of cases involving multiple contributory factors (79.29% of all cases had more than one contributory factor). Examination of active failures – those closest in time and space to the adverse event – pointed to frequent coupling with latent, systems-related contributory factors. Conclusions Specific patterns of errors often underlie surgical adverse events and may therefore be amenable to targeted intervention, including particular forms of training. The findings in this paper confirm the view that surgical errors tend to be multi-factorial in nature, which also necessitates a multi-disciplinary and system-wide approach to bringing about improvements

Screening of maize germplasm for Turcicum leaf blight resistance

: A study was conducted during Kharif 2012 and 2013 at Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir, Shalimar Campus Srinagar with the objective of screening sixty maize genotypes against Turcicum leaf blight caused by Exserohilum turcicum (Pass.) Leonard and Suggs. Field experiment was laid out in a randomized block design with three replications. In order to ensure establishment of infection, artificial inoculation of E. turcicum on test genotypes was made twice at 30 and 40 days after sowing with two different methods of inoculation (spraying on foliage of maize with spore suspension of pathogen @ 5x104 spores/ml at 30 DAS and by whorl drop inoculation of pathogen multiplies on sorghum grains at 40 DAS). Disease severity on test entries was scored at silk drying stage and studies revealed that two inbred lines, viz., NAI-112 and NAI-147, and one hybrid, viz., HQPM-1 were found resistant with pooled disease intensity of 4.12 per cent, 4.04 per cent and 4.38 per cent, respectively. Four inbred lines, viz., KDM 381 A, KDM 918 A, NAI-152 and NAI-167 were found susceptible with pooled disease intensity of 52.82 per cent, 51.02 per cent, 58.58 per cent and 61.33 per cent, respectively. The remaining genotypes were moderately resistant to moderately susceptible

Combined Spatially Resolved Optical Emission Imaging and Modeling Studies of Microwave-Activated H₂/Ar and H₂/Kr Plasmas Operating at Powers and Pressures Relevant for Diamond Chemical Vapor Deposition

Microwave (MW) activated H2/Ar (and H2/Kr) plasmas operating under powers and pressures relevant to diamond chemical vapor deposition have been investigated experimentally and by 2-D modeling. The experiments return spatially and wavelength resolved optical emission spectra of electronically excited H2 molecules and H and Ar­(/Kr) atoms for a range of H2/noble gas mixing ratios. The self-consistent 2-D­(r, z) modeling of different H2/Ar gas mixtures includes calculations of the MW electromagnetic fields, the plasma chemistry and electron kinetics, heat and species transfer and gas–surface interactions. Comparison with the trends revealed by the spatially resolved optical emission measurements and their variations with changes in process conditions help guide identification and refinement of the dominant plasma (and plasma emission) generation mechanisms and the more important Ar–H, Ar–H2, and H–H2 coupling reactions. Noble gas addition is shown to encourage radial expansion of the plasma, and thus to improve the uniformity of the H atom concentration and the gas temperature just above the substrate. Noble gas addition in the current experiments is also found to enhance (unwanted) sputtering of the copper base plate of the reactor; the experimentally observed increase in gas phase Cu* emission is shown to correlate with the near substrate ArH+ (and KrH+) ion concentrations returned by the modeling, rather than with the relatively more abundant H3+ (and H3O+) ions

New insights into the regulatory pathways associated with the activation of the stringent response in bacterial resistance to the PBP2-targeted antibiotics, mecillinam and OP0595/RG6080

Objectives: The diazabicyclooctane β-lactamase inhibitor OP0595 (RG6080) also acts as an antibiotic, targeting PBP2 in Enterobacteriaceae, but this activity is vulnerable to mutational resistance. We used WGS to investigate the basis of this resistance. Methods: Twenty OP0595-selected mutants, comprising four derived from each of five different Escherichia coli strains, were sequenced on Illumina HiSeq. Reads from each mutant were mapped to the assembled genome of the corresponding parent. A variant-calling file generated with Samtools was parsed to determine genetic alterations. Results: Besides OP0595, the mutants consistently showed decreased susceptibility to mecillinam, which likewise targets PBP2, and grew as stable round forms in the presence of subinhibitory concentrations of OP0595. Among the 20 mutants, 18 had alterations in genes encoding tRNA synthase and modification functions liable to induce expression of the RpoS sigma factor through activation of the stringent response or had mutations suppressing inactivators of RpoS or the stringent response signal-degrading enzyme, SpoT. TolB was inactivated in one mutant: this activates RcsBC regulation and was previously associated with mecillinam resistance. The mechanism of resistance remained unidentified in one mutant. Both the RpoS and RcsBC systems regulate genes of cell division, including ftsAQZ that can compensate for loss or inhibition of PBP2, allowing survival of the challenged bacteria as stable round forms, as seen. Conclusions: WGS identified the global stringent response signal, entailing induction of RpoS, as the main mediator of mutational resistance to OP0595 in E. coli