Previous observational studies suggested that vitamin D may control the absorption of iron (Fe) by inhibition of hepcidin, but the causal relevance of these associations is uncertain. Using placebo-controlled randomisation, we assessed the effects of supplementation with vitamin D on biochemical markers of Fe status and erythropoiesis in community-dwelling older people living in the UK. The BEST-D trial, designed to establish the optimum dose of vitamin D3 for future trials, had 305 participants, aged 65 years or older, randomly allocated to 4000 IU vitamin D3 (n 102), 2000 IU vitamin D3 (n 102) or matching placebo (n 101). We estimated the effect of vitamin D allocation on plasma levels of hepcidin, soluble transferrin receptor (sTfR), ferritin, Fe, transferrin, saturated transferrin (TSAT%) and the sTfR–ferritin index. Despite increases in 25-hydroxy-vitamin D, neither dose had significant effects on biochemical markers of Fe status or erythropoiesis. Geometric mean concentrations were similar in vitamin D3 arms v. placebo for hepcidin (20·7 [se 0·90] v. 20·5 [1·21] ng/ml), sTfR (0·69 [0·010] v. 0·70 [0·015] µg/ml), ferritin (97·1 [2·81] v. 97·8 [4·10] µg/l) and sTfR–ferritin ratio (0·36 [0·006] v. 0·36 [0·009]), respectively, while arithmetic mean levels were similar for Fe (16·7 [0·38] v. 17·3 [0·54] µmol/l), transferrin (2·56 [0·014] v. 2·60 [0·021] g/dl) and TSAT% (26·5 [0·60] v. 27·5 [0·85]). The proportions of participants with ferritin < 15 µg/l and TSAT < 16 % were unaltered by vitamin D3 suggesting that 12 months of daily supplementation with moderately high doses of vitamin D3 are unlikely to alter the Fe status of older adults.

Female fertility is a complex trait with age-specific changes in spontaneous dizygotic (DZ) twinning and fertility. To elucidate factors regulating female fertility and infertility, we conducted a genome-wide association study (GWAS) on mothers of spontaneous DZ twins (MoDZT) versus controls (3273 cases, 24,009 controls). This is a follow-up study to the Australia/New Zealand (ANZ) component of that previously reported (Mbarek et al., 2016), with a sample size almost twice that of the entire discovery sample meta-analysed in the previous article (and five times the ANZ contribution to that), resulting from newly available additional genotyping and representing a significant increase in power. We compare analyses with and without male controls and show unequivocally that it is better to include male controls who have been screened for recent family history, than to use only female controls. Results from the SNP based GWAS identified four genomewide significant signals, including one novel region, ZFPM1 (Zinc Finger Protein, FOG Family Member 1), on chromosome 16. Previous signals near FSHB (Follicle Stimulating Hormone beta subunit) and SMAD3 (SMAD Family Member 3) were also replicated (Mbarek et al., 2016). We also ran the GWAS with a dominance model that identified a further locus ADRB2 on chr 5. These results have been contributed to the International Twinning Genetics Consortium for inclusion in the next GWAS meta-analysis (Mbarek et al., in press).

Nutrition during the periconceptional period influences postnatal cardiovascular health. We determined whether in vitro embryo culture and transfer, which are manipulations of the nutritional environment during the periconceptional period, dysregulate postnatal blood pressure and blood pressure regulatory mechanisms. Embryos were either transferred to an intermediate recipient ewe (ET) or cultured in vitro in the absence (IVC) or presence of human serum (IVCHS) and a methyl donor (IVCHS+M) for 6 days. Basal blood pressure was recorded at 19–20 weeks after birth. Mean arterial pressure (MAP) and heart rate (HR) were measured before and after varying doses of phenylephrine (PE). mRNA expression of signaling molecules involved in blood pressure regulation was measured in the renal artery. Basal MAP did not differ between groups. Baroreflex sensitivity, set point, and upper plateau were also maintained in all groups after PE stimulation. Adrenergic receptors alpha-1A (αAR1A), alpha-1B (αAR1B), and angiotensin II receptor type 1 (AT1R) mRNA expression were not different from controls in the renal artery. These results suggest there is no programmed effect of ET or IVC on basal blood pressure or the baroreflex control mechanisms in adolescence, but future studies are required to determine the impact of ET and IVC on these mechanisms later in the life course when developmental programming effects may be unmasked by age.

This article responds to a variety of criticisms of our thesis that the longue durée is returning after a period of retreat, and that this return provides a necessary means to revive the discipline of history as a critical human science. We argue that the longue durée has different meanings in distinct historical traditions and that its importance for non-academic audiences will not be the same as for an academic readership. We also suggest that the longue durée should be combined with other historical time-scales (including those covered by microhistory), and that this combination can help us all to better understand the present in light of the past and then orient ourselves toward the future. In sum, we argue that the revenant longue durée can be one means, among others, to address the widespread “crisis of the humanities” that has been discerned by scholars around the world.