Positive or Preventive?

This book adresses an important issue in historical demography - the differences between reproduction in low pressure and high pressure demographic regimes. The existence of such differences was first noted in 1789 by Thomas Malthus when he contrasted the low pressure European regimes with the high pressure regimes found in the less civilized parts of the world, most notably China and Japan. This contrast, long taken as fundamental by historical demographers, has recently been challenged by authors who argue that it should be discarded as Malthusian mythology. The papers included here evaluate the received and revisionist views by comparing reproduction in a high pressure regime - Taiwan during the Japanese occupation - and a low pressure regime - the Netherlands in the years 1830-1920. The papers examine the impact of infant mortality, social class, ethnic identity, illegitimacy, form of marriage, and rural vs. urban settings. Reality or mythology?, that is the question

Human biomonitoring in health risk assessment in Europe: Current practices and recommendations for the future.

Human biomonitoring (HBM) is an important tool to survey the internal exposure of humans which represents the real life chemical body burden to chemicals and/or their metabolites. It results from total exposure to chemical substances from different sources and via different routes. These substances may be regulated under different legislative frameworks on chemicals (e.g., environmental, occupational, food safety etc). In occupational health, HBM has long traditions to control the exposures at workplaces. By providing accurate data on internal exposure, HBM data can improve human health risk assessment (RA) for both the general population and workers. Although the past few years have shown good examples on the use of HBM in the RA of chemicals, there is still quite some work to be done to improve its use in a regulatory RA. Under the scope of the European Human Biomonitoring Initiative (project HBM4EU, 2017-2021), the current study reviews the state-of-the-art of HBM use in chemicals RA with a special focus in Europe, and attempts to identify hurdles and challenges faced by regulators. To gather information on the use of HBM, including the availability of guidance on how to use it in RA, the RA schemes applied by different European or international organizations were analysed. Examples of such use were identified for a few selected groups of chemicals of concern for human health. In addition, we present the results of a survey, aimed at collecting information from national regulatory risk assessors on their day-to-day RA practices, the use of HBM data, and the obstacles and challenges related to their use. The results evidenced and explained some of the current obstacles of using HBM data in RA. These included the lack of HBM guidance values or biomonitoring equivalents (BEs), limited toxicokinetic information to support the interpretation of HBM data and, in the occupational health and safety (OSH) field, the lack of legal enforcement. Therefore, to support the integration of HBM in regulatory RA, we recommend, on one hand, the elaboration of a EU level guidance on the use of HBM in RA and, on the other hand, the continuation of research efforts to integrate HBM with new RA approaches using in vitro/in silico data and Adverse Outcome Pathways (AOPs).This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 733032 HBM4EU, and received co-funding from the author's organizations. The authors thank to all other participants that contributed to this work.S

Organelle trafficking of chimeric ribozymes and genetic manipulation of mitochondria

With the expansion of the RNA world, antisense strategies have become widespread to manipulate nuclear gene expression but organelle genetic systems have remained aside. The present work opens the field to mitochondria. We demonstrate that customized RNAs expressed from a nuclear transgene and driven by a transfer RNA-like (tRNA-like) moiety are taken up by mitochondria in plant cells. The process appears to follow the natural tRNA import specificity, suggesting that translocation indeed occurs through the regular tRNA uptake pathway. Upon validation of the strategy with a reporter sequence, we developed a chimeric catalytic RNA composed of a specially designed trans-cleaving hammerhead ribozyme and a tRNA mimic. Organelle import of the chimeric ribozyme and specific target cleavage within mitochondria were demonstrated in transgenic tobacco cell cultures and Arabidopsis thaliana plants, providing the first directed knockdown of a mitochondrial RNA in a multicellular eukaryote. Further observations point to mitochondrial messenger RNA control mechanisms related to the plant developmental stage and culture conditions. Transformation of mitochondria is only accessible in yeast and in the unicellular alga Chlamydomonas. Based on the widespread tRNA import pathway, our data thus make a breakthrough for direct investigation and manipulation of mitochondrial genetics

The Atacama Cosmology Telescope: Detection of Patchy Screening of the Cosmic Microwave Background

Spatial variations in the cosmic electron density after reionization generate cosmic microwave background anisotropies via Thomson scattering, a process known as the ``patchy screening" effect. In this paper, we propose a new estimator for the patchy screening effect that is designed to mitigate biases from the dominant foreground signals. We use it to measure the cross-correlation between \textit{unWISE} galaxies and patchy screening, the latter measured by the Atacama Cosmology Telescope and \textit{Planck} satellite. We report the first detection of the patchy screening effect, with the statistical significance of the cross-correlation exceeding $7\sigma$. This measurement directly probes the distribution of electrons around these galaxies and provides strong evidence that gas is more extended than the underlying dark matter. By comparing our measurements to electron profiles extracted from simulations, we demonstrate the power of these observations to constrain galaxy evolution models. Requiring only the 2D positions of objects and no individual redshifts or velocity estimates, this approach is complementary to existing gas probes, such as those based on the kinetic Sunyaev-Zeldovich effect.Comment: See Schutt et al for a detailed comparison of patchy screening estimators. 17 pages with 8 figure

Ovarian stimulation for IVF and risk of primary breast cancer in BRCA1/2 mutation carriers

Background: The effect of in vitro fertilisation (IVF) on breast cancer risk for BRCA1/2 mutation carriers is rarely examined. As carriers may increasingly undergo IVF as part of preimplantation genetic diagnosis (PGD), we examined the impact of ovarian stimulation for IVF on breast cancer risk in BRCA1/2 mutation carriers. Methods: The study population consisted of 1550 BRCA1 and 964 BRCA2 mutation carriers, derived from the nationwide HEBON study and the nationwide PGD registry. Questionnaires, clinical records and linkages with the Netherlands Cancer Registry were used to collect data on IVF exposure, risk-reducing surgeries and cancer diagnosis, respectively. Time-dependent Cox regression analyses were conducted, stratified for birth cohort and adjusted for subfertility. Results: Of the 2514 BRCA1/2 mutation carriers, 3% (n = 76) were exposed to ovarian stimulation for IVF. In total, 938 BRCA1/2 mutation carriers (37.3%) were diagnosed with breast cancer. IVF exposure was not associated with risk of breast cancer (HR: 0.79, 95% CI: 0.46–1.36). Similar results were found for the subgroups of subfertile women (n = 232; HR: 0.73, 95% CI: 0.39–1.37) and BRCA1 mutation carriers (HR: 1.12, 95% CI: 0.60–2.09). In addition, age at and recency of first IVF treatment were not associated with breast cancer risk. Conclusion: No evidence was found for an association between ovarian stimulation for IVF and breast cancer risk in BRCA1/2 mutation carriers

The predictive ability of the 313 variant–based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant

Abstract: Purpose: To evaluate the association between a previously published 313 variant–based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes. Methods: We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk. Results: For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06–1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07–1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative PRS313 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively. Conclusion: The PRS313 can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS313 needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making

What the Seasons Tell Us. The Monthly Movement of Marriages, Economic Modernization, and Secularization in the Netherlands, 1810-1940

This study focuses on the seasonal pattern of marriages in seven provinces of the Netherlands from 1810 to 1940. We ask whether the prevalence of May as the preferred marriage month was dimin­ishing when industrialization changed the course of workload over the year. And if so, when did this occur, and were there differences between the regions? Given the ban on marriages during Lent and Advent, by studying the number of marriages during these months (approximated as March and De­cember), we can determine which provinces adhered most to the religious rules, and how this pattern developed over time. In doing so, we have an excellent demographic measure for secularization. The analysis is based on the LINKS dataset which currently includes almost 2 million marriages that were contracted in seven Dutch provinces: Groningen, Drenthe, Overijssel, Gelderland, Noord-Holland, Zeeland and Limburg. The main conclusion of this study is that although Dutch society substantially transformed (economically, socially, politically and culturally) during the 19th and early 20th centuries until the Second World War, it was both the agricultural calendar and the Roman Catholic regulations that determined Dutch marriage seasonality

De erfenis van Thomas Malthus betwist : een discussie over het kindertal in China en Europa

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