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OBJECTIVE Data regarding low maternal hemoglobin concentration and severe maternal morbidity (SMM) are limited and potentially biased. This study evaluated the relation between early maternal hemoglobin concentration and SMM or maternal mortality. DESIGN Population-based cohort study. SETTING Ontario, Canada, in a public healthcare system. POPULATION 737,393 births with a routine outpatient hemoglobin measured at a calculated gestational age of 2-16 weeks. METHODS The relation between early-pregnancy outpatient blood hemoglobin concentration and each study outcome was expressed as adjusted relative risks (aRR) and absolute risk differences (aRD), with 95% confidence intervals (CI), generated by modified Poisson regression. Main Outcome Measures The primary outcome was SMM or maternal mortality, from 23 weeks’ gestation to 42 days postpartum. RESULTS The mean (SD) hemoglobin concentration was 126.9 (9.3) g/L. Overall, SMM or death occurred in 13,514 pregnancies (1.8%). Relative to a hemoglobin of 125-129 g/L, the aRR was 1.07 (95% CI 1.02-1.13) and aRD (0.09%, 95% CI 0.01-0.18) at 120-124 g/L; aRR 1.31 (95% CI 1.17-1.46) and aRD 0.47% (95% CI 0.24-0.69) at 105-109 g/L; and aRR 4.53 (95% CI 3.59-5.72) and aRD 5.94% (95% CI 4.12-7.76) at less then 90 g/L. 5961 women (0.8%) required red cell transfusion, with significantly higher risks at all hemoglobin concentrations below 125-129 g/L, peaking at a hemoglobin less then 90 g/L (aRR 11.82, 95% CI 9.30-15.03). CONCLUSION There is a gradual increase in the risk of SMM or death, as well as red cell transfusion, starting from the lower level of the normal range of hemoglobin of non-pregnant women. This article is protected by copyright. All rights reserved.Senescence is a stable growth arrest that impairs the replication of damaged, old or preneoplastic cells, therefore contributing to tissue homeostasis. Senescent cells accumulate during ageing and are associated with cancer, fibrosis and many age-related pathologies. Recent evidence suggests that the selective elimination of senescent cells can be effective on the treatment of many of these senescence-associated diseases. A universal characteristic of senescent cells is that they display elevated activity of the lysosomal β-galactosidase, and this has been exploited as a marker for senescence (senescence-associated β-galactosidase activity). PX-478 order Consequently, we hypothesized that galactose-modified cytotoxic prodrugs will be preferentially processed by senescent cells, resulting in their selective killing. Here, we show that different galactose-modified duocarmycin (GMD) derivatives preferentially kill senescent cells. GMD prodrugs induce selective apoptosis of senescent cells in a lysosomal β-galactosidase (GLB1)-dependent manner. GMD prodrugs can eliminate a broad range of senescent cells in culture, and treatment with a GMD prodrug enhances the elimination of bystander senescent cells that accumulate upon whole-body irradiation treatment of mice. Moreover, taking advantage of a mouse model of adamantinomatous craniopharyngioma (ACP), we show that treatment with a GMD prodrug selectively reduced the number of β-catenin-positive preneoplastic senescent cells. In summary, the above results make a case for testing the potential of galactose-modified duocarmycin prodrugs to treat senescence-related pathologies. © 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.The front cover artwork is provided by the groups of Prof. Atanassov and Prof. Zenyuk (University of California Irvine, USA). The image shows rate-determining step of oxygen reduction reaction on platinum nanoparticle supported by carbon, which requires electron transfer but no proton. Read the full text of the Article at 10.1002/cphc.201901091. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.INTRODUCTION Minimal research has been conducted examining the relationship of positive psychology variables with quality of life (QOL) for individuals with bleeding disorders. While many individuals manage their bleeding disorders well, some are at higher risk of developing psychosocial complications due to the daily stressors of managing illness-related symptoms. AIM The purpose of this study is to better understand the relationships between two positive psychology variables, self-compassion and hope and QOL (overall, psychosocial and physical) among individuals diagnosed with bleeding disorders. METHODS Participants completed a survey identifying demographic information as well as rating scales of self-compassion, hope and quality of life. We conducted Pearson correlational and standard multiple regression analyses to explore the bivariate and linear relationships between the aforementioned variables in a sample of 86 patients with bleeding disorders between the ages of 15 and 65. RESULTS Self-compassion and hope were significantly related to QOL. Together, self-compassion and hope were predictive of overall QOL, psychosocial QOL and physical QOL. However, hope was the only individual predictor of all three QOL dimensions. CONCLUSION Due to the significant relationships found between self-compassion, hope and QOL in this sample, it may be beneficial to incorporate positive psychology factors into the treatment of those diagnosed with bleeding disorders, especially those at higher risk for decreased QOL. © 2020 John Wiley & Sons Ltd.Despite multiple studies, it has not been possible to account for the normal changes of blood pressure that occur from infancy to old age. We sought a comprehensive explanation, by linking brachial pressure with the well-documented changes in the arterial pulse waveform, whose peak and nadir determine systolic, diastolic, and pulse pressure in brachial arteries. Arterial pulse waveform changes in humans from birth throughout old age are readily explained on a) growth, with increasing length of the body from birth to adolescence, and adult height maintained thereafter, and b) degeneration and dilation of the aorta from elastic fibre fracture throughout life, causing progressive increase in aortic pressure wave amplitude from early return of wave reflection, and summation of incident with reflected waves in systole. Changes in arterial pulse waveforms throughout life complement and explain brachial cuff pressure values, with optimal pattern for cardiac interaction in adolescence. This article is protected by copyright.