The presence of urea in runoff from fertilized soil could be contributing to the growth of dangerous blooms. Enzymatic urea hydrolysis is a well-known outstanding process that, when integrated with ...nanotechnology, would be much more efficient. This research provides a novel perspective on magnetic nanobiocatalysts that reduce diffusion barriers in effective urea hydrolysis. Surprisingly, the model developed with the use of a Genetic Algorithm (GA) and an Artificial Neural Network (ANN) demonstrated that the system's diffusion restrictions were reduced. In order to forecast accurate outputs using artificial intelligence (AI), a neural network with one hidden layer and 20 neurons was built utilizing multilayer feed-forward network and showed highest output (diffusion co-efficient) with least mean square error (MSE). The diffusion coefficients of free urease, urease immobilized onto porous MNs (U-aMNs), and nanobiocatalyst, i.e. urease immobilized onto surface modified MNs (U-MNβ), were 1.9 × 10−17, 12.62 × 10−16, and 15.48 × 10−16 cm2/min, respectively. These results revealed that the addition of Chitosan to the surface of MNs had a considerable impact on enzyme dispersion. The decrease in Damkohler number (Da) from 2.37 ± 0.26 for U-aMNs to 2.19 ± 0.11 for U-MNβ suggested a beneficial effect in overcoming diffusion constraints. Pseudo-first order and pseudo-second order models were used to analyze urea uptake kinetics, with the former model offering the best fit to the system, with R2 values that were much closer to unity.
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•Diffusion limitations is studied in urease immobilized magnetite nanoparticles.•Role of diffusion on the catalytic reaction is represented by Damkohler number.•Insight information on reaction rates is provided through kinetic studies.•Reduction in diffusion limitations was validated using GA-ANN.•This is a novel surface chemistry approach on the nanobiocatalyst.
Because we found significant differences in the levels of CLC and IL-17A between control and CRSsNP in ET and not in IT or UT (Fig 1; see Fig E2 in this article's Online Repository at ...www.jacionline.org), we focused our further analysis on ET. ...whether our results are applicable to the general population, or only tertiary care populations in the United States, would require further multiinstitutional studies.\n The minimal detection limit for this kit is 0.125 ng/mL.
We present the photometric calibration of the Swift Ultraviolet/Optical Telescope (UVOT) which includes: optimum photometric and background apertures, effective area curves, colour transformations, ...conversion factors for count rates to flux and the photometric zero-points (which are accurate to better than 4 per cent) for each of the seven UVOT broad-band filters. The calibration was performed with observations of standard stars and standard star fields that represent a wide range of spectral star types. The calibration results include the position-dependent uniformity, and instrument response over the 1600–8000 Å operational range. Because the UVOT is a photon-counting instrument, we also discuss the effect of coincidence loss on the calibration results. We provide practical guidelines for using the calibration in UVOT data analysis. The results presented here supersede previous calibration results.
Men who enter active surveillance because their biopsy exhibits only Gleason grade 3 (G3) frequently have higher grade tumor missed by biopsy. Thus, biomarkers are needed that, when measured on G3 ...tissue, can predict the presence of higher grade tumor in the whole prostate. We evaluated whether PTEN loss, chromosome 8q gain (MYC) and/or 8p loss (LPL) measured only on G3 cores is associated with un-sampled G4 tumor. A tissue microarray was constructed of prostatectomy tissue from patients whose prostates exhibited only Gleason score 3+3, only 3+4 or only 4+3 tumor (n=50 per group). Cores sampled only from areas of G3 were evaluated for PTEN loss by immunohistochemistry, and PTEN deletion, LPL/8p loss and MYC/8q gain by fluorescence in situ hybridization. Biomarker results were compared between Gleason score 6 vs 7 tumors using conditional logistic regression. PTEN protein loss, odds ratio=4.99, P=0.033; MYC/8q gain, odds ratio=5.36, P=0.010; and LPL/8p loss, odds ratio=3.96, P=0.003 were significantly more common in G3 cores derived from Gleason 7 vs Gleason 6 tumors. PTEN gene deletion was not statistically significant. Associations were stronger comparing Gleason 4+3 vs 6 than for Gleason 3+4 vs 6. MYC/8q gain, LPL/8p loss and PTEN protein loss measured in G3 tissue microarray cores strongly differentiate whether the core comes from a Gleason 6 or Gleason 7 tumor. If validated to predict upgrading from G3 biopsy to prostatectomy these biomarkers could reduce the likelihood of enrolling high-risk men and facilitate safe patient selection for active surveillance.
Background
Venous thromboembolism (VTE) is a major source of morbidity and mortality after ventral hernia surgery, but the risk of VTE after discharge has not been reported.
Study design
Data from ...the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) were used to investigate the risk of post-discharge VTE. Current procedural terminology (CPT) codes identified all reported patients who underwent ventral hernia repair from 2011 to 2017. We created a multivariable regression model for post-discharge VTE, using the 2011–2016 dataset to develop the model and 2017 as a validation set. The prediction model was used to create a risk calculator as a mobile application.
Results
The rate of VTE after surgery was 0.62% (878 of 141,065) with 48% occurring after discharge from the hospital. The final predictor model consisted of eight variables: age > 60 years, male sex, body mass index (BMI) ≥ 35 kg/m
2
), operative time > 2 h, concurrent panniculectomy, post-operative hospitalization > 1 day, presence of bleeding disorder, and emergency operation. The model had good calibration and discrimination (Hosmer–Lemeshow goodness-of-fit test,
p
= 0.71;
c
-statistic = 0.71). Threshold analysis showed a strategy of extended-duration thromboprophylaxis was optimized when the risk of post-discharge VTE was > 0.3%.
Conclusion
Forty-eight percent of VTEs after ventral hernia repair occur after discharge, particularly in older, male, obese patients undergoing longer and complex operations that require hospitalization > 1 day. Post-discharge thromboprophylaxis should be considered in these patients, particularly when risk of VTE exceeds 0.3%.
Abstract Background Clonal mast cell disorders are known to occur in a subset of patients with systemic reactions to Hymenoptera stings. This observation has prompted the question as to whether ...clonal mast cell disorders also occur in patients with idiopathic anaphylaxis (IA). Objective We sought to determine the prevalence of clonal mast cell disorders among patients with IA, criteria to identify those patients who require a bone marrow biopsy and whether the pathogenesis of IA involves a hyper-responsive mast cell compartment. Methods We prospectively enrolled patients with IA (≥3 episodes/yr) and who then underwent a medical evaluation that included a serum tryptase determination, allele-specific quantitative polymerase chain reaction (ASqPCR) for KIT D816V and a bone marrow examination. Mast cells were cultured from peripheral blood CD34+ cells and examined for releasibility following FcεRI aggregation. Results Clonal mast cell disease was diagnosed in 14% of patients referred with IA. ASqPCR for the KIT D816V mutation was a useful adjunct in helping identify those with systemic mastocytosis (SM) but not monoclonal mast cell activation syndrome (MMAS). A modified overall clonal prediction model was developed using clinical findings, a serum tryptase determination and ASqPCR. There was no evidence of a hyper-responsive mast cell phenotype in patients with IA. Conclusion Patients with clonal mast cell disease may present as idiopathic anaphylaxis. Distinct clinical and laboratory features may be used to select those patients more likely to have an underlying clonal mast cell disorder (MMAS or SM) and thus candidates for a bone marrow biopsy.
Objective It is generally accepted that patients who require biventricular assist device support have poorer outcomes than those requiring isolated left ventricular assist device support. However, it ...is unknown how the timing of biventricular assist device insertion affects outcomes. We hypothesized that planned biventricular assist device insertion improves survival compared with delayed conversion of left ventricular assist device support to biventricular assist device support. Methods We reviewed and compared outcomes of 266 patients undergoing left ventricular assist device or biventricular assist device placement at the University of Pennsylvania from April 1995 to June 2007. We subdivided patients receiving biventricular assist devices into planned biventricular assist device (P-BiVAD) and delayed biventricular assist device (D-BiVAD) groups based on the timing of right ventricular assist device insertion. We defined the D-BiVAD group as any failure of isolated left ventricular assist device support. Results Of 266 patients who receivd left ventricular assist devices, 99 (37%) required biventricular assist device support. We compared preoperative characteristics, successful bridging to transplantation, survival to hospital discharge, and Kaplan–Meier 1-year survival between the P-BiVAD (n = 71) and D-BiVAD (n = 28) groups. Preoperative comparison showed that patients who ultimately require biventricular support have similar preoperative status. Left ventricular assist device (n = 167) outcomes in all categories exceeded both P-BiVAD and D-BiVAD group outcomes. Furthermore, patients in the P-BiVAD group had superior survival to discharge than patients in the D-BiVAD group (51% vs 29%, P < .05). One-year and long-term Kaplan–Meier survival distribution confirmed this finding. There was also a trend toward improved bridging to transplantation in the P-BiVAD (n = 55) versus D-BiVAD (n = 22) groups (65% vs 45%, P = .10). Conclusion When patients at high risk for failure of isolated left ventricular assist device support are identified, proceeding directly to biventricular assist device implantation is advised because early institution of biventricular support results in dramatic improvement in survival.
Background Eosinophilic airway inflammation is heterogeneous in asthmatic patients. We recently described a distinct subtype of asthma defined by the expression of genes inducible by TH 2 cytokines ...in bronchial epithelium. This gene signature, which includes periostin, is present in approximately half of asthmatic patients and correlates with eosinophilic airway inflammation. However, identification of this subtype depends on invasive airway sampling, and hence noninvasive biomarkers of this phenotype are desirable. Objective We sought to identify systemic biomarkers of eosinophilic airway inflammation in asthmatic patients. Methods We measured fraction of exhaled nitric oxide (F eno ), peripheral blood eosinophil, periostin, YKL-40, and IgE levels and compared these biomarkers with airway eosinophilia in asthmatic patients. Results We collected sputum, performed bronchoscopy, and matched peripheral blood samples from 67 asthmatic patients who remained symptomatic despite maximal inhaled corticosteroid treatment (mean FEV1 , 60% of predicted value; mean Asthma Control Questionnaire ACQ score, 2.7). Serum periostin levels are significantly increased in asthmatic patients with evidence of eosinophilic airway inflammation relative to those with minimal eosinophilic airway inflammation. A logistic regression model, including sex, age, body mass index, IgE levels, blood eosinophil numbers, F eno levels, and serum periostin levels, in 59 patients with severe asthma showed that, of these indices, the serum periostin level was the single best predictor of airway eosinophilia ( P = .007). Conclusion Periostin is a systemic biomarker of airway eosinophilia in asthmatic patients and has potential utility in patient selection for emerging asthma therapeutics targeting TH 2 inflammation.
Background Despite the high prevalence and morbidity of chronic rhinosinusitis (CRS), little is known about the mechanisms that underlie its pathogenesis. Recent studies have suggested that B cells ...might play an important role in CRS. Objective We sought to thoroughly characterize B lineage cells within sinus tissues of patients with CRS and healthy control subjects and to determine whether levels of EBV-induced protein 2, which is known to play an important role in the development of B-cell responses, were increased in patients with CRS. Methods Cells isolated from sinus tissues of patients with CRS and healthy control subjects were characterized by means of flow cytometry and immunohistochemistry. Local production of antibodies was measured in tissue extracts, nasal lavage fluid, and sera by using multiplex bead arrays and ELISA. Quantitative RT-PCR, ELISA, and Western blotting were used to assess gene and protein expression from tissue extracts. Results Nasal polyps (NPs) from patients with CRS had increased levels of both B cells and plasma cells compared with uncinate tissue from healthy control subjects ( P < .05). NPs also contained significantly increased levels of several antibody isotypes compared with normal uncinate tissue ( P < .05), but no differences in circulating antibody levels were found. Interestingly, levels of EBV-induced protein 2 were also increased in NPs ( P < .05) and were positively correlated with expression of plasma cell markers (CD138 and B lymphocyte–induced maturation protein) in sinus tissue. Conclusion B cells and plasma cells are enriched in NPs, actively produce antibodies locally, and might contribute to chronic inflammation in patients with CRS. Elucidating the mechanisms that underlie this excessive local B-cell response might provide novel insights for the development of improved therapeutic strategies.
In phase-3 clinical trials, the interleukin (IL-1) blocker, rilonacept (IL-1 Trap), demonstrated efficacy for gout flare prevention during initiation of urate-lowering therapy. This trial evaluated ...rilonacept added to a standard-of-care, indomethacin, for treatment of acute gout flares.
Adults, aged 18-70 years, with gout presenting within 48 hours of flare onset and having at least moderate pain as well as swelling and tenderness in the index joint were randomized to subcutaneous (SC) rilonacept 320 mg at baseline plus oral indomethacin 50 mg TID for 3 days followed by 25 mg TID for up to 9 days (n = 74); SC placebo at baseline plus oral indomethacin as above (n=76); or SC rilonacept 320 mg at baseline plus oral placebo (n=75). The primary efficacy endpoint was change in pain in the index joint (patient-reported using a Likert scale (0=none; 4=extreme)) from baseline to the average of values at 24, 48 and 72 hours (composite time point) for rilonacept plus indomethacin versus indomethacin alone. Comparison of rilonacept monotherapy with indomethacin monotherapy was dependent on demonstration of significance for the primary endpoint. Safety evaluation included clinical laboratory and adverse event (AE) assessments.
Patient characteristics were comparable among the groups; the population was predominantly male (94.1%), white (75.7%), with mean±SD age of 50.3±10.6 years. All treatment groups reported within-group pain reductions from baseline (P<0.0001). Although primary endpoint pain reduction was greater with rilonacept plus indomethacin (-1.55±0.92) relative to indomethacin alone (-1.40±0.96), the difference was not statistically significant (P=0.33), so formal comparison between monotherapy groups was not performed. Pain reduction over the 72-hour period with rilonacept alone (-0.69±0.97) was less than that in the other groups, but pain reduction was similar among groups at 72 hours. Treatment with rilonacept was well-tolerated with no reported serious AEs related to rilonacept. Across all groups, the most frequent AEs were headache and dizziness.
Although generally well-tolerated, rilonacept in combination with indomethacin and rilonacept alone did not provide additional pain relief over 72 hours relative to indomethacin alone in patients with acute gout flare.
ClinicalTrials.gov registration number NCT00855920.
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