A randomized clinical trial to stimulate the cholinergic anti-inflammatory pathway in patients with moderate COVID-19-pneumonia using a slow-paced breathing technique

ImportanceVagus nerve stimulation via slow-paced breathing could serve as adjuvant therapeutic approach to reduce excessive inflammation in coronavirus disease 2019 (COVID-19) pneumonia.ObjectiveDoes a slow-paced breathing technique increasing vagal activity reduce Interleukin-6 (IL-6) in patients hospitalized with moderate COVID-19 pneumonia compared to standard care?DesignSingle-center randomized controlled clinical trial with enrolment from February 23rd 2021 through June 17th 2021 and follow-up until July 22nd 2021.SettingWard for infectious diseases and temporary COVID-19 ward, Ulm University Hospital, GermanyParticipantsConsecutive sample of patients hospitalized with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (primary diagnosis). Of 131 patients screened, 48 patients were randomized and 46 patients analyzed (N=23 per group).InterventionsSlow-paced 20-minute breathing exercise three times a day with six breaths per minute (inhale-to-exhale ratio 4:6).Main outcomes and measuresDifferences between intervention and control group in IL-6 calculated using multilevel mixed-effect linear regression models with random slope including the covariates relevant comorbidities, COVID-19 medication, and age.ResultsMean age 57 years±13 years, N= 28 (60%) male, N=30 (65%) with relevant comorbidities. The model including group by time interaction revealed a significantly lower trajectory of IL-6 in the intervention group compared to the control group (effect size Cohens f2=0.11, LR-test p=.040) in the intention-to-treat sample, confirmed by treatment-per-protocol analysis (f2=0.15, LR-test p=.022).Exploratory analysis using the median split of practice time to predict IL-6 of the next morning indicated a dose-response relationship with beneficial effects of practice time above 45 minutes a day.Three patients in each group were admitted at ICU, one died. Oxygen saturation increased during slow-paced breathing (from 95.1%±2.1% to 95.4%±1.6%, p=0.006).Conclusion and relevancePatients practicing slow-paced breathing had significantly lower IL-6 values than controls without relevant side effects. Further trials should evaluate clinical outcomes as well as an earlier start of the intervention, i.e., at symptom onset. This would offer an access to a therapy option not only for high-income, but also for low- and middle-income countries.Trial registrationGerman register of clinical trials (ID: DRKS00023971) https://www.drks.de, Universal Trial Number (UTN) U1111-1263-8658;Key pointsQuestionCan slow-paced breathing reduce Interleukin-6 (IL-6) in hospitalized patients with moderate coronavirus disease 2019 (COVID-19) pneumonia?FindingsSingle-center randomized controlled clinical trial including 46 patients hospitalized with moderate COVID-19 pneumonia. Compared to controls, IL-6 values were significantly lower (small-to-medium effect sizes) in patients who were instructed to practice six breaths per minute for 20 minutes three times a day. More minutes of slow-paced breathing were significantly correlated with lower IL-6 values the next morning.MeaningSlow-paced breathing could be a safe and feasible adjuvant therapeutic approach in moderate COVID-19 pneumonia.

Pyrethroid Resistance in Anopheles gambiae Not Associated with Insecticide-Treated Mosquito Net Effectiveness Across Sub-Saharan Africa

Pyrethroid resistance is a major concern for malaria vector control programs that predominantly rely on insecticide-treated mosquito nets (ITNs). Contradictory results of the impact of resistance have been observed during field studies. We combined continent-wide estimates of pyrethroid resistance in Anopheles gambiae from 2006 to 2017, with continent-wide survey data to assess the effect of increasing pyrethroid resistance on the effectiveness of ITNs to prevent malaria infections in sub-Saharan Africa. We used a pooled-data approach and a meta-regression of survey regions to assess how pyrethroid resistance affects the association between ITN ownership and malaria outcomes for children 6 to 59 months of age. ITN ownership reduced the risk of malaria outcomes according to both the pooled and meta-regression approaches. According to the pooled analysis, there was no observed interaction between ITN ownership and estimated level of pyrethroid resistance (likelihood ratio [LR] test, 1.127 for malaria infection confirmed by the rapid diagnostic test, P = 0.2885; LR test = 0.161 for microscopy-confirmed malaria infection, P = 0.161; LR test = 0.646 for moderate or severe anemia, P = 0.4215). Using the meta-regression approach to determine the level of pyrethroid resistance did not explain any of the variance in subnational estimates of ITN effectiveness for any of the outcomes. ITNs decreased the risk of malaria independent of the levels of pyrethroid resistance in malaria vector populations.

Neutrophil-Related Ratios Predict the 90-Day Outcome in Acute Ischemic Stroke Patients After Intravenous Thrombolysis

Background and PurposeMounting researches have illuminated that the neutrophil-related ratios were related to the prognosis of acute ischemic stroke (AIS). However, few have compared their predictive value and accuracy. To make such comparison and identify the best indicator on the 90-day outcome, we investigated biomarkers including neutrophil ratio (Nr), neutrophil count (Nc), lymphocyte (L), neutrophil-to-lymphocyte ratio (NLR), platelet (P or PLT), platelet-to-neutrophil ratio (PNR), NLR-to-platelet ratio (NLR/PLT), eosinophil (E), neutrophil-to-eosinophil ratio (NER), monocyte (M), and monocyte-to-neutrophil ratio (MNR).MethodsThis retrospective study recruited 283 AIS and 872 healthy controls (HCs) receiving intravenous thrombolysis (IVT). Blood samples were collected after 24 h of admission before IVT. Propensity Score Matching (PSM) was used to explore whether these ratios differentiated AIS and HCs. We applied univariate and multivariate analyses to evaluate the prediction effect of these ratios separately or added in the model and figured out a clinical prediction model. To estimate the discrimination and calibration of the new models, the receiver operating characteristics (ROC) curve analysis, DeLong method, and likelihood ratio test (LR test) were utilized.ResultsPSM showed that Nr, Nc, NLR, P, PNR, NLR/PLT, NER, and MNR facilitates the differentiation of the HCs and AIS. Among the eight biomarkers, PNR and MNR could differentiate the 90-day outcome, and it was found out that PNR performed better. Univariate regression analysis demonstrated that PNR was the only independent predictor which needs no adjustment. Besides, the multivariate regression analysis, Delong method, and LR test indicated that among the neutrophil-related ratios, NLR, PNR, NLR/PLT, NER, and MNR exerted little influence on the discrimination but could enhance the calibration of the base model, and NER proved to work best.ConclusionLow PNR was the best indicator among the neutrophil-related ratios tin predicting a poor 90-day outcome of AIS patients. Moreover, high NER performed best when predicting the 90-day outcome to improve the calibration of the base model.

The Role of Organizational Development in Achieving the Competitive Advantage of University of Hail as one of the requirements of The vision of the Kingdom of Saudi Arabia 2030

This study explores interactive e-book cues and Information Processing Levels (IPL)’s effectiveness on Learning Retention (LR) and External Cognitive Load (ECL). 117 middle school pupils (MSP) were divided into six experimental groups based on their IPL and cues during the second term of the academic year 2019–2020. Visual Cues (VC)/Audiovisual Cues (VAC) and Auditory Cues (AC)/Audiovisual Cues (VAC) statistically varied in the Ie-book in LR test and ECL scale, same for the average scores when testing the LR in Science for MSP due to the difference between IPL for the DL. There is a statistically significant effect of cue types' interaction in Ie-book with IPL in ECL scale for MSP, at its highest peak in the case of the AVC with DL, followed by the interaction resulting from the VC with DL then AC with SL. Also, cues interaction in Ie-book with IPL immensely affect the LR test for MEP, which is at its highest peak in the case of the AVC with DL. The interactions between (DL–SL) and (AC–VC) seem to equally influence the ELC.

The Effectiveness of the Interaction of Interactive Book Cues and Levels of Information Processing on Learning Retention and External Cognitive Load

This study explores interactive e-book cues and Information Processing Levels (IPL)’s effectiveness on Learning Retention (LR) and External Cognitive Load (ECL). 117 middle school pupils (MSP) were divided into six experimental groups based on their IPL and cues during the second term of the academic year 2019–2020. Visual Cues (VC)/Audiovisual Cues (VAC) and Auditory Cues (AC)/Audiovisual Cues (VAC) statistically varied in the Ie-book in LR test and ECL scale, same for the average scores when testing the LR in Science for MSP due to the difference between IPL for the DL. There is a statistically significant effect of cue types' interaction in Ie-book with IPL in ECL scale for MSP, at its highest peak in the case of the AVC with DL, followed by the interaction resulting from the VC with DL then AC with SL. Also, cues interaction in Ie-book with IPL immensely affect the LR test for MEP, which is at its highest peak in the case of the AVC with DL. The interactions between (DL–SL) and (AC–VC) seem to equally influence the ELC

The Periodic Restricted EXPAR(1) Model

In this chapter, we discuss the nonlinear periodic restricted EXPAR(1) model. The parameters are estimated by the quasi maximum likelihood (QML) method and we give their asymptotic properties which lead to the construction of confidence intervals of the parameters. Then we consider the problem of testing the nullity of coefficients by using the standard Likelihood Ratio (LR) test, simulation studies are given to assess the performance of this QML and LR test.

Using the Standardized Root Mean Squared Residual (SRMR) to Assess Exact Fit in Structural Equation Models

We examine the accuracy of p values obtained using the asymptotic mean and variance (MV) correction to the distribution of the sample standardized root mean squared residual (SRMR) proposed by Maydeu-Olivares to assess the exact fit of SEM models. In a simulation study, we found that under normality, the MV-corrected SRMR statistic provides reasonably accurate Type I errors even in small samples and for large models, clearly outperforming the current standard, that is, the likelihood ratio (LR) test. When data shows excess kurtosis, MV-corrected SRMR p values are only accurate in small models ( p = 10), or in medium-sized models ( p = 30) if no skewness is present and sample sizes are at least 500. Overall, when data are not normal, the MV-corrected LR test seems to outperform the MV-corrected SRMR. We elaborate on these findings by showing that the asymptotic approximation to the mean of the SRMR sampling distribution is quite accurate, while the asymptotic approximation to the standard deviation is not.

Pyrethroid resistance in Anopheles gambiae not associated with insecticide-treated mosquito net effectiveness across sub-Saharan Africa

BackgroundPyrethroid resistance is a major concern for malaria vector control programs that predominantly rely on insecticide-treated mosquito nets (ITN). Contradictory results of the impact of resistance have been observed in field studies.MethodsWe combined continent-wide estimates of pyrethroid resistance in Anopheles gambiae from 2006-2017 with continent-wide survey data to assess the effect of increasing pyrethroid resistance on the effectiveness of ITNs to prevent malaria infections in sub-Saharan Africa. We utilized both a pooled-data approach and meta-regression of survey regions to assess how pyrethroid resistance affects the association between ITN ownership and malaria outcomes in children aged 6-59 months.FindingsITN ownership reduced the risk of malaria outcomes in both pooled and meta-regression approaches. In the pooled analysis, there was no observed interaction between ITN ownership and estimated level of pyrethroid resistance (Likelihood ratio [LR] test = 1.127 for the outcome of rapid diagnostic test confirmed malaria infection, p = 0.2885; LR test = 0.161 for the outcome of microscopy confirmed malaria infection, p = 0.161; LR test = 0.646 for the outcome of moderate or severe anemia, p = 0.4215). In the meta-regression approach the level of pyrethroid resistance did not explain any of the variance in subnational estimates of ITN effectiveness for any of the outcomes.InterpretationITNs decreased risk of malaria outcomes independent of the levels of pyrethroid resistance in the malaria vector populations.FundingDAL did not receive funding and RC received a SOURCE grant from Syracuse University for this project.

Managerial overconfidence, debt capacity and merger & acquisition premium

Purpose Based on the perspective of cognitive psychology, this paper takes the M&A events of Chinese A-share listed enterprises from 2008 to 2015 as the research samples, and then empirically analyzes the influence of managerial overconfidence on M&A premium under the special circumstances in China and tests the moderating effect of debt capacity between managerial overconfidence and M&A premium. Design/methodology/approach This paper selects the M&A events of all A-share listed enterprises from 2008 to 2015 as the total samples. In view of the fact that the data in this paper are unbalanced panel data, so this paper uses the LR test, LR test and Hausman test to filter the mixed OLS model, fixed effect model and random effect model. Finally, using the random effect model for empirical testing reduces the endogeneity of the model. Findings The study shows that managerial overconfidence is positively correlated with M&A premium; at the same time, compared with the state-owned enterprises, the relationship between managerial overconfidence and M&A premium is more significant in private enterprises. Further study shows that debt capacity can strengthen the relationship between managerial overconfidence and M&A premium, to be specific, the larger the debt capacity is, the stronger the positive relationship between managerial overconfidence and M&A premium will be. Moreover, after considering the influence of agency cost and financing expense, and conducting endogenous test and robust test, this research’s conclusions remain the same. Research limitations/implications This research also has some limitations. Some M&A announcements are incomplete, and the target has more information missing, resulting in a decrease in the number of samples, which may affect the accuracy of the conclusions. This paper does not address the research of the economic consequences of M&A, namely, the impact of managerial overconfidence and debt capacity on M&A performance. This is one of the future research directions for this paper. Practical implications The conclusions of this paper provide new theory evidence for Chinese enterprises' M&A decision-making. Social implications First, enterprises should gradually improve corporate governance structure and governance mechanisms to guide more stakeholders to participate in corporate governance, and also they should strengthen the pre-evaluation, in-process control and post-supervision of managers' behavioral decisions to prevent irrational M&A caused by managerial overconfidence. Especially in private enterprises, this issue should be paid more attention. Second, enterprises should make full use of the debt governance function of creditors and improve the creditors' supervision mechanism for managers' decision-making behavior. Originality/value The innovation value and increment contribution of this paper may include the following aspects: the conclusions of this paper expand the research boundary of the relationship between managerial overconfidence and M&A premium, and enrich related literature about debt capacity and the influence of debt capacity on M&A decision-making, and also provide new theory evidence for Chinese enterprises' M&A decision-making. In a word, this research is a beneficial supplement and extension for existing research.

Inequality Indices as Tests of Fairness

Inequality indices are traditionally interpreted as measures of deviations from equality. This article interprets them instead as statistical tests for a null of fairness within well-defined income generating processes. We find that the likelihood ratio (LR) test for fairness versus unfairness within two such processes are proportional to Theil’s first and second inequality indices respectively. The LR values may be used either as a test statistic or to approximate a Bayes factor that measures the posterior probabilities of the fair version of the processes over that of the unfair. We also apply this perspective to measurement of inequality of opportunity.