Importance Despite lack of evidence of their utility, biomarkers of ovarian reserve are being promoted as potential markers of reproductive potential or “fertility tests.” Objective To determine the extent to which biomarkers of ovarian reserve are associated with reproductive potential among late-reproductive age women. Design, Setting, and Participants Prospective, time-to-pregnancy cohort study (2008-March 2016) of women (N=981) 30–44 years of age without a history of infertility who had been trying to conceive for 3 months or less were recruited from the community in the Raleigh-Durham area. Exposures Early follicular phase serum level of antimüllerian hormone (AMH), follicle stimulating hormone (FSH), and inhibin B, and urinary level of FSH. Main Outcomes and Measures The primary outcomes were the cumulative probability of conception by 6 and 12 cycles of attempt and relative fecundability, the probability of conception in a given menstrual cycle. Conception was defined as a positive pregnancy test. Results 750 women (33.3[3.2] years of age; 77% white; 36% overweight or obese), provided a blood and urine sample and were included in the analysis. After adjusting for age, body mass index, race, current smoking status and recent hormonal contraceptive use, women with low AMH values (<0.7ng/ml, N=84) did not have a significantly different predicted probability of conceiving by 6 cycles of attempt (65%; 95% Confidence Interval (CI): 50–75%) compared to women (N=579) with normal values (62%; 95% CI: 57–66%) nor by 12 cycles of attempt (84%; 95% CI: 70–91% versus 75%; 95% CI: 70–79%, respectively). Women with high serum FSH values (>10mIU/ml, N=83) did not have a significantly different predicted probability of conceiving after 6 cycles of attempt (63%; 95% CI: 50–73%) compared to women (N=654) with normal values (62%; 95% CI: 57–66%) nor after 12 cycles of attempt (82%; 95% CI: 70–89 versus 75%; 95% CI: 70–78%). Women with high urinary FSH values (>11.5mIU/mgcr, N=69) did not have a significantly different predicted probability of conceiving after 6 cycles of attempt (61%; 95% CI: 46–74%) compared to women (N=660) with normal values (62%; 95% CI: 58–66%) nor after 12 cycles of attempt (70%; 95% CI: 54–80% versus 76%; 95% CI: 72–80%). Inhibin b levels (N=737) were not associated with the probability of conceiving in a given cycle (Hazard Ratio [per 1pg/ml increase] = 0.999; 95% CI: 0.997–1.001). Conclusions Among women age 30–44 years of age without a history of infertility, who had been trying to conceive for 3 months or less, biomarkers indicating diminished ovarian reserve, compared to normal ovarian reserve, were not associated with reduced fertility. These findings do not support the use of urinary or blood FSH tests or AMH levels to assess natural fertility for women with these characteristics.
A cohort of 1,804 residents of Rochester, Minnesota, who were at least 50 years old, free of stroke, and who underwent examination at the Mayo Clinic in 1960, was followed for 13 years. During this period, there were 110 first ischemic strokes and 616 deaths without stroke. The time of onset, if available, or the time of diagnosis of potential risk factors was determined for all patients during the study and was used to construct a proportional hazards model of time to occurrence of stroke with time-dependent risk factors. The model included 8 risk factors (2 fixed and 6 time-dependent). For these, the individual relative risks are: 1.6 for age (per 10 years), 2.0 for males, 4.0 for definite hypertension, 3.9 for transient ischemic attacks, 2.2 for hypertensive heart disease, 2.2 for coronary heart disease, 1.7 for congestive heart failure, and 1.7 for diabetes mellitus. Atrial fibrillation was not a significant risk factor using time-dependent multivariate analysis.
The recent increase in extensively drug-resistant bacterial pathogens and the associated increase of morbidity and mortality demonstrate the immediate need for new antibiotic backbones with novel mechanisms of action. Here, we report the development of the PepSAVI-MS pipeline for bioactive peptide discovery. This highly versatile platform employs mass spectrometry and statistics to identify bioactive peptide targets from complex biological samples. We validate the use of this platform through the successful identification of known bioactive peptides from a botanical species, Viola odorata. Using this pipeline, we have widened the known antimicrobial spectrum for V. odorata cyclotides, including antibacterial activity of cycloviolacin O2 against A. baumannii. We further demonstrate the broad applicability of the platform through the identification of novel anticancer activities for cycloviolacins by their cytotoxicity against ovarian, breast, and prostate cancer cell lines.
Results suggest that integrated youth in the U.S. may engage in healthier eating behaviors than those who are assimilated. Additional research on Hispanic/Latino youths' acculturation and diet can inform health promotion efforts to improve eating habits and health outcomes among this population.
The Steiner tree problem is a classical NP-hard optimization problem with a wide range of practical applications. In an instance of this problem, we are given an undirected graph G = (V, E), a set of terminals R ⊆ V , and non-negative costs c e for all edges e ∈ E. Any tree that contains all terminals is called a Steiner tree; the goal is to find a minimum-cost Steiner tree. The nodes V \R are called Steiner nodes.The best approximation algorithm known for the Steiner tree problem is due to Robins and Zelikovsky (SIAM J. Discrete Math, 2005); their greedy algorithm achieves a performance guarantee of 1 + ln 3 2 ≈ 1.55. The best known linear programming (LP)-based algorithm, on the other hand, is due to Goemans and Bertsimas (Math. Programming, 1993) and achieves an approximation ratio of 2 − 2/|R|. In this paper we establish a link between greedy and LP-based approaches by showing that Robins and Zelikovsky's algorithm has a natural primal-dual interpretation with respect to a novel partition-based linear programming relaxation. We also exhibit surprising connections between the new formulation and existing LPs and we show that the new LP is stronger than the bidirected cut formulation.An instance is b-quasi-bipartite if each connected component of G\R has at most b vertices. We show that Robins' and Zelikovsky's algorithm has an approximation ratio better than 1 + ln 3 2 for such instances, and we prove that the integrality gap of our LP is between 8 7 and 2b+1 b+1 . Greedy algorithms and r-Steiner treesOne of the first approximation algorithms for the Steiner tree problem is the well-known minimum-spanning tree heuristic which is widely attributed to Moore [14]. Moore's algorithm has a performance ratio of 2 for the Steiner tree problem and this remained the best known until the 1990s, when Zelikovsky [41] suggested computing Steiner trees with a special structure, so called r-Steiner trees. Nearly all of the Steiner tree algorithms developed since then use r-Steiner trees. We now provide a formal definition.
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