Confidence interval estimation for vaccine efficacy against COVID-19.

This article focuses on the construction of a confidence interval for vaccine efficacy against contagious coronavirus disease-2019 (COVID-19) in a fixed number of events design. Five different approaches are presented, and their performance is investigated in terms of the two-sided coverage probability, non-coverage probability at the lower tail, and expected confidence interval width. Furthermore, the effect of under-sensitivity of diagnosis tests on vaccine efficacy estimation was evaluated. Except for the exact conditional method, the non-coverage probability of the remaining methods may exceed the nominal significance level, e.g., 5%, even for a large number of total confirmed COVID-19 cases. The narrower confidence interval width from the Bayesian, approximate Poisson, and mid-P methods are on the cost of increased instability of coverage probability. When the sensitivity of diagnosis test in the vaccine group is lower than that in the placebo group, the reported vaccine efficacy tends to be overly optimistic. The exact conditional method is preferable to other methods in COVID-19 vaccine efficacy trials when the total number of cases reaches 60; otherwise, mid-p method can be used to obtain a narrower interval width.

Metformin ameliorates TGF-ß1-induced osteoblastic differentiation of human aortic valve interstitial cells by inhibiting ß-catenin signaling.

Osteoblastic differentiation of aortic valve interstitial cells (AVICs) is the central process in the development of calcific aortic valve disease (CAVD). Metformin is a widely used first-line antidiabetic drug, and recently, pleiotropic benefits of metformin beyond hypoglycemia have been reported in the cardiovascular system. Here, we examined the effect of metformin on the osteoblastic differentiation of human AVICs. Our results showed that metformin ameliorated TGF-ß1-induced production of osteogenic proteins Runx2 and osteopontin as well as calcium deposition in the cultured human AVICs. Experiments using AICAR, Compound C and AMPKα siRNA showed that the beneficial effect of metformin on TGF-ß1-induced osteoblastic differentiation of human AVICs was mediated by AMPKα. Moreover, metformin inhibited the TGF-ß1-induced activation of ß-catenin, and ß-catenin siRNA blocked TGF-ß1-induced osteoblastic differentiation of AVICs. Smad2/3 and JNK were phosphorylated to promote the TGF-ß1-induced activation of ß-catenin and osteoblastic differentiation of AVICs, and metformin also alleviated TGF-ß1-induced activation of Smad2/3 and JNK. In conclusion, our results suggest a beneficial effect of metformin based on the prevention of osteoblastic differentiation of human AVICs via inhibition of ß-catenin, which indicates the therapeutic potential of metformin for CAVD.

Contraception and Unintended Pregnancy among Unmarried Female University Students: A Cross-sectional Study from China.

This study aims to understand the level of contraceptive knowledge and attitudes towards contraception, and then to explore the association between the contraceptive behavior and unintended pregnancy in unmarried female university students in China. A cross-sectional study was conducted of university students in 49 universities across 7 cities in China from September 2007 to January 2008. We distributed 74,800 questionnaires, of which 69,842 were returned. In this paper, the data from 35,383 unmarried female university students were analyzed. The prevalence of sexual intercourse in unmarried female university students was 10.2%. The prevalence of unintended pregnancy in those sexually active female university students, was 31.8%. Among students with pregnancy, 53.5% experienced two or more pregnancies. 28.3% of the students with sexual intercourse reported that they always adopted contraceptive methods, and of those 82.9% chose to use male condoms. The majority (83.9%) of students with unintended pregnancy chose to terminate the latest pregnancy by surgical abortion or medical abortion. The contraceptive knowledge level of students who experienced unintended pregnancy was lower than those who did not. In China, about one third of unmarried female students with sexual intercourse experience unintended pregnancy. A variety of contraceptive methods are adopted, but the frequency of contraceptive use is low. Most of unmarried female students who experienced unintended pregnancy would choose to terminate the pregnancy with surgical or medical abortion. University students, especially the ones who have experienced unintended pregnancy, lack contraceptive and reproductive health knowledge.

Evaluation of semen quality in 1808 university students, from Wuhan, Central China.

The aim of this study was to evaluate the semen quality of university students in Wuhan, the largest city in the world in terms of the number of university students. All student sperm donors recorded in the Hubei Province Human Sperm Bank from 1 March 2010 to 31 December 2013 were screened. At last, a total of 3616 semen samples from 1808 university student sperm donors were eligible and retrospectively analyzed. Each donor's semen parameters were averaged over two samples and compared with the World Health Organization criteria, and a generalized linear regression model was used to examine several determinants of semen quality. We found that the mean and median values were 3.0 ml and 2.8 ml for semen volume, 50.2 × 10 6 ml-1 and 50.0 × 10 6 ml-1 for sperm concentration, 148.1 × 10 6 and 142.1 × 10 6 for total sperm count, and 58.6% and 60.0% for total sperm motility. About 85.0% of donors had parameters that were all normal. Season and duration of abstinence were critical factors affecting semen quality. We also found a decrease in sperm concentration during the 4 years observation; however, this may not be a strong evidence to confirm the declining trend of semen quality. In conclusion, semen quality of university students in Wuhan was not optimal and should be paid high attention, long-term observation and further study should be carried out to confirm the present situation.

Transmission/disequilibrium tests incorporating unaffected offspring.

We propose a new method for family-based tests of association and linkage called transmission/disequilibrium tests incorporating unaffected offspring (TDTU). This new approach, constructed based on transmission/disequilibrium tests for quantitative traits (QTDT), provides a natural extension of the transmission/disequilibrium test (TDT) to utilize transmission information from heterozygous parents to their unaffected offspring as well as the affected offspring from ascertained nuclear families. TDTU can be used in various study designs and can accommodate all types of independent nuclear families with at least one affected offspring. When the study sample contains only case-parent trios, the TDTU is equivalent to TDT. Informative-transmission disequilibrium test (i-TDT) and generalized disequilibrium test(GDT) are another two methods that can use information of both unaffected offspring and affected offspring. In contract to i-TDT and GDT, the test statistic of TDTU is simpler and more explicit, and can be implemented more easily. Through computer simulations, we demonstrate that power of the TDTU is slightly higher compared to i-TDT and GDT. All the three methods are more powerful than method that uses affected offspring only, suggesting that unaffected siblings also provide information about linkage and association.