The lithospheric-to-lower-mantle carbon cycle recorded in superdeep diamonds.

The transport of carbon into Earth's mantle is a critical pathway in Earth's carbon cycle, affecting both the climate and the redox conditions of the surface and mantle. The largest unconstrained variables in this cycle are the depths to which carbon in sediments and altered oceanic crust can be subducted and the relative contributions of these reservoirs to the sequestration of carbon in the deep mantle1. Mineral inclusions in sublithospheric, or 'superdeep', diamonds (derived from depths greater than 250 kilometres) can be used to constrain these variables. Here we present oxygen isotope measurements of mineral inclusions within diamonds from Kankan, Guinea that are derived from depths extending from the lithosphere to the lower mantle (greater than 660 kilometres). These data, combined with the carbon and nitrogen isotope contents of the diamonds, indicate that carbonated igneous oceanic crust, not sediment, is the primary carbon-bearing reservoir in slabs subducted to deep-lithospheric and transition-zone depths (less than 660 kilometres). Within this depth regime, sublithospheric inclusions are distinctly enriched in 18O relative to eclogitic lithospheric inclusions derived from crustal protoliths. The increased 18O content of these sublithospheric inclusions results from their crystallization from melts of carbonate-rich subducted oceanic crust. In contrast, lower-mantle mineral inclusions and their host diamonds (deeper than 660 kilometres) have a narrow range of isotopic values that are typical of mantle that has experienced little or no crustal interaction. Because carbon is hosted in metals, rather than in diamond, in the reduced, volatile-poor lower mantle2, carbon must be mobilized and concentrated to form lower-mantle diamonds. Our data support a model in which the hydration of the uppermost lower mantle by subducted oceanic lithosphere destabilizes carbon-bearing metals to form diamond, without disturbing the ambient-mantle stable-isotope signatures. This transition from carbonate slab melting in the transition zone to slab dehydration in the lower mantle supports a lower-mantle barrier for carbon subduction.

Primordial and recycled helium isotope signatures in the mantle transition zone.

Isotope compositions of basalts provide information about the chemical reservoirs in Earth's interior and play a critical role in defining models of Earth's structure. However, the helium isotope signature of the mantle below depths of a few hundred kilometers has been difficult to measure directly. This information is a vital baseline for understanding helium isotopes in erupted basalts. We measured He-Sr-Pb isotope ratios in superdeep diamond fluid inclusions from the transition zone (depth of 410 to 660 kilometers) unaffected by degassing and shallow crustal contamination. We found extreme He-C-Pb-Sr isotope variability, with high 3He/4He ratios related to higher helium concentrations. This indicates that a less degassed, high-3He/4He deep mantle source infiltrates the transition zone, where it interacts with recycled material, creating the diverse compositions recorded in ocean island basalts.

CaSiO3 perovskite in diamond indicates the recycling of oceanic crust into the lower mantle.

Laboratory experiments and seismology data have created a clear theoretical picture of the most abundant minerals that comprise the deeper parts of the Earth's mantle. Discoveries of some of these minerals in 'super-deep' diamonds-formed between two hundred and about one thousand kilometres into the lower mantle-have confirmed part of this picture. A notable exception is the high-pressure perovskite-structured polymorph of calcium silicate (CaSiO3). This mineral-expected to be the fourth most abundant in the Earth-has not previously been found in nature. Being the dominant host for calcium and, owing to its accommodating crystal structure, the major sink for heat-producing elements (potassium, uranium and thorium) in the transition zone and lower mantle, it is critical to establish its presence. Here we report the discovery of the perovskite-structured polymorph of CaSiO3 in a diamond from South African Cullinan kimberlite. The mineral is intergrown with about six per cent calcium titanate (CaTiO3). The titanium-rich composition of this inclusion indicates a bulk composition consistent with derivation from basaltic oceanic crust subducted to pressures equivalent to those present at the depths of the uppermost lower mantle. The relatively 'heavy' carbon isotopic composition of the surrounding diamond, together with the pristine high-pressure CaSiO3 structure, provides evidence for the recycling of oceanic crust and surficial carbon to lower-mantle depths.

Contextual representations of negative images modulate intrusion frequency in an intrusion provocation paradigm.

BACKGROUND AND OBJECTIVES: To understand how memories of negative events become highly accessible in the context of trauma, we tested the hypothesis that contextual information modulates how easily intrusions can be provoked by perceptual stimuli.. METHODS: Healthy participants viewed pictures depicting trauma scenes either with or without accompanying moderate (i.e. survival, recovery) or severe (i.e. fatality, permanent injury) outcome information. All participants viewed the same depictions of trauma scenes. Involuntary memories for the pictures were assessed using self-report diaries and an adapted version of the Impact of Event Scales (IES). A blurred picture perceptual priming paradigm was adapted to be used as an intrusion provocation task. RESULTS: The severe outcome group experienced a significantly higher frequency of intrusions on the intrusion provocation task in comparison to both moderate outcome and control (no-context) conditions. The severe outcome condition did not increase intrusions on the self-report diaries or the adapted IES. There was no effect of condition on ratings for the emotionality, self-relevance, valence, or seriousness of the trauma scenes. LIMITATIONS: The analogue method should not be generalized directly to incidences of real-life trauma. It was unclear why differences in intrusion frequency were found in the provocation task only. The relative amount of individual conceptual and data-driven processing adopted by the participants was not assessed. CONCLUSIONS: Manipulating contextual information that determines the meaning of sensory-perceptual features for a trauma scene can modulate subsequent intrusion frequency in response to visually similar cues.

Hydrous mantle transition zone indicated by ringwoodite included within diamond.

The ultimate origin of water in the Earth's hydrosphere is in the deep Earth--the mantle. Theory and experiments have shown that although the water storage capacity of olivine-dominated shallow mantle is limited, the Earth's transition zone, at depths between 410 and 660 kilometres, could be a major repository for water, owing to the ability of the higher-pressure polymorphs of olivine--wadsleyite and ringwoodite--to host enough water to comprise up to around 2.5 per cent of their weight. A hydrous transition zone may have a key role in terrestrial magmatism and plate tectonics, yet despite experimental demonstration of the water-bearing capacity of these phases, geophysical probes such as electrical conductivity have provided conflicting results, and the issue of whether the transition zone contains abundant water remains highly controversial. Here we report X-ray diffraction, Raman and infrared spectroscopic data that provide, to our knowledge, the first evidence for the terrestrial occurrence of any higher-pressure polymorph of olivine: we find ringwoodite included in a diamond from Juína, Brazil. The water-rich nature of this inclusion, indicated by infrared absorption, along with the preservation of the ringwoodite, is direct evidence that, at least locally, the transition zone is hydrous, to about 1 weight per cent. The finding also indicates that some kimberlites must have their primary sources in this deep mantle region.

Isotopic tracing of the impact of mobility on infectious disease: The origin of people with treponematosis buried in hull, England, in the late medieval period.

Treponematosis has been one of the most studied and debated infectious diseases in paleopathology, particularly from the standpoint of its origin, evolution, and transmission. This study links evidence for treponematosis in skeletons from the 14th-16th century AD cemetery of the Augustinian friary of Hull Magistrates Court, England, with data from stable isotope analysis to test the hypothesis that the people with treponemal disease buried at this site were not locally born and raised. The objective is to explore the potential of using stable isotope data to track the place of origin and extent of mobility of individuals with an infectious disease. Dental enamel samples of 12 skeletons were selected for strontium ((87) Sr/(86) Sr ratio) and oxygen (δ(18) O) stable isotope analysis based on the presence (six - diseased) or absence (six - controls) of bone changes associated with treponemal disease. The oxygen isotope ratios of all but three individuals (1047, 1121, 823) overlapped at two standard deviations with the inferred local precipitation range, and only one individual (1216) had a strontium isotope ratio outside the regional range. Two of the four had probable/possible treponemal bone changes. Those with treponemal bone changes were not demonstrably more likely to be migrants than those without such lesions. However, because of extensive documentary evidence for trade with the Baltic Sea area, and for merchants from towns such as Stralsund, Danzig and Elbing being in Hull, it is very plausible that the four migrants came from the Baltic area or even southern Sweden.

A Phase I clinical study of cisplatin-incorporated polymeric micelles (NC-6004) in patients with solid tumours.

BACKGROUND: On the basis of preclinical studies of NC-6004, a cisplatin-incorporated micellar formulation, we hypothesised that NC-6004 could show lower toxicity than cisplatin and show greater anti-tumour activity in phase I study. METHODS: A total of 17 patients were recruited in a range of advanced solid tumour types. NC-6004 was administered intravenously (i.v.) every 3 weeks. The dose escalation started at 10 mg m(-2) and was increased up to 120 mg m(-2) according to the accelerated titration method and modified Fibonacci method. RESULTS: One dose-limiting toxicity (DLT) occurred in a patient who was given 90 mg m(-2) of NC-6004, otherwise any significant cisplatin-related toxicity was not observed or generally mild toxicity was observed. Despite the implementation of post-hydration and pre-medication regimen, renal impairment and hypersensitivity reactions still developed at 120 mg m(-2), which led to the conclusion that the maximum tolerated dose was 120 mg m(-2), and the recommended dose was 90 mg m(-2), although DLT was not defined as per protocol. Stable disease was observed in seven patients. The maximum concentration and area under the concentration-time curve of ultrafilterable platinum at 120 mg m(-2) NC-6004 were 34-fold smaller and 8.5-fold larger, respectively, than those for cisplatin. CONCLUSION: The delayed and sustained release of cisplatin after i.v. administration contributes to the low toxicity of NC-6004.

Contribution of HIF-1 and drug penetrance to oxaliplatin resistance in hypoxic colorectal cancer cells.

BACKGROUND: Hypoxia is as an indicator of poor treatment outcome. Consistently, hypoxic HCT116 colorectal cancer cells are resistant to oxaliplatin, although the mechanistic basis is unclear. This study sought to investigate the relative contribution of HIF-1 (hypoxia-inducible factor-1)-mediated gene expression and drug penetrance to oxaliplatin resistance using three-dimensional spheroids. METHODS: Hypoxia-inducible factor-1alpha function was suppressed by the stable expression of a dominant-negative form in HCT116 cells (DN). Cells were drug exposed as monolayer or multicellular spheroid cultures. Cells residing at differing oxygenation status were isolated from Hoechst 33342-treated spheroids using flow cytometry. Sub-populations were subjected to clonogenic survival assays and to Inductively-Coupled Plasma Mass Spectroscopy to determine oxaliplatin uptake. RESULTS: In spheroids, a sensitivity gradient (hypoxic

Quantitative analysis of trace element concentrations in some gem-quality diamonds.

The geochemical signature of diamond-forming fluids can be used to unravel diamond-forming processes and is of potential use in the detection of so-called 'conflict' diamonds. While fluid-rich fibrous diamonds can be analyzed by a variety of techniques, very few data have been published for fluid-poor, gem-quality diamonds because of their very low impurity levels. Here we present a new ICPMS-based (ICPMS: inductively coupled plasma mass spectrometry) method for the analysis of trace element concentrations within fluid-poor, gem-quality diamonds. The method employs a closed-system laser ablation cell. Diamonds are ablated and the products trapped for later pre-concentration into solutions that are analyzed by sector-field ICPMS. We show that our limits of quantification for a wide range of elements are at the sub-pg to low pg level. The method is applied to a suite of 10 diamonds from the Cullinan Mine (previously known as Premier), South Africa, along with other diamonds from Siberia (Mir and Udachnaya) and Venezuela. The concentrations of a wide range of elements for all the samples (expressed by weight in the solid) are very low, with rare earth elements along with Y, Nb, Cs ranging from 0.01 to 2 ppb. Large ion lithophile elements (LILE) such as Rb and Ba vary from 1 to 30 ppb. Ti ranges from ppb levels up to 2 ppm. From the combined, currently small data set we observe two kinds of diamond-forming fluids within gem diamonds. One group has enrichments in LILE over Nb, whereas a second group has normalized LILE abundances more similar to those of Nb. These two groups bear some similarity to different groups of fluid-rich diamonds, providing some supporting evidence of a link between the parental fluids for both fluid-inclusion-rich and gem diamonds.

A link between large mantle melting events and continent growth seen in osmium isotopes.

Although Earth's continental crust is thought to have been derived from the mantle, the timing and mode of crust formation have proven to be elusive issues. The area of preserved crust diminishes markedly with age, and this can be interpreted as being the result of either the progressive accumulation of new crust or the tectonic recycling of old crust. However, there is a disproportionate amount of crust of certain ages, with the main peaks being 1.2, 1.9, 2.7 and 3.3 billion years old; this has led to a third model in which the crust has grown through time in pulses, although peaks in continental crust ages could also record preferential preservation. The 187Re-187Os decay system is unique in its ability to track melt depletion events within the mantle and could therefore potentially link the crust and mantle differentiation records. Here we employ a laser ablation technique to analyse large numbers of osmium alloy grains to quantify the distribution of depletion ages in the Earth's upper mantle. Statistical analysis of these data, combined with other samples of the upper mantle, show that depletion ages are not evenly distributed but cluster in distinct periods, around 1.2, 1.9 and 2.7 billion years. These mantle depletion events coincide with peaks in the generation of continental crust and so provide evidence of coupled, global and pulsed mantle-crust differentiation, lending strong support to pulsed models of continental growth by means of large-scale mantle melting events.

Adaptive dosing and platinum-DNA adduct formation in children receiving high-dose carboplatin for the treatment of solid tumours.

A pharmacokinetic-pharmacodynamic study was carried out to investigate the feasibility and potential importance of therapeutic monitoring following high-dose carboplatin treatment in children. High-dose carboplatin was administered over 3 or 5 days, with the initial dose based on renal function, to achieve target area under the plasma concentration-time curve (AUC) values of 21 or 20 mg ml(-1).min, respectively. Dose adjustment was carried out based on observed individual daily AUC values, to obtain the defined target exposures. Platinum-DNA adduct levels were determined in peripheral blood leucocytes and toxicity data were obtained. Twenty-eight children were studied. Based on observed AUC values, carboplatin dose adjustment was performed in 75% (21 out of 28) patients. Therapeutic monitoring resulted in the achievement of carboplatin exposures within 80-126% of target AUC values, as compared to estimated exposures of 65-213% of target values without dose adjustment. The carboplatin AUC predicted with no dose modification was positively correlated with pretreatment glomerular filtration rate (GFR) values. Higher GFR values were observed in those patients who would have experienced AUC values >25% above the target AUC than those patients attaining AUC values >25% below the target AUC, following renal function-based dosing. Platinum-DNA adduct levels correlated with observed AUC values on day 1 of carboplatin and increased over a 5-day course of treatment. Real-time monitoring of carboplatin pharmacokinetics with adaptive dosing is both feasible and necessary for the attainment of consistent AUC values in children receiving high-dose carboplatin treatment. Pharmacodynamic data suggest a strong correlation between carboplatin pharmacokinetics and the drug-target interaction.

The continental lithospheric mantle: characteristics and significance as a mantle reservoir.

The continental lithospheric mantle (CLM) is a small-volumed (ca. 2.5% of the total mantle), chemically distinct mantle reservoir that has been suggested to play a role in the source of continental and oceanic magmatism. It is our most easily identifiable reservoir for preserving chemical heterogeneity in the mantle. Petrological and geophysical constraints indicate that the maximum depth of the CLM is ca. 250 km. There is a clear secular variation of CLM composition, such that CLM formed in the last 2 Gyr is less depleted and therefore less dynamically stable than ancient CLM formed in the Archean. We present new trace-element data for kimberlite-hosted lithospheric peridotites and metasomites. These data, combined with other data for spinel peridotites from non-cratonic regions, show that neither hydrous nor anhydrous lithospheric mantle xenoliths make suitable sources for continental or oceanic basalts. Addition of a hydrous phase, either amphibole or phlogopite, to depleted peridotite results in positive Nb and Ti anomalies that are the opposite of those predicted for some flood-basalt sources on the basis of their trace-element abundances. Overall, the Sr and Nd isotopic composition of cratonic and non-cratonic CLM is close to bulk Earth, with cratonic CLM showing small numbers of extreme compositions. Thus, while the CLM is certainly ancient in many locations, its average composition is not significantly 'enriched' over primitive upper mantle, in terms of either radiogenic isotopes or trace elements. These characteristics, plus a change in lithospheric chemistry with depth, indicate that the elemental and isotopic composition of lithospheric mantle likely to be re-incorporated into convecting mantle via delamination/thermal erosion processes is probably not very distinct from that of the convecting mantle. These observations lead us to question the requirement for CLM participation in the source of oceanic magmas and to promote consideration of a mantle that is chemically heterogeneous on all scales. Hf and Nd isotope compositions identify a distinctive source component in deeply derived alkaline volcanics associated with continents. This component cannot be constrained to the CLM but may originate from a deeper reservoir of ancient, subducted oceanic crust stored in the mantle.