I report a model for the formation of Saturn's family of mid-sized icy moons to coincide with the first flypast of Rhea by the Cassini spacecraft on 2005 November 26. It is proposed that the moons had condensed from a concentric family of orbiting gas rings that were shed some 4.6 × 109 yr ago by the proto-Saturnian (hereafter p-Sat) cloud. The p-Sat cloud is made up of gas and residual grains of the gas ring that was shed by the proto-Solar cloud (hereafter PSC) at Saturn's orbit. The bulk of the condensate within this proto-Solar ring accumulates to form Saturn's central core of mass ∼10–20 M ⊕ (M ⊕ = Earth mass). The process of formation of Saturn's solid core thus provides an opportunity for the p-Sat cloud to become depleted in rock and water ice relative to the usual solar abundances of these materials. Nitrogen, which exists as uncondensing N2 in the PSC and as NH3 in the p-Sat cloud, retains its solar abundance relative to H2. If the depletion factor of solids relative to gas is ζ dep = 0.25, as suggested by the low mass of Rhea relative to solar abundance expectations, the mass-percent ratio of NH3 to H2O in the dense p-Sat cloud is 36:64. Numerical and structural models for Rhea are constructed on the basis of a ‘cosmogonic’ bulk chemical composition of hydrated rock (mass fraction 0.385), H2O ice (0.395), and NH3 ice (0.220). It is difficult to construct a chemically differentiated model of Rhea whose mean density matches the observed value ρ Rhea = 1.23 ± 0.02 g cm−3 for reasonable bounds of the controlling parameters. Chemically homogeneous models can, however, be constrained to match the observed Rhea density provided that the mass fraction of NH3 is permitted to exceed the cosmogonic value by a factor ζ NH3 = 1.20–1.35. A large proportion of NH3 in the ice mass inhibits the formation of the dense crystalline phase II of H2O ice at high pressure. This may explain the lack of compressional features on the surface of the satellite that are expected as a result of ice II formation in the cooling core. The favoured model of Rhea is chemically uniform and has mass proportions of rock (0.369), H2O ice (0.378), and NH3 ice (0.253). The enhancement factor of NH3 lies within the measured uncertainties of the solar abundance of nitrogen. The satellite is very cold and nearly isodense. The predicted axial moment-of-inertia coefficient is [C/MR 2]Rhea = 0.399 ± 0.004.

Secondary postpartum haemorrhage is defined as any abnormal or excessive bleeding from the birth canal occurring between 24 hours and up to 12 weeks postpartum. The quantity of blood loss that constitutes secondary postpartum bleeding, unlike primary postpartum hemorrhage, is not clearly defined. Subjective estimation of the amount of blood loss constituting ‘haemorrhage’ accounts for at least some of the variation in reported incidence of secondary postpartum haemorrhage from 0.47% to 2%

Evidence is growing for the long-term effects of environmental factors during early-life on later disease susceptibility. It is believed that epigenetic mechanisms (changes in gene function not mediated by DNA sequence alteration), particularly DNA methylation, play a role in these processes. This paper reviews the current state of knowledge of the involvement of C1 metabolism and methyl donors and cofactors in maternal diet-induced DNA methylation changes in utero as an epigenetic mechanism. Methyl groups for DNA methylation are mostly derived from the diet and supplied through C1 metabolism by way of choline, betaine, methionine or folate, with involvement of riboflavin and vitamins B6 and B12 as cofactors. Mouse models have shown that epigenetic features, for example DNA methylation, can be altered by periconceptional nutritional interventions such as folate supplementation, thereby changing offspring phenotype. Evidence of early nutrient-induced epigenetic change in human subjects is scant, but it is known that during pregnancy C1 metabolism has to cope with high fetal demands for folate and choline needed for neural tube closure and normal development. Retrospective studies investigating the effect of famine or season during pregnancy indicate that variation in early environmental exposure in utero leads to differences in DNA methylation of offspring. This may affect gene expression in the offspring. Further research is needed to examine the real impact of maternal nutrient availability on DNA methylation in the developing fetus.

Few researchers would dispute that the pandemic of obesity is caused by a profound mismatch between humanity's present environmental circumstances and those that have moulded evolutionary selection. This concept was first articulated when gestational diabetes was described as being the result of a ‘thrifty genotype rendered detrimental by progress’. More recently, this hypothesis has been extended to the concept of a ‘thrifty phenotype’ to describe the metabolic adaptations adopted as a survival strategy by a malnourished fetus; changes that may also be inappropriate to deal with a later life of affluence. Both the thrifty genotype and the thrifty phenotype hypotheses would predict that populations in some areas of the developing world would be at greater risk of obesity and its co-morbidities; a proposition to be explored in the present paper. To date thrifty genes remain little more than a nebulous concept propagated by the intuitive logic that man has been selected to survive episodic famine and seasonal hungry periods. Under such conditions those individuals who could lay down extra energy stores and use them most efficiently would have a survival advantage. The search for candidate thrifty genes needs to cover every aspect of human energy balance from food-seeking behaviour to the coupling efficiency of oxidative phosphorylation. The present paper will describe examples of attempts to find thrifty genes in three selected candidate areas: maternally-transmitted mitochondrial genes; the uncoupling proteins; apoE4, whose geographical distribution has been linked to a possible thrifty role in lipoprotein and cholesterol metabolism.

In rural Gambia the risk of mainly infection-related mortality is 10-fold higher for adults born in the nutritionally-debilitating ‘hungry’ season, suggesting that immune function may be compromised by events early in life. The current programme of research focuses on the biological mechanisms underlying this hypothesis, exploring early-life environmental influences on immune development and the long-term functional consequences these influences may have. Results obtained to date show that thymus development during infancy is critically sensitive to environmental exposures, with smaller thymuses observed in the hungry season. Measurement of the frequency of T-cell receptor excision circles indicate that thymus function is also sensitive to seasonal influences, with further studies implicating variations in breast-milk IL-7 as a possible mediator of these effects. Studies in adults have shown that size at birth is positively correlated with antibody responses to vaccination with polysaccharide antigens, thus providing evidence for long-term functional deficits. The present paper will review progress made to date within this field of research.

This background paper considers the extent to which the development of new recommendations for dietary energy requirements needs to account for the macronutrient (fat, carbohydrate, protein and alcohol) profiles of different diets. The issues are discussed from the dual perspectives of avoiding under-nutrition and obesity. It is shown that, in practice, human metabolic processes can adapt to a wide range of fuel supply by altering fuel selection. It is concluded that, at the metabolic level, only diets with the most extreme macronutrient composition would have any consequences by exceeding the natural ability to modify fuel selection. However, diets of different macronutrient composition and energy density can have profound implications for innate appetite regulation and hence overall energy consumption.

The disease risk indicator plasma total homocysteine (tHcy) is influenced by genetic and environmental factors, including folate and vitamin B12 status. Little is known about the determinants of tHcy in rural West Africa. We explored the hypothesis that tHcy in rural Gambian adults might vary between the sexes and physiological groups, an/r with folate and vitamin B12 status. Comparisons were made with a British national survey. Non-pregnant Gambian women (n 158) had tHcy concentrations (geometric mean 9·0μmo/) similar to those of non-pregnant UK women (n 449; 9·4μmo/), whereas pregnant Gambian women (n 12) had significantly lower values (6·2μmo/). Gambian men (n 22) had significantly higher values (14·7μmo/) than British men (n 354; 10·8μmo/). Gambian lactating women and British men and women exhibited significant inverse relationships between loge(tHcy) and folate status; however, only the British subjects exhibited significant inverse relationships between loge(tHcy) and vitamin B12 status. In the British sample, and in Gambian lactating women, folate and vitamin B12 status variations together accounted for 20–25% of the variation in loge(tHcy). Within the UK, black-skinned adults had folate and tHcy levels similar to those of their white-skinned counterparts, but significantly higher vitamin B12 values. We conclude that, whereas folate and vitamin B12 status are similar between British and rural Gambian populations, tHcy is higher in Gambian men and lower in pregnant Gambian women, and that serum vitamin B12 values appear to be higher in black-skinned than white-skinned British subjects. Possible reasons are discussed.

A new model for the origin and bulk chemical composition of the inner planets, especially for their water content, is reported.

The origin of Mercury’s high metal content is examined within a gas ring model for the condensation of the planetary system. Mercury’s axial moment-of-inertia factor is predicted to be 0.325 ± 0.002.

The observed distribution of trans-Neptunian objects (TNOs) implies that they originally orbited in a narrow ring of radius 41 AU. The mass of the largest TNO was around 1 — 4 x 1026 g.