Experience of management of pediatric upper gastrointestinal perforations: a series of 30 cases

BackgroundThis study aimed to explore the characteristics of pediatric upper gastrointestinal (UGI) perforations, focusing on their diagnosis and management.MethodsBetween January 2013 and December 2021, 30 children with confirmed UGI perforations were enrolled, and their clinical data were analyzed. Two groups were compared according to management options, including open surgical repair (OSR) and laparoscopic/gastroscopic repair (LR).ResultsA total of 30 patients with a median age of 36.0 months (1 day–17 years) were included in the study. There were 19 and 11 patients in the LR and OSR groups, respectively. In the LR group, two patients were treated via exploratory laparoscopy and OSR, and the other patients were managed via gastroscopic repair. Ten and three patients presented the duration from symptom onset to diagnosis within 24 h (p = 0.177) and the number of patients with hemodynamically unstable perforations was 4 and 3 in the LR and OSR groups, respectively. Simple suture or clip closure was performed in 27 patients, and laparoscopically pedicled omental patch repair was performed in two patients. There was no significant difference in operative time and length of hospital stay between the LR and OSR groups. Treatment failed in two patients because of severe sepsis and multiple organ dysfunction syndrome, including one with fungal peritonitis.ConclusionSurgery for pediatric UGI perforations should be selected according to the general status of the patient, age of the patient, duration from symptom onset, inflammation, and perforation site and size. Antibiotic administration and surgical closure remain the main strategies for pediatric UGI perforations

Research on the mechanism of the role of national science and technology awards on science and technology innovation: Based on the case of award-winning projects in the power company

The National Science and Technology Award is a recognition of the highest level of science and technology projects in China, which has an extraordinary incentive effect on science and technology innovation. By referring to Michael Porter diamond model, the incentive diamond model of science and technology awards is constructed. It is considered that the incentive effect of science and technology awards on enterprise science and technology innovation is mainly through influencing the foundation and motivation of science and technology innovation, which is thus implemented in four aspects: leading the advancement of technology, promoting economic development, supporting policy implementation, and cultivating research teams. Based on the case of “Qinshan 600 MW Nuclear Power Plant Design and Construction” project in the power industry, the model is confirmed. It is argued that the superiority and inferiority effect brought by national science and technology rewards can help China build a leading science and technology enterprise and build a world science and technology power

A Comparison of Frequentist and Bayesian Model Based Approaches for Missing Data Analysis: Case Study with a Schizophrenia Clinical Trial

<p>Missing data are common in clinical trials and could lead to biased estimation of treatment effects. The National Research Council (NRC) report suggests that sensitivity analysis on missing data mechanism should be a mandatory component of the primary reporting of findings from clinical trials, and regulatory agencies are requesting more thorough sensitivity analyses from sponsors. However, recent literature research showed that missing data were almost always inadequately handled. This is partially due to the lack of standard software packages and straightforward implementation platform. With recent availability of flexible Bayesian software packages such as WinBUGS, SAS Proc MCMC, and Stan, it is relatively simple to develop Bayesian methods to address complex missing data problems while incorporating the uncertainty. In this article, we present a case study from the DIA Bayesian Scientific Working Group (BSWG) on Bayesian approaches for missing data analysis. We illustrate how to use Bayesian approaches to fit a few commonly used frequentist missing data models. The properties, advantage, and flexibility of the Bayesian analysis methods will be discussed using a case study based on a schizophrenia clinical trial. Supplementary materials for this article are available online.</p

Tailoring the Atomic-Local Environment of Carbon Nanotube Tips for Selective H₂O₂ Electrosynthesis at High Current Densities

The atomic-local environment of catalytically active sites plays an important role in tuning the activity of carbon-based metal-free electrocatalysts (C-MFECs). However, the rational regulation of the environment is always impeded by synthetic limitations and insufficient understanding of the formation mechanism of the catalytic sites. Herein, the possible cleavage mechanism of carbon nanotubes (CNTs) through the crossing points during ball-milling is proposed, resulting in abundant CNT tips that are more susceptible to be modified by heteroatoms, achieving precise modulation of the atomic environment at the tips. The obtained CNTs with N,S-rich tips (N,S-TCNTs) exhibit a wide potential window of 0.59 V along with H2O2 selectivity for over 90.0%. Even using air as the O-2 source, the flow cell system with N,S-TCNTs catalyst attains high H2O2 productivity up to 30.37 mol g(cat.)(-1) h(-1)@350 mA cm(-2), superior to most reported C-MFECs. From a practical point of view, a solid electrolyzer based on N,S-TCNTs is further employed to realize the in-situ continuous generation of pure H2O2 solution with high productivity (up to 4.35 mmol cm(-2) h(-1)@300 mA cm(-2); over 300 h). The CNTs with functionalized tips hold great promise for practical applications, even beyond H2O2 generation

The Amino-Acid Substituents of Dipeptide Substrates of Cathepsin C Can Determine the Rate-Limiting Steps of Catalysis

We examined the cathepsin C-catalyzed hydrolysis of dipeptide substrates of the form Yaa-Xaa-AMC, using steady-state and pre-steady-state kinetic methods. The substrates group into three kinetic profiles based upon the broad range observed for <i>k</i>_cat/<i>K</i>_a and <i>k</i>_cat values, pre-steady-state time courses, and solvent kinetic isotope effects (sKIEs). The dipeptide substrate Gly-Arg-AMC displayed large values for <i>k</i>_cat/<i>K</i>_a (1.6 ± 0.09 μM^–1 s^–1) and <i>k</i>_cat (255 ± 6 s^–1), an inverse sKIE on <i>k</i>_cat/<i>K</i>_a (^D(<i>k</i>_cat/<i>K</i>_a) = 0.6 ± 0.15), a modest, normal sKIE on <i>k</i>_cat (^D<i>k</i>_cat = 1.6 ± 0.2), and immeasurable pre-steady-state kinetics, indicating an extremely fast pre-steady-state rate (>400 s^–1). (Errors on fitted values are omitted in the text for clarity but may be found in Table 2.) These results conformed to a kinetic model where the acylation (<i>k</i>_ac) and deacylation (<i>k</i>_dac) half-reactions are very fast and similar in value. The second substrate type, Gly-Tyr-AMC and Ser-Tyr-AMC, the latter the subject of a comprehensive kinetic study (Schneck et al. (2008) <i>Biochemistry 47</i>, 8697–8710), were found to be less active substrates compared to Gly-Arg-AMC, with respective <i>k</i>_cat/<i>K</i>_a values of 0.49 ± 0.07 μM^–1s^–1 and 5.3 ± 0.5 μM^–1s^–1, and <i>k</i>_cat values of 28 ± 1 s^–1 and 25 ± 0.5 s^–1. Solvent kinetic isotope effects for Ser-Tyr-AMC were found to be inverse for <i>k</i>_cat/<i>K</i>_a (^D(<i>k</i>_cat/<i>K</i>_a) = 0.74 ± 0.05) and normal for <i>k</i>_cat (^D<i>k</i>_cat = 2.3 ± 0.1) but unlike Gly-Arg-AMC, pre-steady-state kinetics of Gly-Tyr-AMC and Ser-Tyr-AMC were measurable and characterized by a single-exponential burst, with fast transient rates (490 s^–1 and 390 s^–1, respectively), from which it was determined that <i>k</i>_ac ≫ <i>k</i>_dac ∼ <i>k</i>_cat. The third substrate type, Gly-Ile-AMC, gave very low values of <i>k</i>_cat/<i>K</i>_a (0.0015 ± 0.0001 μM^–1 s^–1) and <i>k</i>_cat (0.33 ± 0.02 s^–1), no sKIEs, (^D(<i>k</i>_cat/<i>K</i>_a) = 1.05 ± 0.5 and ^D<i>k</i>_cat = 1.06 ± 0.4), and pre-steady-state kinetics exhibited a discernible, but negligible, transient phase. For this third class of substrate, kinetic modeling was consistent with a mechanism in which <i>k</i>_dac > <i>k</i>_ac ∼ <i>k</i>_cat, and for which an isotope-insensitive step in the acylation half-reaction is the slowest. The combined results of these studies suggested that the identity of the amino acid at the P₁ position of the substrate is the main determinant of catalysis. On the basis of these kinetic data, together with crystallographic studies of substrate analogues and molecular dynamics analysis with models of acyl-enzyme intermediates, we present a catalytic model derived from the relative rates of the acylation vs deacylation half-reactions of cathepsin C. The chemical steps of catalysis are proposed to be dependent upon the conformational freedom of the amino acid substituents for optimal alignment for thiolation (acylation) or hydrolysis (deacylation). These studies suggest ideas for inhibitor design for papain-family cysteine proteases and strategies to progress drug discovery for other classes of disease-relevant cysteine proteases