The role of diffusion-driven pure climb creep on the rheology of bridgmanite under lower mantle conditions

The viscosity of Earth’s lower mantle is poorly constrained due to the lack of knowledge on some fundamental variables that affect the deformation behaviour of its main mineral phases. This study focuses on bridgmanite, the main lower mantle constituent, and assesses its rheology by developing an approach based on mineral physics. Following and revising the recent advances in this field, pure climb creep controlled by diffusion is identified as the key mechanism driving deformation in bridgmanite. The strain rates of this phase under lower mantle pressures, temperatures and stresses are thus calculated by constraining diffusion and implementing a creep theoretical model. The viscosity of MgSiO_3 bridgmanite resulting from pure climb creep is consequently evaluated and compared with the viscosity profiles available from the literature. We show that the inferred variability of viscosity in these profiles can be fully accounted for with the chosen variables of our calculation, e.g., diffusion coefficients, vacancy concentrations and applied stresses. A refinement of these variables is advocated in order to further constrain viscosity and match the observables

ERG Deregulation Induces PIM1 Over-Expression and Aneuploidy in Prostate Epithelial Cells

The ERG gene belongs to the ETS family of transcription factors and has been found to be involved in atypical chromosomal rearrangements in several cancers. To gain insight into the oncogenic activity of ERG, we compared the gene expression profile of NIH-3T3 cells stably expressing the coding regions of the three main ERG oncogenic fusions: TMPRSS2/ERG (tERG), EWS/ERG and FUS/ERG. We found that all three ERG fusions significantly up-regulate PIM1 expression in the NIH-3T3 cell line. PIM1 is a serine/threonine kinase frequently over-expressed in cancers of haematological and epithelial origin. We show here that tERG expression induces PIM1 in the non-malignant prostate cell line RWPE-1, strengthening the relation between tERG and PIM1 up-regulation in the initial stages of prostate carcinogenesis. Silencing of tERG reversed PIM1 induction. A significant association between ERG and PIM1 expression in clinical prostate carcinoma specimens was found, suggesting that such a mechanism may be relevant in vivo. Chromatin Immunoprecipitation experiments showed that tERG directly binds to PIM1 promoter in the RWPE-1 prostate cell line, suggesting that tERG could be a direct regulator of PIM1 expression. The up-regulation of PIM1 induced by tERG over-expression significantly modified Cyclin B1 levels and increased the percentage of aneuploid cells in the RWPE-1 cell line after taxane-based treatment. Here we provide the first evidence for an ERG-mediated PIM1 up-regulation in prostate cells in vitro and in vivo, suggesting a direct effect of ERG transcriptional activity in the alteration of genetic stability

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice

IMPORTANCE: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. OBJECTIVE: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. EXPOSURES: Genetic test results. MAIN OUTCOMES AND MEASURES: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. RESULTS: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%). CONCLUSIONS AND RELEVANCE: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes

Fractional melting and smelting on the Ureilite parent body.

We investigate petrologic and physical aspects of melt extraction on the parent asteroid of the ureilite meteorites (UPB). We first develop a petrologic model for simultaneous melting and smelting (reduction of FeO by C) at various depths. For a model starting composition, determined from petrologic constraints to have been CV-like except for elevated Ca/Al (2.5 × CI), we determine (1) degree of melting, (2) the evolution of mg, (3) production of CO + CO2 gas and (4) the evolution of mineralogy in the residue as a function of temperature and pressure. We then use these relationships to examine implications of fractional vs. batch melt extraction. In the shallowest source regions (30 bars), melting and smelting begin simultaneously at 1050 °C, so that mg and the abundance of low-Ca pyroxene (initially pigeonite, ultimately pigeonite + orthopyroxene) begin to increase immediately. However, in the deepest source regions (100 bars), smelting does not begin until 1200 °C, so that mg begins to increase and low-Ca pyroxene (pigeonite) appears only after 21% melting. The final residues in these two cases, obtained just after the demise of augite, match the end-members of the ureilite mg range (94–76) in pyroxene abundance and type. In all source regions, production of CO + CO2 by smelting varies over the course of melting. The onset of smelting results in a burst of gas production and very high incremental gas/melt ratios (up to 2.5 by mass); after a few % (s)melting, however, these values drastically decline (to <0.05 in the final increments). Physical modelling based on these relationships indicates that melts would begin to migrate upwards after only 1–2% melting, and thereafter would migrate continuously (fractionally) and rapidly (reaching the surface in < a year) in a network of veins/dikes. All melts produced during the smelting stage in each source region have gas contents sufficient to cause them to erupt explosively and be lost. However, since in all but the shallowest source regions part of the melting sequence occurs without smelting, fractional melting implies that a significant fraction of UPB melts may have erupted more placidly to form a thin crust (3.3 km thick for a 100 km radius body). Our calculations suggest that melt extraction was so rapid that equilibrium trace element partitioning may not have been attained. We present a model for disequilibrium fractional melting (in which REE partitioning is limited by diffusion) on the UPB, and demonstrate that it produces a good match to the ureilite data. The disequilibrium model may also apply to trace siderophile elements, and might help explain the “overabundance” of these elements in ureilites relative to predictions from the smelting model. Our results suggest that melt extraction on the UPB was a rapid, fractional process, which can explain the preservation of a primitive oxygen isotopic signature on the UPB

Timescales of magmatic processes : from core to atmosphere

Quantifying the timescales of current geological processes is critical for constraining the physical mechanisms operating on the Earth today. Since the Earth’s origin 4.55 billion years ago magmatic processes have continued to shape the Earth, producing the major reservoirs that exist today (core, mantle, crust, oceans and atmosphere) and promoting their continued evolution. But key questions remain. When did the core form and how quickly? How are magmas produced in the mantle, and how rapidly do they travel towards the surface? How long do magmas reside in the crust, differentiating and interacting with the host rocks to yield the diverse set of igneous rocks we see today? How fast are volcanic gases such as carbon dioxide released into the atmosphere? This book addresses these and other questions by reviewing the latest advances in a wide range of Earth Science disciplines: from the measurement of short-lived radionuclides to the study of element diffusion in crystals and numerical modelling of magma behaviour. It will be invaluable reading for advanced undergraduate and graduate students, as well as igneous petrologists, mineralogists and geochemists involved in the study of igneous rocks and processes.Extinct radionuclides and the earliest differentiation of the Earth and moon / G. Caro and T. Kleine -- Diffusion constraints on rates of melt production in the mantle / James A. Van Orman and Alberto E. Saal -- Melt production in the mantle: constraints from U-series / Bernard Bourdon and Tim Elliott -- Formulations for simulating the multiscale physics of magma ascent / Craig O'Neill and Marc Spiegelman -- Melt transport from the mantle to the crust : uranium-series isotopes / Simon P. Turner and Bernard Bourdon -- Rates of magma ascent : constraints from mantle-derived xenoliths / Suzanne Y. O'Reilly and W.L. Griffin -- Time constraints from chemical equilibration in magmatic crystals / Fidel Costa and Daniel Morgan -- Magma cooling and differentiation : uranium-series isotopes / Anthony Dosseto and Simon P. Turner -- Defining geochemical signatures and timescales of melting processes in the crust : an experimental tale of melt segregation, migration and emplacement / Tracy Rushmer and Kurt Knesel -- Timescales associated with large silicic magma bodies / Olivier Bachmann -- Timescales of magma degassing / Kim Berlo, James E. Gardner and Jonathan D. Blundy.264 page(s

Diffusive relaxation of carbon and nitrogen isotope heterogeneity in diamond: a new thermochronometer

International audienceThe spatial distribution of carbon and nitrogen isotopes in diamonds provides information on mantle residence time. Diamonds with long residence at high temperature will gradually lose their initial zoning patterns due to diffusion. Using experimentally determined carbon self-diffusion coefficients and nitrogen diffusion coefficients derived from aggregation experiments, we have modeled the diffusive relaxation of zoning profiles with a spectrum of wavelengths. Carbon isotope heterogeneity will be preserved on wavelengths greater than ∼1 μm after 1 billion years’ residence at 1400 K, and on wavelengths greater than ∼200 μm after 1 million years’ residence at 2000 K. Nitrogen isotope zoning is relaxed much more slowly, with 0.1 μm zoning preserved over the age of the Earth at 1400 K and 1 μm zoning preserved after 1 million years at 2000 K. The large difference in diffusive relaxation times between carbon and nitrogen isotopes means that initially correlated carbon and nitrogen profiles will lose their correlation after sufficient diffusion of carbon has taken place. This could be used as a thermochronometer. Carbon isotope heterogeneity in diamonds associated with lower mantle mineral assemblages has significantly smaller amplitude than nitrogen isotope heterogeneity, consistent with diffusive relaxation at high temperatures in the lower mantle

Thermal evolution and physics of melt extraction on the Ureilite Parent Body.

We develop a physical model of the thermal history of the ureilite parent body (UPB) that numerically tracks the history of its heating, hydration, dehydration, partial melting and smelting as a function of its formation time and the initial values of its composition, formation temperature and water ice content. Petrologic and chemical data from the main group (non-polymict) ureilite meteorites, which sample the interior of the UPB between depths corresponding to pressures in the range 3–10 MPa, are used to constrain the model. We find that to achieve the 30% melting inferred for ureilites from all sampled depths, the UPB must have had a radius between 80 and 130 km and must have accreted about 0.55 Ma after CAI formation. Melting began in the body at 1 Ma after CAI, and the time at which 30% melting was reached varied with depth in the asteroid but was always between 4.5 and 5.8 Ma after CAI. The total rate at which melt was produced in the UPB varied from more than 100 m3 s−1 in the very early stages of melting at 1 Ma after CAI to 5 m3 s−1 between 2 and 3 Ma after CAI, decreasing to extremely small values as the end of melting was approached beyond 5 Ma. Although the initial period of high melt production occupied only a short time around 1 Ma after CAI, it corresponded to half (16%) of total silicate melting, and all strictly basaltic (i.e. plagioclase-saturated) melts must have been produced during this period. A very efficient melt transport network, consisting of a hierarchy of veins and larger pathways (dikes), developed quickly at the start of melting, ensuring rapid (timescales of months) transport of any single parcel of melt to shallow levels, thus ensuring that chemical interaction between melts and the rocks through which they subsequently passed was negligible. Volatile (mainly carbon monoxide) production due to smelting began at the start of silicate melting in the shallowest parts of the UPB and at later times at greater depths. Except at the very start and very end of melting, the volatile content of the melts produced was always high – generally between 15 and 35 mass % – and most of the melt produced was erupted at the surface of the UPB with speeds well in excess of the escape velocity and was lost into space. However, we show that 30% melting at the 3 MPa pressure level was only possible if 15% of the total melt produced in the asteroid was retained as a small number (5) of very extensive, sill-like intrusions centered at a depth of 7 km below the surface, near the base of the 8 km thick outer crust of the asteroid that was maintained at temperatures below the basalt solidus by conductive heat loss to the surface. The horizontal extents of these sills occupied about 75% of the surface area of the UPB, and the sills acted as buffers between the steady supply of melt from depth and the intermittent explosive eruption of the melt into space. We infer that samples from these intrusions are preserved as the rare feldspathic (loosely basaltic) clasts in polymict ureilites, and show that the cooling histories of the sills are consistent with these clasts reaching isotopic closure at 5 Ma after CAI, as given by 26Al–26Mg, 53Mn–53Cr and Pb–Pb age dates