Software Application Profile: SUMnlmr, an R package that facilitates flexible and reproducible non-linear Mendelian randomisation analyses

Motivation Mendelian randomisation methods that estimate non-linear exposure-outcome relationships typically require individual-level data. This package implements non-linear Mendelian randomisation methods using stratified summarised data, facilitating analyses where individual-level data cannot easily be shared, and additionally increasing reproducibility as summarised data can be reported. Dependence on summarised data means the methods are independent of the form of the individual-level data, increasing flexibility to different outcome types (such as continuous, binary, or time-to-event outcomes). Implementation SUMnlmr is available as an R package (version 3.1.0 or higher). General features The package implements the previously proposed fractional polynomial and piecewise linear methods on stratified summarised data that can either be estimated from individual-level data using the package or supplied by a collaborator. It constructs plots to visualise the estimated exposure-outcome relationship, and provides statistics to assess preference for a non-linear model over a linear model. Availability The package is freely available from GitHub [ https://github.com/amymariemason/SUMnlmr].

New proposed fractional-polynomial functions: new recommendation for overcome the imbalance in three-phase systems

Non-linear loads or load imbalances, etc., are the typical causes of asymmetric operation of three-phase systems. The appearance of inverse (positive) and homopolar (zero) symmetric components cause damage to the systems and electrical equipment and increase the power losses on the transmission lines. Reactive power compensation is one of the solutions that can overcome this asymmetry. The difficulty that exists in many different methods is the optimal calculation of the value of the compensator. In this paper, a new method to overcome these problems is proposed and investigagted. The proposed method is based on the fundamental electrical quantities (voltages and currents) on the controllable values of the static compensation devices and overcoming of the asymmetric operation regime in the three-phase systems.

Blood Pressure, Hypertension and The Risk of Aortic Dissection Incidence and Mortality: results from the Japan-Specific Health Checkups Study, the UK Biobank Study and a Meta-analysis of Cohort Studies

Background: Hypertension or elevated blood pressure (BP) is an important risk factor for aortic dissection (AD); however, few prospective studies concerning this topic have been published. We investigated the association between hypertension/elevated BP and AD in two cohorts and conducted a meta-analysis of published prospective studies, including these two studies. Methods: We analyzed data from the Japan Specific Health Checkups (J-SHC) Study and UK Biobank, which prospectively followed 534,378 and 502,424 participants, respectively. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association of hypertension/elevated BP with AD incidence in the UK Biobank and AD mortality in the J-SHC Study. In the meta-analysis, summary relative risks (RRs) were calculated using random effects models. A potential nonlinear dose-response relationship between BP and AD was tested using fractional polynomial models, and the best-fitting second-order fractional polynomial regression model was determined. Results: In the J-SHC Study and UK Biobank, there were 84 and 182 ADs during 4- and 9-year follow-up, and the adjusted HRs of AD were 3.57 (95% CI, 2.17-6.11) and 2.68 (95% CI: 1.78-4.04) in hypertensive individuals, 1.33 (95% CI: 1.05-1.68) and 1.27 (95% CI: 1.11-1.48) per 20-mmHg increase in systolic BP (SBP), and 1.67 (95% CI: 1.40-2.00) and 1.66 (95% CI: 1.46-1.89) per 10-mmHg increase in diastolic BP (DBP), respectively. In the meta-analysis, the summary RRs were 3.07 (95% CI 2.15-4.38, I2=76.7%, n=7 studies, 2,818 ADs, 4,563,501 participants) for hypertension and 1.39 (95% CI: 1.16-1.66, I2=47.7%, n=3) and 1.79 (95% CI: 1.51-2.12, I2=57.0%, n=3) per 20-mmHg increase in SBP and per 10-mmHg in DBP, respectively. The AD risk showed a strong, positive dose-response relationship with SBP and even more so with DBP. The risk of AD in the nonlinear dose-response analysis was significant at SBP >132 mmHg and DBP >75 mmHg. Conclusions: Hypertension and elevated SBP and DBP are associated with a high risk of AD. The risk of AD was positively dose-dependent, even within the normal BP range. These findings provide further evidence for the optimization of BP to prevent AD.

The Cause and Benefits of GDP

It has recently been shown that world GDP FP-Causes world life expectancy at birth, where FP denotes fractional polynomial (Bechtel, 2021). This article shows that American and Chinese GDPs FP-Cause world life expectancy even more strongly than world GDP does. These striking results beg the question: what FP-Causes American and Chinese GDPs? The answer is globalization, which is also shown here. Furthermore, it is demonstrated that American and Chinese GDPs also FP-Cause world literacy and employment rates. It remains to be seen if the World Bank or International Monetary Fund can show that the GDPs of the other (less affluent) 18 nations in the G20 Fp-cause their country’s life expectancy, as well as their literacy and employment rates. Yearly, pre-pandemic, within-nation increments in these variables can then be compared with subsequent decrements to assess an endogenous viral effect on each country’s well-being. These comparisons will expose inequalities across nations due to the varying wealth of nations. The results in this article are brought by Royston and Altman’s (1994) generalization of polynomial regression, which estimates both coefficients and their powers.

Temporal changes in blood pressure following prehospital rapid sequence intubation

BackgroundRapid Sequence intubation (RSI) is an airway procedure that uses sedative and paralytic drugs to facilitate endotracheal intubation. It is known that RSI could impact blood pressure in the peri-intubation period. However, little is known about blood pressure changes in longer time frames. Therefore, this analysis aims to describe the changes in systolic blood pressure in a large cohort of paramedic-led RSI cases over the whole prehospital timespan.MethodsIntensive Care Paramedics in Victoria, Australia, are authorised to use RSI in medical or trauma patients with a Glasgow Coma Scale <10. This retrospective cohort study analysed data from patientcare records for patients aged 12 years and above that had received RSI, from 1 January 2008 to 31 December 2019. This study quantifies the systolic blood pressure changes using regression with fractional polynomial terms. The analysis is further stratified by high versus Low Shock Index (LSI). The shock index is calculated by dividing pulse rate by systolic blood pressure.ResultsDuring the study period RSI was used in 8613 patients. The median number of blood pressure measurements was 5 (IQR 3–8). Systolic blood pressure rose significantly by 3.4 mm Hg (p<0.001) and then returned to baseline in the first 5 min after intubation for LSI cases. No initial rise in blood pressure is apparent in High Shock Index (HSI) cases. Across the whole cohort, systolic blood pressure decreased by 7.1 mm Hg (95% CI 7.9 to 6.3 mm Hg; p<0.001) from the first to the last blood pressure measured.ConclusionsOur study shows that in RSI patients a small transient elevation in systolic blood pressure in the immediate postintubation period is found in LSI, but this elevation is not apparent in HSI. Blood pressure decreased over the prehospital phase in RSI patients with LSI, but increased for HSI cases.

GDP Almost Perfectly Predicts Survival

This article extends results reported by Bechtel, G. and Bechtel, T. (2021). These previous findings induce the hypothesis confirmed here; namely, that gross domestic product GDP nearly perfectly predicts survival in the world’s entire population. The fractional polynomial regressions here are run over the pre-pandemic period 1991–2016. During the subsequent pandemic, the American Center for Disease Control reported that life expectancy at birth in the USA dropped one year during the first six months of 2020, the largest drop since World War 11. The drops in African and Hispanic life expectancy at birth during this period were 2.7 and 1.9 years (Aljazeera; Democracy Now, February 18, 2021). The USA is the worst covid-19-effected population. It is now imperative to confirm that life expectancy at birth is well predicted from GDP in all nations over 1991–2018. This pre-pandemic control for each nation will accurately calibrate it’s subsequent yearly survival drops due to Covid-19. This is especially important in light of the trade war between the United States and China, which has increased the need for accurate measurement of the human effects of this war.

The Association between Serum Concentration of Irisin, Glucose-dependent Insulinotropic Polypeptide and Body Mass Index among Women with and without Polycystic Ovary Syndrome

Background: The actions of adipocytokines may be a connective factor between obesity and polycystic ovary syndrome (PCOS). It is suggested that irisin, as recently described cytokine secreted by skeletal muscles and glucose-dependent insulinotropic polypeptide (GIP) as an incretin hormone that induces cytokine expression, may play key roles in favoring obesity in these women. Objectives: We aimed to evaluate the association between body mass index (BMI) and serum concentration of irisin/GIP in women with and without PCOS in the linear and non-linear model. Methods: This cross-sectional study was conducted among 159 PCOS and 82 healthy eumenorrheic non-hirsute women aged 20 - 50 years. The fractional-polynomial model was used to develop a model of continuous risk factors, which evaluates non-linear associations between irisin/GIP and BMI among women with and without PCOS. Results: Women with PCOS were significantly younger (28.2 ± 5.8 vs. 33.0 ± 7.8 years, P < 0.001) and had a greater BMI (26.6 ± 5.2 vs. 25.2 ± 4.8 kg/m2, P = 0.04) than the healthy counterparts. There were no significant linear and non-linear associations between serum concentration of irisin/GIP and BMI in both groups. The analysis of pair-wise age and BMI matching of women with PCOS and controls confirmed these findings. Conclusions: This study showed that irisin and GIP have no association with BMI in women with or without PCOS. This finding could help to better understand the underlying pathophysiological status of PCOS, insulin resistance, and obesity-related disorders. Further large cohort studies are needed to confirm these findings.

The Impact of Time Interval between Hepatic Resection and Liver Transplantation on Clinical Outcome in Patients with Hepatocellular Carcinoma

Hepatic resection (HR) for hepatocellular carcinoma (HCC) may require secondary liver transplantation (SLT). However, a previous HR is supposed to worsen post-SLT outcomes. Data of patients treated by SLT between 2000 and 2018 at two tertiary referral centers were analyzed. The primary outcome of the study was to analyze the impact of HR on post-LT complications. A Comprehensive Complication Index ≥ 29.6 was chosen as cutoff. The secondary outcome was HCC-related death by means of competing-risk regression analysis. In the study period, 140 patients were included. Patients were transplanted in a median of 23 months after HR (IQR 14–41). Among all the features analyzed regarding the prior HR, only time interval between HR and SLT (time HR-SLT) was an independent predictor of severe complications after LT (OR = 0.98, p < 0.001). According to fractional polynomial regression, the probability of severe complications increased up to 15 months after HR (43%), then slowly decreased over time (OR = 0.88, p < 0.001). There was no significant association between HCC-related death and time HR-SLT at the multivariable competing risks regression model (SHR, 1.06; 95% CI: 0.69–1.62, p = 0.796). This study showed that time HR-SLT was key in predicting complications after LT, without affecting HCC-related death.

Chinese Fetal Biometry: Establishment of a Formula for Calculating Gestational Age based on Crown–Rump Length Measurements

Background: To develop an ultrasonographic dating formula for predicting gestational age (GA) based on fetal crown–rump length (CRL) in a Chinese population, evaluate its systematic prediction error and compare it with existing formulae.Methods: This was a prospective cross-sectional study of spontaneously conceived singleton pregnancies among women with a regular menstrual cycle in the preceding year. Ultrasound examinations were performed at 11–14 weeks according to the date of the last menstrual cycle. The CRL was measured three times for each fetus, and the mean was used to derive the best-fit fractional polynomial regression model for estimation of GA in relation to CRL. For each fetus, the GA was compared with the GA calculated using six established dating formulae based on CRL measurements. The means of the differences between estimated and menstrual age were calculated for each formula. All the women were followed up routinely until the birth of the fetus. Results: Of the 4710 subjects recruited, the mean and standard deviation values of CRL changed linearly with GA. The corresponding regression equation and its correlation coefficient (R2) was GA = 59.361513 + 0.461425 ´ CRL (R2 = 0.8028). The mean difference between estimated and menstrual age was 0.22 days (95% confidence interval 0.05–0.21), lower than that of the six existing CRL dating formulae.Conclusions: We have derived a CRL-based dating formula suitable for naturally conceived pregnancies for GA between 11+0 and 13+6 weeks. The formula has no systematic prediction error, comparing favorably with the existing published dating formulae.