Natural enrichment of Cd and Tl in the bark of trees from a rural watershed devoid of point sources of metal contamination.

To help understand the bioaccumulation of Cd and Tl in beaver tissue, we examined the enrichment of these metals in vegetation available to the animals. Bark was collected from 40 species of trees and shrubs, along with a complete soil weathering profile, within a small watershed devoid of trace metal contamination. Weathering resulted in a 5x enrichment of Cd in the soils relative to the underlying sediments, and a 6x Tl depletion: while Cd was lost from calcite and accumulates in the organic matter and oxyhydroxide fractions, Tl occurred only in the residual fraction. Soil processes alone, however, cannot explain the anomalous concentrations and enrichments of Cd in willow and poplar which contain up to 8.5 mg/kg Cd. The concentrations of Cd and Tl in the dissolved fraction (<0.45 µm) of the Wye River are similar (1.2 ± 0.4 and 1.6 ± 0.1 ng/L, respectively), and are taken to estimate their bioavailability in soil solutions. Normalizing the Cd/metal ratios in bark to the corresponding ratios in water yields the Stream Enrichment Factor: this novel approach shows that all plant species are enriched in Cd relative to Ni; 33 relative to Cu, 13 relative to Zn, and 7 relative to Mn. Thus, many plants preferentially accumulate Cd, especially willow and poplar, over these essential micronutrients. Clearly, the enrichment of Cd over Tl in bark is not a reflection of differences in bioavailability, but rather on the preferential uptake of Cd by the plants. The profound natural bioaccumulation of Cd in the bark of willow and poplar, the two favourite foods of the beaver, has ramifications for the use of these aquatic mammals as biomonitors of environmental contamination, as well as for the direct and indirect consumption of bark for traditional food and medicine.

Mineral-nutrient relationships in African soils assessed using cluster analysis of X-ray powder diffraction patterns and compositional methods.

Soil mineral compositions are often complex and spatially diverse, with each mineral exhibiting characteristic chemical properties that determine the intrinsic total concentration of soil nutrients and their phyto-availability. Defining soil mineral-nutrient relationships is therefore important for understanding the inherent fertility of soils for sustainable nutrient management, and data-driven approaches such as cluster analysis allow for these relations to be assessed in new detail. Here the fuzzy-c-means clustering algorithm was applied to an X-ray powder diffraction (XRPD) dataset of 935 soils from sub-Saharan Africa, with each diffractogram representing a digital signature of a soil's mineralogy. Nine mineralogically distinct clusters were objectively selected from the soil mineralogy continuum by retaining samples exceeding the 75 % quantile of the membership coefficients in each cluster, yielding a dataset of 239 soils. As such, samples within each cluster represented mineralogically similar soils from different agro-ecological environments of sub-Saharan Africa. Mineral quantification based on the mean diffractogram of each cluster illustrated substantial mineralogical diversity between the nine groups with respect to quartz, K-feldspar, plagioclase, Fe/Al/Ti-(hydr)oxides, phyllosilicates (1:1 and 2:1), ferromagnesians, and calcite. Mineral-nutrient relationships were defined using the clustered XRPD patterns and corresponding measurements of total and/or extractable (Mehlich-3) nutrient concentrations (B, Mg, K, Ca, Mn, Fe, Ni, Cu and Zn) in combination with log-ratio compositional data analysis. Fe/Al/Ti/Mn-(hydr)oxides and feldspars were found to be the primary control of total nutrient concentrations, whereas 2:1 phyllosilicates were the main source of all extractable nutrients except for Fe and Zn. Kaolin minerals were the most abundant phyllosilicate group within the dataset but did not represent a nutrient source, which reflects the lack of nutrients within their chemical composition and their low cation exchange capacity. Results highlight how the mineral composition controls the total nutrient reserves and their phyto-availability in soils of sub-Saharan Africa. The typical characterisation of soils and their parent material based on the clay particle size fraction (i.e. texture) and/or the overall silica component (i.e. acid and basic rock types) alone may therefore mask the intricacies of mineral contributions to soil nutrient concentrations.

Pre-treatment of soil X-ray powder diffraction data for cluster analysis.

X-ray powder diffraction (XRPD) is widely applied for the qualitative and quantitative analysis of soil mineralogy. In recent years, high-throughput XRPD has resulted in soil XRPD datasets containing thousands of samples. The efforts required for conventional approaches of soil XRPD data analysis are currently restrictive for such large data sets, resulting in a need for computational methods that can aid in defining soil property - soil mineralogy relationships. Cluster analysis of soil XRPD data represents a rapid method for grouping data into discrete classes based on mineralogical similarities, and thus allows for sets of mineralogically distinct soils to be defined and investigated in greater detail. Effective cluster analysis requires minimisation of sample-independent variation and maximisation of sample-dependent variation, which entails pre-treatment of XRPD data in order to correct for common aberrations associated with data collection. A 24 factorial design was used to investigate the most effective data pre-treatment protocol for the cluster analysis of XRPD data from 12 African soils, each analysed once by five different personnel. Sample-independent effects of displacement error, noise and signal intensity variation were pre-treated using peak alignment, binning and scaling, respectively. The sample-dependent effect of strongly diffracting minerals overwhelming the signal of weakly diffracting minerals was pre-treated using a square-root transformation. Without pre-treatment, the 60 XRPD measurements failed to provide informative clusters. Pre-treatment via peak alignment, square-root transformation, and scaling each resulted in significantly improved partitioning of the groups (p < 0.05). Data pre-treatment via binning reduced the computational demands of cluster analysis, but did not significantly affect the partitioning (p > 0.1). Applying all four pre-treatments proved to be the most suitable protocol for both non-hierarchical and hierarchical cluster analysis. Deducing such a protocol is considered a prerequisite to the wider application of cluster analysis in exploring soil property - soil mineralogy relationships in larger datasets.

Geophagy among East African Chimpanzees: consumed soils provide protection from plant secondary compounds and bioavailable iron.

Geophagy, the intentional consumption of earth materials, has been recorded in humans and other animals. It has been hypothesized that geophagy is an adaptive behavior, and that clay minerals commonly found in eaten soil can provide protection from toxins and/or supplement micronutrients. To test these hypotheses, we monitored chimpanzee geophagy using camera traps in four permanent sites at the Budongo Forest Reserve, Uganda, from October 2015-October 2016. We also collected plants, and soil chimpanzees were observed eating. We analyzed 10 plant and 45 soil samples to characterize geophagic behavior and geophagic soil and determine (1) whether micronutrients are available from the soil under physiological conditions and if iron is bioavailable, (2) the concentration of phenolic compounds in plants, and (3) if consumed soils are able to adsorb these phenolics. Chimpanzees ate soil and drank clay-infused water containing 1:1 and 2:1 clay minerals and > 30% sand. Under physiological conditions, the soils released calcium, iron, and magnesium. In vitro Caco-2 experiments found that five times more iron was bioavailable from three of four soil samples found at the base of trees. Plant samples contained approximately 60 µg/mg gallic acid equivalent. Soil from one site contained 10 times more 2:1 clay minerals, which were better at removing phenolics present in their diet. We suggest that geophagy may provide bioavailable iron and protection from phenolics, which have increased in plants over the last 20 years. In summary, geophagy within the Sonso community is multifunctional and may be an important self-medicative behavior.

Soil eaten by chacma baboons adsorbs polar plant secondary metabolites representative of those found in their diet.

Geophagy, the deliberate consumption of earth materials, is common among humans and animals. However, its etiology and function(s) remain poorly understood. The major hypotheses about its adaptive functions are the supplementation of essential elements and the protection against temporary and chronic gastrointestinal (GI) distress. Because much less work has been done on the protection hypothesis, we investigated whether soil eaten by baboons protected their GI tract from plant secondary metabolites (PSMs) and described best laboratory practices for doing so. We tested a soil that baboons eat/preferred, a soil that baboons never eat/non-preferred, and two clay minerals, montmorillonite a 2:1 clay and kaolinite a 1:1 clay. These were processed using a technique that simulated physiological digestion. The phytochemical concentration of 10 compounds representative of three biosynthetic classes of compounds found in the baboon diet was then assessed with and without earth materials using high-performance liquid chromatography with diode-array detection (HPLC-DAD). The preferred soil was white, contained 1% halite, 45% illite/mica, 14% kaolinite, and 0.8% sand; the non-preferred soil was pink, contained 1% goethite and 1% hematite but no halite, 40% illite/mica, 19% kaolinite, and 3% sand. Polar phenolics and alkaloids were generally adsorbed at levels 10× higher than less polar terpenes. In terms of PSM adsorption, the montmorillonite was more effective than the kaolinite, which was more effective than the non-preferred soil, which was more effective than the preferred soil. Our findings suggest that HPLC-DAD is best practice for the assessment of PSM adsorption of earth materials due to its reproducibility and accuracy. Further, soil selection was not based on adsorption of PSMs, but on other criteria such as color, mouth feel, and taste. However, the consumption of earth containing clay minerals could be an effective strategy for protecting the GI tract from PSMs.

Phosphatase-mediated bioprecipitation of lead by soil fungi.

Geoactive soil fungi were examined for their ability to release inorganic phosphate (Pi ) and mediate lead bioprecipitation during growth on organic phosphate substrates. Aspergillus niger and Paecilomyces javanicus grew in 5 mM Pb(NO3)2-containing media amended with glycerol 2-phosphate (G2P) or phytic acid (PyA) as sole P sources, and liberated Pi into the medium. This resulted in almost complete removal of Pb from solution and extensive precipitation of lead-containing minerals around the biomass, confirming the importance of the mycelium as a reactive network for biomineralization. The minerals were identified as pyromorphite (Pb5(PO4)3Cl), only produced by P. javanicus, and lead oxalate (PbC2O4), produced by A. niger and P. javanicus. Geochemical modelling of lead and lead mineral speciation as a function of pH and oxalate closely correlated with experimental conditions and data. Two main lead biomineralization mechanisms were therefore distinguished: pyromorphite formation depending on organic phosphate hydrolysis and lead oxalate formation depending on oxalate excretion. This also indicated species specificity in biomineralization depending on nutrition and physiology. Our findings provide further understanding of lead geomycology and organic phosphates as a biomineralization substrate, and are also relevant to metal immobilization biotechnologies for bioremediation, metal and P biorecovery, and utilization of waste organic phosphates.

Uranium phosphate biomineralization by fungi.

Geoactive soil fungi were investigated for phosphatase-mediated uranium precipitation during growth on an organic phosphorus source. Aspergillus niger and Paecilomyces javanicus were grown on modified Czapek-Dox medium amended with glycerol 2-phosphate (G2P) as sole P source and uranium nitrate. Both organisms showed reduced growth on uranium-containing media but were able to extensively precipitate uranium and phosphorus-containing minerals on hyphal surfaces, and these were identified by X-ray powder diffraction as uranyl phosphate species, including potassium uranyl phosphate hydrate (KPUO6 .3H2 O), meta-ankoleite [(K1.7 Ba0.2 )(UO2 )2 (PO4 )2 .6H2 O], uranyl phosphate hydrate [(UO2 )3 (PO4 )2 .4H2 O], meta-ankoleite (K(UO2 )(PO4 ).3H2 O), uramphite (NH4 UO2 PO4 .3H2 O) and chernikovite [(H3 O)2 (UO2 )2 (PO4 )2 .6H2 O]. Some minerals with a morphology similar to bacterial hydrogen uranyl phosphate were detected on A. niger biomass. Geochemical modelling confirmed the complexity of uranium speciation, and the presence of meta-ankoleite, uramphite and uranyl phosphate hydrate between pH 3 and 8 closely matched the experimental data, with potassium as the dominant cation. We have therefore demonstrated that fungi can precipitate U-containing phosphate biominerals when grown with an organic source of P, with the hyphal matrix serving to localize the resultant uranium minerals. The findings throw further light on potential fungal roles in U and P biogeochemistry as well as the application of these mechanisms for element recovery or bioremediation.

Transformation of vanadinite [Pb5 (VO4 )3 Cl] by fungi.

Saprotrophic fungi were investigated for their bioweathering effects on the vanadium- and lead-containing insoluble apatite group mineral, vanadinite [Pb5 (VO4 )3 Cl]. Despite the insolubility of vanadinite, fungi exerted both biochemical and biophysical effects on the mineral including etching, penetration and formation of new biominerals. Lead oxalate was precipitated by Aspergillus niger during bioleaching of natural and synthetic vanadinite. Some calcium oxalate monohydrate (whewellite) was formed with natural vanadinite because of the presence of associated ankerite [Ca(Fe(2+) ,Mg)(CO3 )2 ]. Aspergillus niger also precipitated lead oxalate during growth in the presence of lead carbonate, vanadium(V) oxide and ammonium metavanadate, while abiotic tests confirmed the efficacy of oxalic acid in solubilizing vanadinite and precipitating lead as oxalate. Geochemical modelling confirmed the complexity of vanadium speciation, and the significant effect of oxalate. Oxalate-vanadium complexes markedly reduced the vanadinite stability field, with cationic lead(II) and lead oxalate also occurring. In all treatments and geochemical simulations, no other lead vanadate, or vanadium minerals were detected. This research highlights the importance of oxalate in vanadinite bioweathering and suggests a general fungal transformation of lead-containing apatite group minerals (e.g. vanadinite, pyromorphite, mimetite) by this mechanism. The findings are also relevant to remedial treatments for lead/vanadium contamination, and novel approaches for vanadium recovery.

Fungal Bioweathering of Mimetite and a General Geomycological Model for Lead Apatite Mineral Biotransformations.

Fungi play important roles in biogeochemical processes such as organic matter decomposition, bioweathering of minerals and rocks, and metal transformations and therefore influence elemental cycles for essential and potentially toxic elements, e.g., P, S, Pb, and As. Arsenic is a potentially toxic metalloid for most organisms and naturally occurs in trace quantities in soil, rocks, water, air, and living organisms. Among more than 300 arsenic minerals occurring in nature, mimetite [Pb5(AsO4)3Cl] is the most stable lead arsenate and holds considerable promise in metal stabilization for in situ and ex situ sequestration and remediation through precipitation, as do other insoluble lead apatites, such as pyromorphite [Pb5(PO4)3Cl] and vanadinite [Pb5(VO4)3Cl]. Despite the insolubility of mimetite, the organic acid-producing soil fungus Aspergillus niger was able to solubilize mimetite with simultaneous precipitation of lead oxalate as a new mycogenic biomineral. Since fungal biotransformation of both pyromorphite and vanadinite has been previously documented, a new biogeochemical model for the biogenic transformation of lead apatites (mimetite, pyromorphite, and vanadinite) by fungi is hypothesized in this study by application of geochemical modeling together with experimental data. The models closely agreed with experimental data and provided accurate simulation of As and Pb complexation and biomineral formation dependent on, e.g., pH, cation-anion composition, and concentration. A general pattern for fungal biotransformation of lead apatite minerals is proposed, proving new understanding of ecological implications of the biogeochemical cycling of component elements as well as industrial applications in metal stabilization, bioremediation, and biorecovery.

Pyromorphite formation in a fungal biofilm community growing on lead metal.

Lead is a priority pollutant, and lead metal is widely found in the environment as a waterproofing structural component in roofing, fence post covers, venting and flashing, as well as in industrial and urban waste. However, little is known of microbial interactions with metallic lead. The objective of this research was to investigate fungal roles in transformations of lead in a surface biofilm community growing on lead sheeting. The lead surface was found to support a diverse fungal community with several members, such as Aureobasidum pullulans, Phoma macrostoma, Penicillium sp. and Botryotinia fuckeliana, probably originating from adjacent phylloplane communities. Many fungal isolates showed tolerance to lead compounds in growth inhibition assays and were able to mediate production of lead-containing secondary minerals in the presence of metallic lead. These exhibited widely differing morphologies to the lead-containing secondary minerals produced under abiotic conditions. The presence of pyromorphite (Pb5 (PO4 )3 Cl) (approximately 50 wt%) was detected in the lead sheet biofilm, and we speculate that animal (bird) faeces could be a significant source of phosphorus in this location. Pyromorphite formation represents biomineralization of mobile lead species into a very stable form, and this research provides the first demonstration of its occurrence in the natural environment.

Fungal biotransformation of zinc silicate and sulfide mineral ores.

In this work, several fungi with geoactive properties, including Aspergillus niger, Beauveria caledonica and Serpula himantioides, were used to investigate their potential bioweathering effects on zinc silicate and zinc sulfide ores used in zinc extraction and smelting, to gain understanding of the roles that fungi may play in transformations of such minerals in the soil, and effects on metal mobility. Despite the recalcitrance of these minerals, new biominerals resulted from fungal interactions with both the silicate and the sulfide, largely resulting from organic acid excretion. Zinc oxalate dihydrate was formed through oxalate excretion by the test fungi and the mineral surfaces showed varying patterns of bioweathering and biomineral formation. In addition, calcium oxalate was formed from the calcium present in the mineral ore fractions, as well as calcite. Such metal immobilization may indicate that the significance of fungi in effecting metal mobilization from mineral ores such as zinc silicate and zinc sulfide is rather limited, especially if compared with bacterial sulfide leaching. Nevertheless, important bioweathering activities of fungi are confirmed which could be of local significance in soils polluted by such materials, as well as in the mycorrhizosphere.

IVF endocrinology: the Edwards era.

Through pioneering human IVF as a global infertility treatment, Robert Edwards and his clinical partner Patrick Steptoe launched the field of IVF endocrinology. Following repeated failures with oocytes collected in human menopausal gonadotrophin (HMG) primed cycles timed to injection of human chorionic gonadotrophin (HCG), the first successful IVF pregnancy came from a spontaneous menstrual cycle. Intensive endocrine monitoring was used to track pre-ovulatory follicular development and collect a single ripe egg timed to the natural LH surge. Despite this groundbreaking achievement, ovulation induction was clearly required to make IVF treatment clinically robust and reliable. Ovarian stimulation with clomiphene citrate was used to achieve the first maternity from a superovulated human IVF cycle in 1980. HMG/HCG regimens were then successfully introduced-including substitution of 'pure' follicle-stimulating hormone as the principal ovarian stimulant. The application and success of IVF treatment were dramatically enhanced by the introduction of gonadotrophin-releasing hormone analogues that enabled elective control of endogenous gonadotrophin release during ovarian stimulation. Programmed gonadotrophin regimes yielding double-digit oocyte numbers became normal: 'more is better' was the ethos. Bob Edwards expressed increasing concern over the cost, complexity and potential long-term health risks of such high-order ovarian stimulation. In later life he repeatedly called for a return to minimalist approaches based on the natural menstrual cycle to improve oocyte quality over quantity. This article reviews the application of ovulation induction to human IVF and celebrates Edwards' abiding impact on the field, which firmly grounds him in the reproductive endocrinology pantheon.

Biotransformation of manganese oxides by fungi: solubilization and production of manganese oxalate biominerals.

The ability of the soil fungi Aspergillus niger and Serpula himantioides to tolerate and solubilize manganese oxides, including a fungal-produced manganese oxide and birnessite, was investigated. Aspergillus niger and S. himantioides were capable of solubilizing all the insoluble oxides when incorporated into solid medium: MnO(2) and Mn(2) O(3) , mycogenic manganese oxide (MnO(x) ) and birnessite [(Na(0.3) Ca(0.1) K(0.1) )(Mn(4+) ,Mn(3+) )(2) O(4) ·1.5H(2) O]. Manganese oxides were of low toxicity and A. niger and S. himantioides were able to grow on 0.5% (w/v) of all the test compounds, with accompanying acidification of the media. Precipitation of insoluble manganese and calcium oxalate occurred under colonies growing on agar amended with all the test manganese oxides after growth of A. niger and S. himantioides at 25°C. The formation of manganese oxalate trihydrate was detected after growth of S. himantioides with birnessite which subsequently was transformed to manganese oxalate dihydrate. Our results represent a novel addition to our knowledge of the biogeochemical cycle of manganese, and the roles of fungi in effecting transformations of insoluble metal-containing compounds in the environment.

Evidence that nuclear receptors are related to terpene synthases.

Ligand-activated nuclear receptors (NRs) orchestrate development, growth, and reproduction across all animal lifeforms - the Metazoa - but how NRs evolved remains mysterious. Given the NR ligands including steroids and retinoids are predominantly terpenoids, we asked whether NRs might have evolved from enzymes that catalyze terpene synthesis and metabolism. We provide evidence suggesting that NRs may be related to the terpene synthase (TS) enzyme superfamily. Based on over 10,000 3D structural comparisons, we report that the NR ligand-binding domain and TS enzymes share a conserved core of seven α-helical segments. In addition, the 3D locations of the major ligand-contacting residues are also conserved between the two protein classes. Primary sequence comparisons reveal suggestive similarities specifically between NRs and the subfamily of cis-isoprene transferases, notably with dehydrodolichyl pyrophosphate synthase and its obligate partner, NUS1/NOGOB receptor. Pharmacological overlaps between NRs and TS enzymes add weight to the contention that they share a distant evolutionary origin, and the combined data raise the possibility that a ligand-gated receptor may have arisen from an enzyme antecedent. However, our findings do not formally exclude other interpretations such as convergent evolution, and further analysis will be necessary to confirm the inferred relationship between the two protein classes.

Rapid extraction of high- and low-density microplastics from soil using high-gradient magnetic separation.

Microplastics (MPs) are present in all environments, and concerns over their possible detrimental effects on flora and fauna have arisen. Density separation (DS) is commonly used to separate MPs from soils to allow MP quantification; however, it frequently fails to extract high-density MPs sufficiently, resulting in under-estimation of MP abundances. In this proof-of-concept study, a novel three-stage extraction method was developed, involving high-gradient magnetic separation and removal of magnetic soil (Stage 1), magnetic tagging of MPs using surface modified iron nanoparticles (Stage 2), and high-gradient magnetic recovery of surface-modified MPs (Stage 3). The method was optimised for four different soil types (loam, high­carbon loamy sand, sandy loam and high-clay sandy loam) spiked with different MP types (polyethylene, polyethylene terephthalate, and polytetrafluoroethylene) of different particle sizes (63 µm to 2 mm) as well as polyethylene fibres (2-4 mm). The optimised method achieved average recoveries of 96% for fibres and 92% for particles in loam, 91% for fibres and 87% for particles in high­carbon loamy sand, 96% for fibres and 89% for particles in sandy loam, and 97% for fibres and 94% for particles in high-clay sandy loam. These were significantly higher than recoveries achieved by DS, particularly for fibres and high-density MPs (p < 0.05). To demonstrate the practical application of the HGMS method, it was applied to a farm soil sample, and high-density MP particles were only recovered by HGMS. Furthermore, this study showed that HGMS can recover fibre-aggregate complexes. This improved extraction method will provide better estimates of MP quantities in future studies focused on monitoring the prevalence of MPs in soils.

Micro and nano sized particles in leachates from agricultural soils: Phosphorus and sulfur speciation by X-ray micro-spectroscopy.

Colloids and nanoparticles leached from agricultural land are major carriers of potentially bioavailable nutrients with high mobility in the environment. Despite significant research efforts, accurate knowledge of macronutrients in colloids and nanoparticles is limited. We used multi-elemental synchrotron X-ray fluorescence (XRF) microscopy with multivariate spatial analysis and X-ray atomic absorption near-edge structure (XANES) spectroscopy at the P and S K-edges, to study the speciation of P and S in two fractions of leached particles, >0.45 and <0.45 µm respectively, collected from four tile-drained agricultural sites in Sweden. P K-edge XANES showed that organic P, followed by P adsorbed to surfaces of aluminum-bearing particles were the most common forms of leached P. Iron-bound P (Fe-P) forms were generally less abundant (0-30 % of the total P). S K-edge XANES showed that S was predominantly organic, and a relatively high abundance of reduced S species suggests that redox conditions were adverse to the persistence of P bound to Fe-bearing colloids in the leachates. Acid ammonium-oxalate extractions suggested that P associated with Al and Fe (Al-P and Fe-P) in most cases could be explained by the adsorption capacity of non-crystalline (oxalate-extractable) oxides of Al and Fe. These results improve our understanding of particulate P and S speciation in the vadose zone and helps in developing effective technologies for mitigating colloidal driven eutrophication of water bodies near agricultural land.

Low dose dexamethasone as treatment for women with heavy menstrual bleeding: A response-adaptive randomised placebo-controlled dose-finding parallel group trial (DexFEM).

BACKGROUND: The symptom of heavy menstrual bleeding (HMB) diminishes quality-of-life for many mid-age women and imposes substantial societal burden. We investigated our hypothesis that HMB reflects impaired endometrial vasoconstriction due to endometrial glucocorticoid deficiency. Does reversing this deficiency, by short-term luteal-phase treatment with exogenous glucocorticoid (dexamethasone), ameliorate HMB? METHODS: In our Bayesian response-adaptive parallel-group placebo-controlled randomised trial, five pre-planned interim analyses used primary outcome data to adjust randomisation probabilities to favour doses providing most dose-response information. Participants with HMB, recruited from Lothian (Scotland) NHS clinics and via community invitations/advertisements, were aged over 18 years; reported regular 21-42 day menstrual cycles; and had measured menstrual blood loss (MBL) averaging ≥ 50 mL over two screening periods. Identically encapsulated placebo, or one of six Dexamethasone doses (0·2 mg, 0·4 mg, 0·5 mg, 0·6 mg, 0·75 mg, 0·9 mg), were taken orally twice-daily over five days in the mid-luteal phase of three menstrual cycles. Participants, investigators, and those measuring outcomes were masked to group assignment. Primary outcome, change in average MBL from screening to 'treatment', was analysed by allocated treatment, for all with data. TRIAL REGISTRATION: ClinicalTrials.gov NCT01769820; EudractCT 2012-003,405-98 FINDINGS: Recruitment lasted 29/01/2014 to 25/09/2017; 176 were screened, 107 randomised and 97 provided primary outcome data (n = 24,5,9,21,8,14,16 in the seven arms, placebo to 1·8 mg total daily active dose). In Bayesian normal dynamic linear modelling, 1·8 mg dexamethasone daily showed a 25 mL greater reduction in MBL from screening, than placebo (95% credible interval 1 to 49 mL), and probability 0·98 of benefit over placebo. Adverse events were reported by 75% (58/77) receiving dexamethasone, 58% (15/26) taking placebo. Three serious adverse events occurred, two during screening, one in a placebo participant. No woman withdrew due to adverse effects. INTERPRETATION: Our adaptive trial in HMB showed that dexamethasone 1·8 mg daily reduced menstrual blood loss. The role of dexamethasone in HMB management deserves further investigation. FUNDING: UK MRC DCS/DPFS grant MR/J003611/1.

Differences and commonalities in physical, chemical and mineralogical properties of Zanzibari geophagic soils.

The function of human geophagy has long been questioned. We sought to test hypotheses concerning its potential physiological effects through analysis of soils and patterns in geophagy behavior. Eleven samples of geophagic soils consumed by pregnant women on Pemba Island, Zanzibar, Tanzania, were characterized according to their color, texture, major element chemistry, trace element chemistry, bulk mineralogy, and clay mineralogy. An epidemiological study (N = 2367) and ethnographic interviews (N = 57) on Pemba yielded information about geophagic behaviors and socio-demographic and biological characteristics of those who consumed earth. The soils varied widely in color, ranging from light red to white through various shades of brown and yellow, and texture ranged from clay to sand. Major element chemistry of the soils also varied greatly; most were low in Fe and Ca. Trace elements, whether of biological or non-biological significance, were uniformly low when compared with normal ranges of mineral soils. The sole commonality among the samples is that all clay fractions were dominated by a kaolin mineral: kaolinite, halloysite, or a mixture of both. Geophagy behavior also varied greatly, with one major exception: a greater proportion of pregnant women (7.1%) and young children (4.5%) consumed earth than non-pregnant women (0.2%) or men (0%). The presence of kaolin mineral in all samples, its palliative and detoxifying properties, and the highest prevalence of geophagy among those most biologically vulnerable suggest that geophagy may be a protective behavior.