The socioeconomic dynamics of trends in female genital mutilation/cutting across Africa

Background The majority of women who undergo female genital mutilation/cutting (FGM/C) live in Africa. Although the UN Sustainable Development Goals call for intensified efforts to accelerate the abandonment of FGM/C, little is known about where in Africa the declines in prevalence have been fastest and whether changes in prevalence differ by women's socioeconomic status. Methods We use data from Demographic and Health Surveys and Multiple Indicator Cluster Surveys for 23 African countries, collected between 2002 and 2016, and covering 293 170 women. We reconstruct long-term cohort trends in FGM/C prevalence spanning 35 years, for women born between 1965 and 1999. We compute absolute and relative changes in FGM/C prevalence and differentials in prevalence by women's education and urban-rural residence. We examine whether socioeconomic differences in FGM/C are converging or diverging. Findings FGM/C prevalence has declined fastest (in relative terms) in countries with lower initial prevalence, and more slowly in countries with higher initial prevalence. Although better-educated women and those living in urban areas tend to have lower prevalence, in some countries the opposite pattern is observed. Socioeconomic differentials in FGM/C have grown in the majority of countries, particularly in countries with moderate-to-higher overall prevalence. Conclusions The documented relationship between absolute and relative FGM/C prevalence rates suggests that in settings with higher initial prevalence, FGM/C practice is likely to be more entrenched and to change more slowly. There is substantial variation between countries in socioeconomic differentials in prevalence and their changes over time. As countries change from higher to lower overall prevalence, socioeconomic inequalities in FGM/C are increasing

Female genital mutilation/cutting across Africa: dynamics of change and socioeconomic variation

Background: The majority of women who undergo female genital mutilation/cutting (FGM/C) live in Africa. Although the UN Sustainable Development Goals call for intensified efforts to accelerate the abandonment of FGM/C, little is known about where in Africa the declines in prevalence have been fastest and whether changes in prevalence differ by women’s socioeconomic status. Methods: We use data from Demographic and Health Surveys and Multiple Indicator Cluster Surveys for 23 African countries, collected between 2005 and 2015, and covering 293,170 women. We reconstruct long-term trends in FGM/C prevalence spanning 35 years. We compute absolute and relative rates of change in FGM/C prevalence and differentials in prevalence by women’s education and urban-rural residence. We examine whether socioeconomic differences in FGM/C are converging or diverging. Findings: FGM/C prevalence has declined fastest (in relative terms) in countries with lower initial prevalence, and more slowly in countries with higher initial prevalence. Although better-educated women and those living in urban areas tend to have lower prevalence, in some countries the opposite pattern is observed. Socioeconomic differentials in FGM/C have grown in the majority of countries, particularly in countries with moderate-to-higher overall prevalence. Conclusions: The documented relationship between absolute and relative FGM/C prevalence rates suggests that in settings with higher initial prevalence, FGM/C practice is likely to be more entrenched and to change more slowly. There is substantial variation between countries in socioeconomic differentials in prevalence and their changes over time. As countries change from higher to lower overall prevalence, socioeconomic inequalities in FGM/C are increasing

LIKE IN SIMILES – A RELEVANCE-THEORETIC VIEW

The paper examines the meaning of like as used in similes in the light of relevance theory. Similes, even though superficially indistinguishable from literal comparisons, are found to be closer to metaphors. Therefore, it is proposed that like in similes is different from like employed in literal comparisons. In particular, it is claimed that, contrary to the current relevance-theoretic position on this issue, like in similes introduces an ad hoc concept. This like is seen as both conceptual and procedural and, as such, it is distinct from both the conceptual like used in literal comparisons and the procedural like functioning as a pragmatic marker. Such a solution accounts for the similarities and differences between similes, metaphors and literal comparisons

Modelling radiation-induced cell cycle delays

Ionizing radiation is known to delay the cell cycle progression. In particular after particle exposure significant delays have been observed and it has been shown that the extent of delay affects the expression of damage such as chromosome aberrations. Thus, to predict how cells respond to ionizing radiation and to derive reliable estimates of radiation risks, information about radiation-induced cell cycle perturbations is required. In the present study we describe and apply a method for retrieval of information about the time-course of all cell cycle phases from experimental data on the mitotic index only. We study the progression of mammalian cells through the cell cycle after exposure. The analysis reveals a prolonged block of damaged cells in the G2 phase. Furthermore, by performing an error analysis on simulated data valuable information for the design of experimental studies has been obtained. The analysis showed that the number of cells analyzed in an experimental sample should be at least 100 to obtain a relative error less than 20%.Comment: 19 pages, 11 figures, accepted for publication in Radiation and Environmental Biophysic

Pubertal presentation in seven patients with congenital adrenal hyperplasia due to P450 Oxidoreductase deficiency

Context: P450 oxidoreductase (POR) is a crucial electron donor to all microsomal P450 cytochrome (CYP) enzymes including 17α-hydroxylase (CYP17A1), 21-hydroxylase (CYP21A2) and P450 aromatase. Mutant POR causes congenital adrenal hyperplasia with combined glucocorticoid and sex steroid deficiency. P450 oxidoreductase deficiency (ORD) commonly presents neonatally, with disordered sex development in both sexes, skeletal malformations, and glucocorticoid deficiency. \ud \ud Objective: The aim of the study was to describe the clinical and biochemical characteristics of ORD during puberty. \ud \ud Design: Clinical, biochemical, and genetic assessment of seven ORD patients (five females, two males) presenting during puberty was conducted. \ud \ud Results: Predominant findings in females were incomplete pubertal development (four of five) and large ovarian cysts (five of five) prone to spontaneous rupture, in some only resolving after combined treatment with estrogen/progestin, GnRH superagonists, and glucocorticoids. Pubertal development in the two boys was more mildly affected, with some spontaneous progression. Urinary steroid profiling revealed combined CYP17A1 and CYP21A2 deficiencies indicative of ORD in all patients; all but one failed to mount an appropriate cortisol response to ACTH stimulation indicative of adrenal insufficiency. Diagnosis of ORD was confirmed by direct sequencing, demonstrating disease-causing POR mutations. \ud \ud Conclusion: Delayed and disordered puberty can be the first sign leading to a diagnosis of ORD. Appropriate testosterone production during puberty in affected boys but manifest primary hypogonadism in girls with ORD may indicate that testicular steroidogenesis is less dependent on POR than adrenal and ovarian steroidogenesis. Ovarian cysts in pubertal girls may be driven not only by high gonadotropins but possibly also by impaired CYP51A1-mediated production of meiosis-activating sterols due to mutant POR

Discovery of a Dynamical Cold Point in the Heart of the Sagittarius dSph Galaxy with Observations from the APOGEE Project

The dynamics of the core of the Sagittarius (Sgr) dwarf spheroidal (dSph) galaxy are explored using high-resolution (R~22,500), H-band, near-infrared spectra of over 1,000 giant stars in the central 3 deg^2 of the system, of which 328 are identified as Sgr members. These data, among some of the earliest observations from the SDSS-III/Apache Point Observatory Galactic Evolution Experiment (APOGEE) and the largest published sample of high resolution Sgr dSph spectra to date, reveal a distinct gradient in the velocity dispersion of Sgr from 11-14 km/s for radii >0.8 degrees from center to a dynamical cold point of 8 km/s in the Sgr center --- a trend differing from that found in previous kinematical analyses of Sgr over larger scales that suggest a more or less flat dispersion profile at these radii. Well-fitting mass models with either cored and cusped dark matter distributions can be found to match the kinematical results, although the cored profile succeeds with significantly more isotropic stellar orbits than required for a cusped profile. It is unlikely that the cold point reflects an unusual mass distribution. The dispersion gradient may arise from variations in the mixture of populations with distinct kinematics within the dSph; this explanation is suggested (e.g., by detection of a metallicity gradient across similar radii), but not confirmed, by the present data. Despite these remaining uncertainties about their interpretation, these early test data (including some from instrument commissioning) demonstrate APOGEE's usefulness for precision dynamical studies, even for fields observed at extreme airmasses.Comment: 15 pages, 3 figure

Exploring Variation and Predictors of Residential Fine Particulate Matter Infiltration

Although individuals spend the majority of their time indoors, most epidemiological studies estimate personal air pollution exposures based on outdoor levels. This almost certainly results in exposure misclassification as pollutant infiltration varies between homes. However, it is often not possible to collect detailed measures of infiltration for individual homes in large-scale epidemiological studies and thus there is currently a need to develop models that can be used to predict these values. To address this need, we examined infiltration of fine particulate matter (PM2.5) and identified determinants of infiltration for 46 residential homes in Toronto, Canada. Infiltration was estimated using the indoor/outdoor sulphur ratio and information on hypothesized predictors of infiltration were collected using questionnaires and publicly available databases. Multiple linear regression was used to develop the models. Mean infiltration was 0.52 ± 0.21 with no significant difference across heating and non-heating seasons. Predictors of infiltration were air exchange, presence of central air conditioning, and forced air heating. These variables accounted for 38% of the variability in infiltration. Without air exchange, the model accounted for 26% of the variability. Effective modelling of infiltration in individual homes remains difficult, although key variables such as use of central air conditioning show potential as an easily attainable indicator of infiltration

Insights From Liver-Humanized Mice on Cholesterol Lipoprotein Metabolism and LXR-Agonist Pharmacodynamics in Humans

Background and Aims Genetically modified mice have been used extensively to study human disease. However, the data gained are not always translatable to humans because of major species differences. Liver-humanized mice (LHM) are considered a promising model to study human hepatic and systemic metabolism. Therefore, we aimed to further explore their lipoprotein metabolism and to characterize key hepatic species-related, physiological differences. Approach and Results Fah(-/-), Rag2(-/-), and Il2rg(-/-) knockout mice on the nonobese diabetic (FRGN) background were repopulated with primary human hepatocytes from different donors. Cholesterol lipoprotein profiles of LHM showed a human-like pattern, characterized by a high ratio of low-density lipoprotein to high-density lipoprotein, and dependency on the human donor. This pattern was determined by a higher level of apolipoprotein B100 in circulation, as a result of lower hepatic mRNA editing and low-density lipoprotein receptor expression, and higher levels of circulating proprotein convertase subtilisin/kexin type 9. As a consequence, LHM lipoproteins bind to human aortic proteoglycans in a pattern similar to human lipoproteins. Unexpectedly, cholesteryl ester transfer protein was not required to determine the human-like cholesterol lipoprotein profile. Moreover, LHM treated with GW3965 mimicked the negative lipid outcomes of the first human trial of liver X receptor stimulation (i.e., a dramatic increase of cholesterol and triglycerides in circulation). Innovatively, LHM allowed the characterization of these effects at a molecular level. Conclusions LHM represent an interesting translatable model of human hepatic and lipoprotein metabolism. Because several metabolic parameters displayed donor dependency, LHM may also be used in studies for personalized medicine.Peer reviewe

A geochronological review of magmatism along the external margin of Columbia and in the Grenville-age orogens forming the core of Rodinia

A total of 4344 magmatic U-Pb ages in the range 2300 to 800 Ma have been compiled from the Great Proterozoic Accretionary Orogen along the margin of the Columbia / Nuna supercontinent and from the subsequent Grenvillian collisional orogens forming the core of Rodinia. The age data are derived from Laurentia (North America and Greenland, n = 1212), Baltica (NE Europe, n = 1922), Amazonia (central South America, n = 625), Kalahari (southern Africa and Dronning Maud Land in East Antarctica, n = 386), and western Australia (n = 199). Laurentia, Baltica, and Amazonia (and possibly other cratons) most likely formed a ca. 10 000-km-long external active continental margin of Columbia from its assembly at ca. 1800 Ma until its dispersal at ca. 1260 Ma, after which all cratons studied were involved in the Rodinia-forming Grenvillian orogeny. However, the magmatic record is not smooth and even but highly irregular, with marked peaks and troughs, both for individual cratons and the combined data set. Magmatic peaks typically range in duration from a few tens of million years up to around hundred million years, with intervening troughs of comparable length. Some magmatic peaks are observed on multiple cratons, either by coincidence or because of paleogeographic proximity and common tectonic setting, while others are not. The best overall correlation, 0.617, is observed between Baltica and Amazonia, consistent with (but not definitive proof of) their being close neighbours in a SAMBA-like configuration at least in Columbia, and perhaps having shared the same peri-Columbian subduction system for a considerable time. Correlation factors between Laurentia and Baltica, or Laurentia and Amazonia, are below 0.14. Comparison between the Grenville Province in northeastern Laurentia and the Sveconorwegian Province in southwestern Fennoscandia (Baltica) shows some striking similarities, especially in the Mesoproterozoic, but also exhibits differences in the timing of events, especially during the final Grenville-Sveconorwegian collision, when the Sveconorwegian evolution seems to lag behind by some tens of million years. Between the other cratons, the evolution before and during the final Grenvillian collision is also largely diachronous. After 900 Ma, magmatic activity had ceased in all areas investigated, attesting to the position of most of them within the stable interior of Rodinia.publishedVersio