Subduction zone magmas are more oxidised on eruption than those at mid-ocean ridges. This is attributed either to oxidising components, derived from subducted lithosphere (slab) and added to the ...mantle wedge, or to oxidation processes occurring during magma ascent via differentiation. Here we provide direct evidence for contributions of oxidising slab agents to melts trapped in the sub-arc mantle. Measurements of sulfur (S) valence state in sub-arc mantle peridotites identify sulfate, both as crystalline anhydrite (CaSO
) and dissolved SO
in spinel-hosted glass (formerly melt) inclusions. Copper-rich sulfide precipitates in the inclusions and increased Fe
/∑Fe in spinel record a S
-Fe
redox coupling during melt percolation through the sub-arc mantle. Sulfate-rich glass inclusions exhibit high U/Th, Pb/Ce, Sr/Nd and δ
S (+ 7 to + 11‰), indicating the involvement of dehydration products of serpentinised slab rocks in their parental melt sources. These observations provide a link between liberated slab components and oxidised arc magmas.
In this trial involving women undergoing cesarean delivery (all of whom received prophylactic uterotonic medication), tranexamic acid treatment resulted in a significantly lower incidence of ...estimated blood loss greater than 1000 ml or red-cell transfusion by day 2 than placebo, but it did not reduce the risk of hemorrhage-related secondary clinical outcomes.
We report petrographic, major and trace element data for xenoliths from the andesitic Avacha volcano (Kamchatka), which host orthopyroxene (opx)-rich veins of mantle origin formed either by rapid ...crystallization of intruded melts or by their interaction with the host harzburgite. Studies of such veins may give better insights into sub-arc mantle processes (in particular on a millimetre to centimetre scale) than those of (1) arc xenoliths that do not preserve solidified initial metasomatizing agents, (2) massif peridotites, probably modified during their emplacement, or (3) arc magmatic rocks, which provide indirect information. We seek to trace the evolution of these agents as they react with the host peridotite and to assess their impact on the wall-rocks. The veins cross-cut spinel harzburgite and consist mainly of opx with minor olivine, clinopyroxene (cpx) and/or amphibole. We identify 'rapidly crystallized' veins that cut wall-rock olivine without petrographic evidence of reaction, and 'reactive' veins subdivided into 'thick' (0*5-1 mm) and 'thin' (<€0*5 mm). Minerals in the rapidly crystallized veins are depleted in rare earth elements (REE) and high field strength elements (HFSE) and enriched in fluid-mobile elements relative to REE. Minerals in the reactive veins have higher Ti, Al, Cr and alkalis than minerals in the rapidly crystallized veins, as well as highly variable trace element abundances, especially in reaction zones, thin veins and related metasomatic pockets in the host peridotite. They commonly show U-shaped REE patterns and positive Zr and Hf spikes in normalized trace element patterns. Our data, supported by recent reports, show that the rapidly crystallized veins formed between 1200°C and 900°C from a liquid derived by fluid-fluxed melting of a refractory (harzburgitic) mantle source depleted in heavy REE. The reactive veins formed via 'fractionation-reactive percolation' from fractionated hydrous derivatives of the melts that precipitated the rapidly crystallized veins. These liquids re-equilibrated with the host through diffusion and fluid-assisted dissolution-precipitation reactions, whose end-products are thin reactive veins and metasomatic pockets with distinctive U-shaped REE patterns and Zr-Hf spikes. Some Avacha xenoliths contain veins of Fe-rich amphibole deposited from the host magma that penetrated fractures in the peridotite fragments during their transport to the surface. These products of contamination were mistakenly attributed to mantle metasomatism in previous studies of other suites of Avacha mantle xenoliths. Trace element abundances in such veins are higher than for reactive veins of mantle origin, but both have similar trace element patterns (U-shaped REE patterns and Zr-Hf spikes) suggesting that 'fractionation-reactive percolation' also took place during their formation and is common during interaction of refractory peridotites with percolating melts and fluids. Metasomatic pockets of cpx and amphibole replacing coarse opx and spinel in the host peridotites commonly occur in the vicinity of fractures that lead to reactive opx-rich veins. The cpx and amphiboles in the pockets show progressive depletion in middle REE and HFSE at constant light REE and/or large ion lithophile elements away from the veins towards the host. This indicates that residual hydrous fluids expelled from the source veins enriched the wall-rock peridotites in incompatible elements but were progressively modified by reaction with the host with increasing percolation distance. This process produces disseminated pockets of metasomatic minerals with a broad range of compositions from a single initial liquid and strongly affects the trace element budgets of the harzburgite xenoliths from Avacha. We show that melts and fluids are likely to undergo profound transformation as they travel through and react with the refractory host mantle, even on a millimetre to centimetre scale. The composition of the initial metasomatizing agents can only be inferred from the composition of the metasomatic phases in mantle rocks combined with appropriate partition coefficients if these phases come from well-equilibrated mineral assemblages located close to melt and/or fluid sources.
•First stable iron isotope data from Pitcairn island, the type-locality of EM1 ocean island basalts.•Stable iron isotopes in primitive plume-related melts show a strong covariation with radiogenic ...Sr, Nd, Pb isotopes.•Mixing of primitive and enriched plume components occurs during melting at mantle depth.•Radiogenic isotope trajectories in OIB are mixing arrays between enriched components and plume matrix.
Ocean-island basalts (OIB) are the products of intra-plate mantle melting above mantle plumes. These hot, buoyant upwellings rise from the deep mantle, possibly the core-mantle boundary, to the Earth's surface. Radiogenic isotope signatures of trace elements in OIB are consistent with a variety of crustally-derived recycled components in their source that are suggested to reside in the plume as eclogite or their pyroxenitic melt-reaction products. The global OIB compositional spectrum exhibits a continuum of radiogenic isotope characteristics (Sr-Nd-Pb-Hf) that indicate mixing of these plume components. However, the petrological mechanisms underpinning this mixing remain elusive. Here, we report stable Fe isotope data for plume-derived lavas of Pitcairn Island from the southwest Pacific. Iron isotope compositions, corrected for olivine fractionation, show a strong co-variation with radiogenic Nd-Sr-Pb isotopes. At Pitcairn, two isotopically distinct components have been identified, one being an enriched-mantle 1 (EM-1) component and the other being a more primitive component, which plots in multiple radiogenic isotope space in the so-called focal zone (FOZO), tentatively identified here as the plume matrix. We suggest a two-stage scenario in which Fe isotopes are first fractionated towards heavier values during formation of a reaction-zone pyroxenite. Partial silicate melt derived from a recycled crustal eclogite, assumed here to be of a subducted sediment origin, reacts with ambient peridotite to form an isotopically heavier Fe isotope pyroxenite with memory of its precursor in radiogenic isotopes. Subsequently, both, isolated and enriched reaction zone pyroxenites and ambient plume matrix reach their solidus and mixing of their partial melts to variable proportions create the spread in radiogenic and stable isotope systematics. This mixing of components is coherent with the widely observed disparity in trajectories between plume matrix and enriched components in long-lived (Sr-Nd-Pb-Hf) and extinct (W) radiogenic and stable (Fe-Mg) isotope systematics and marks a fundamental process for chemical diversity in OIB. It supports a model of isolated plume components in a primitive mantle matrix. Enriched components in the plume that contribute to this mixing appear to be solely pyroxenitic with no or very little direct contribution from the original eclogite. Timing and loci of pyroxenite formation remain to be elucidated.
Considering the wide range of therapeutic options for localized prostate cancer (e.g., active surveillance, radiation-beam therapy, focal therapy, and radical prostatectomy), accurate assessment of ...the aggressiveness and localization of primary prostate cancer lesions is essential for treatment decision making. National Comprehensive Cancer Network guidelines recognize prostate-specific membrane antigen (PSMA) PET/CT for use in initial staging of high-risk primary prostate cancer. The gastrin-releasing peptide receptor (GRP-R) is a neuropeptide receptor overexpressed by low-risk prostate cancer cells. We aimed to perform the first (to our knowledge) prospective head-to-head comparison of PSMA- and GRP-R–targeted imaging at initial staging to understand how PSMA PET and GRP-R PET can be used or combined in clinical practice. Methods: This was a prospective, single-center, diagnostic cross-sectional imaging study using anonymized, masked, and independent interpretations of paired PET/CT studies in 22 patients with 68Ga-PSMA-617 (a radiolabeled PSMA inhibitor) and 68Ga-RM2 (68Ga-DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2, a radiolabeled GRP-R antagonist). We enrolled patients with newly diagnosed, biopsy-proven prostate cancer. None had received neoadjuvant hormone therapy or chemotherapy, and all underwent extended pelvic lymph node dissection. Histologic findings served as a reference. Results: On a lesion-based analysis (including lesions < 0.1 cm3), 68Ga-PSMA-617 PET/CT detected 74.3% (26/35) of all tumor lesions and 68Ga-RM2 PET/CT detected 78.1% (25/32; 1 patient could not be offered 68Ga-RM2 PET/CT). Paired examinations showed positive uptake of the 2 tracers in 21 of 32 lesions (65.6%), negative uptake in 5 of 32 lesions (15.6%), and discordant uptake in 6 of 32 lesions (18.8%). Uptake of 68Ga-PSMA-617 was higher when the International Society of Urological Pathology (ISUP) score was at least 4 versus at least 1 (P < 0.0001) or 2 (P = 0.0002). There were no significant differences in uptake between ISUP scores for 68Ga-RM2. Median 68Ga-RM2 SUVmax was significantly higher than median 68Ga-PSMA-617 SUVmax in the ISUP-2 subgroup (P = 0.01). Conclusion: 68Ga-PSMA-617 PET/CT is useful to depict higher, more clinically significant ISUP score lesions, and 68Ga-RM2 PET/CT has a higher detection rate for low-ISUP tumors. Combining PSMA PET and GRP-R PET allows for better classification of intraprostatic lesions.
A monocentric open-label randomized controlled trial (MRCT).
Comparison of clinical and radiological outcomes between isolated instrumented posterior fusion (PLF) and associated instrumented ...posterior fusion and interbody fusion by transforaminal approach (PLF + TLIF) for patients suffering from one-level lumbar degenerative spondylolisthesis (DS) undergoing surgery.
DS is a common cause of symptomatic lumbar stenosis. PLF has shown better clinical outcome than decompression with noninstrumented posterolateral fusion. TLIF with interbody cage showed better fusion rate than PLF. There is a need for randomized controlled trials to compare PLF with and without TLIF as to clinical and radiological outcomes.
This is a MRCT comparing PLF and TLIF techniques in surgical treatment of DS. Sixty patients were included in a secured database from 2009 to 2011 and randomized into two groups: 30 PLF with posterior pedicle screws and intertransverse autologuous graft, and 30 TLIF in which an interbody fusion by transforaminal approach was added. Data included clinical (pain and disability), surgical (blood loss and operating time), and radiological (alignment and fusion) parameters at baseline and 2-year follow-up. Comparison was made by Student t test and Chi-square test.
There was a significant improvement in each group for pain and disability but no difference between the groups. Radiographic assessment showed better posterolateral fusion rate for TLIF without superiority in segmental lordosis improvement. A case of deformity cascade with spino-pelvic mismatch at baseline was noted in PLF.
Posterior decompression and instrumented fusion is an efficient technique that proved its significant clinical benefit in the surgical treatment of DS. TLIF did not show its superiority neither in clinical nor alignment parameters despite a better fusion rate. These results suggest that TLIF is not mandatory in this specific indication. Sagittal alignment analysis by standing full-body images should be considered in DS care.
2.
Soft-tissue sarcomas (STS) represent a heterogeneous group of rare tumors including more than 70 different histological subtypes. High throughput molecular analysis (next generation sequencing exome ...NGS) is a unique opportunity to identify driver mutations that can change the usual one-size-fits-all treatment paradigm to a patient-driven therapeutic strategy. The primary objective of the MULTISARC trial is to assess whether NGS can be conducted for a large proportion of metastatic STS participants within a reasonable time, and, secondarily to determine whether a NGS-guided therapeutic strategy improves participant's outcome.
This is a randomized, multicentre, phase II/III trial inspired by the design of umbrella and biomarker-driven trials. The setting plans up to 17 investigational centres across France and the recruitment of 960 participants. Participants aged at least 18 years, with unresectable locally advanced and/or metastatic STS confirmed by the French sarcoma pathological reference network, are randomized according to 1:1 allocation ratio between the experimental arm "NGS" and the standard "No NGS". NGS will be considered feasible if (i) NGS results are available and interpretable, and (ii) a report of exome sequencing including a clinical recommendation from a multidisciplinary tumor board is provided to investigators within 7 weeks from reception of the samples on the biopathological platform. A feasibility rate of more than 70% is expected (null hypothesis: 70% versus alternative hypothesis: 80%). In terms of care, participants randomized in "No NGS" arm and who fail treatment will be able to switch to the NGS arm at the request of the investigator.
The MULTISARC trial is a prospective study designed to provide high-level evidence to support the implementation of NGS in routine clinical practice for advanced STS participants, on a large scale.
clinicaltrial.gov NCT03784014 .
Value of information is now recognized as a reference method in the decision process underpinning cost-effectiveness evaluation. The expected value of perfect information (EVPI) is the expected value ...from completely reducing the uncertainty surrounding the cost-effectiveness of an innovative intervention. Among sample size calculation methods used in cost-effectiveness studies, only one is coherent with this decision framework. It uses a Bayesian approach and requires data of a pre-existing cost-effectiveness study to derive a valid prior EVPI. When evaluating the cost-effectiveness of innovations, no observed prior EVPI is usually available to calculate the sample size. We here propose a sample size calculation method for cost-effectiveness studies, that follows the value of information theory, and, being frequentist, can be based on assumptions if no observed prior EVPI is available.
The general principle of our method is to define the sampling distribution of the incremental net monetary benefit (ΔB), or the distribution of ΔB that would be observed in a planned cost-effectiveness study of size n. Based on this sampling distribution, the EVPI that would remain at the end of the trial (EVPI
) is estimated. The optimal sample size of the planned cost-effectiveness study is the n for which the cost of including an additional participant becomes equal or higher than the value of the information gathered through this inclusion.
Our method is illustrated through four examples. The first one is used to present the method in depth and describe how the sample size may vary according to the parameters' value. The three other examples are used to illustrate in different situations how the sample size may vary according to the ceiling cost-effectiveness ratio, and how it compares with a test statistic-based method. We developed an R package (EBASS) to run these calculations.
Our sample size calculation method follows the value of information theory that is now recommended for analyzing and interpreting cost-effectiveness data, and sets the size of a study that balances its cost and the value of its information.
Objective
To evaluate if positioning the upper-limb promoting abduction, external rotation and flexion of the shoulder reduces the intensity of post-stroke shoulder pain at day-7 compared to usual ...clinical practice.
Design & setting
Prospective single-center randomized clinical trial using a superiority design comparing two preventive strategies of post-stroke shoulder pain in a stroke unit.
Subjects
Patients were included within 2 days from a first symptomatic ischemic stroke affecting shoulder motor function.
Interventions
Intervention group included specific positioning of the shoulder in abduction, external rotation and flexion in bed, chair and during mobilization. Control group referred to usual practice i.e. positioning using a standard support scarf.
Main measures
Primary outcome was the intensity of shoulder pain assessed by the visual analog scale (VAS) (0–100) at day-7 post-stroke. Other outcomes measured at day-7 and 2 months post-stroke were the VAS, motor function, spasticity, depression, functional independence and rates of complex regional Pain syndrome (CRPS).
Results
76 patients (49 males; mean age = 68.3) were randomized. The shoulder pain at day-7 was not different between the control group (16.1, SD = 27.4) and the intervention group (10.3, SD = 21.5, p = 0.18) as well as at 2 months (p = 0.12). A lower rate of depression was observed in the intervention group at 2 months 36.7% (CI95% 19.9;56.1) vs 52.9% (CI95% 35.1;70.2). No between-group difference in other outcomes was observed at 2 months.
Conclusions
This study failed to demonstrate the benefit of a specific positioning tool in reducing the intensity of post-stroke shoulder pain which was lower than previously reported in the literature.
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