Experimental determination of magnesia and silica solubilities in graphite-saturated and redox-buffered high-pressure COH fluids in equilibrium with forsterite + enstatite and magnesite + enstatite

We experimentally investigated the dissolution of forsterite, enstatite and magnesite in graphite-saturated COH fluids, synthesized using a rocking piston cylinder apparatus at pressures from 1.0 to 2.1 GPa and temperatures from 700 to 1200 \ub0C. Synthetic forsterite, enstatite, and nearly pure natural magnesite were used as starting materials. Redox conditions were buffered by Ni\u2013NiO\u2013H2O (\u394FMQ = 12\u20090.21 to 12\u20091.01), employing a double-capsule setting. Fluids, binary H2O\u2013CO2 mixtures at the P, T, and fO2 conditions investigated, were generated from graphite, oxalic acid anhydrous (H2C2O4) and water. Their dissolved solute loads were analyzed through an improved version of the cryogenic technique, which takes into account the complexities associated with the presence of CO2-bearing fluids. The experimental data show that forsterite\u2009+\u2009enstatite solubility in H2O\u2013CO2 fluids is higher compared to pure water, both in terms of dissolved silica (mSiO2\u2009=\u20091.24 mol/kgH2O versus mSiO2\u2009=\u20090.22 mol/kgH2O at P\u2009=\u20091 GPa, T\u2009=\u2009800 \ub0C) and magnesia (mMgO\u2009=\u20091.08 mol/kgH2O versus mMgO\u2009=\u20090.28 mol/kgH2O) probably due to the formation of organic C\u2013Mg\u2013Si complexes. Our experimental results show that at low temperature conditions, a graphite-saturated H2O\u2013CO2 fluid interacting with a simplified model mantle composition, characterized by low MgO/SiO2 ratios, would lead to the formation of significant amounts of enstatite if solute concentrations are equal, while at higher temperatures these fluid, characterized by MgO/SiO2 ratios comparable with that of olivine, would be less effective in metasomatizing the surrounding rocks. However, the molality of COH fluids increases with pressure and temperature, and quintuplicates with respect to the carbon-free aqueous fluids. Therefore, the amount of fluid required to metasomatize the mantle decreases in the presence of carbon at high P\u2013T conditions. COH fluids are thus effective carriers of C, Mg and Si in the mantle wedge up to the shallowest level of the upper mantle

Dissolution susceptibility of glass-like carbon versus crystalline graphite in high-pressure aqueous fluids and implications for the behavior of organic matter in subduction zones

Organic matter, showing variable degrees of crystallinity and thus of graphitization, is an important source of carbon in subducted sediments, as demonstrated by the isotopic signatures of deep and ultra-deep diamonds and volcanic emissions in arc settings. In this experimental study, we investigated the dissolution of sp2 hybridized carbon in aqueous fluids at 1 and 3 GPa, and 800\ub0C, taking as end-members i) crystalline synthetic graphite and ii) X-ray amorphous glass-like carbon. We chose glass-like carbon as an analogue of natural \u201cdisordered\u201d graphitic carbon derived from organic matter, because unlike other forms of poorly ordered carbon it does not undergo any structural modification at the investigated experimental conditions, allowing approach to thermodynamic equilibrium. Textural observations, Raman spectroscopy, synchrotron X-ray diffraction and dissolution susceptibility of char produced by thermal decomposition of glucose (representative of non-transformed organic matter) at the same experimental conditions support this assumption. The redox state of the experiments was buffered at \u394FMQ 48 \u20130.5 using double capsules and either fayalite-magnetite-quartz (FMQ) or nickel-nickel oxide (NNO) buffers. At the investigated P\u2013T\u2013fO2 conditions, the dominant aqueous dissolution product is carbon dioxide, formed by oxidation of solid carbon. At 1 GPa and 800\ub0C, oxidative dissolution of glass-like carbon produces 16\u201319 mol% more carbon dioxide than crystalline graphite. In contrast, fluids interacting with glass-like carbon at the higher pressure of 3 GPa show only a limited increase in CO2 (fH2NNO) or even a lower CO2 content (fH2FMQ) with respect to fluids interacting with crystalline graphite. The measured fluid compositions allowed retrieving the difference in Gibbs free energy (\u394G) between glass-like carbon and graphite, which is +1.7(1) kJ/mol at 1 GPa\u2013800\ub0C and +0.51(1) kJ/mol (fH2NNO) at 3 GPa\u2013800\ub0C. Thermodynamic modeling suggests that the decline in dissolution susceptibility at high pressure is related to the higher compressibility of glass-like carbon with respect to crystalline graphite, resulting in G\u2013P curves crossing at about 3.4 GPa at 800\ub0C, close to the graphite\u2013diamond transition. The new experimental data suggest that, in the presence of aqueous fluids that flush subducted sediments, the removal of poorly crystalline \u201cdisordered\u201d graphitic carbon is more efficient than that of crystalline graphite especially at shallow levels of subduction zones, where the difference in free energy is higher and the availability of poorly organized metastable carbonaceous matter and of aqueous fluids produced by devolatilization of the downgoing slab is maximized. At depths greater than 110 km, the small differences in \u394G imply that there is minimal energetic drive for transforming \u201cdisordered\u201d graphitic carbon to ordered graphite; \u201cdisordered\u201d graphitic carbon could even be energetically slightly favored in a narrow P interval

Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir/Abacavir/Lamivudine in Antiretroviral-Naive Adults (SYMTRI): A Multicenter Randomized Open-Label Study (PReEC/RIS-57)

Background. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) is the reference for combination therapy based on protease inhibitors due to its efficacy, tolerability, and convenience. Head-to-head randomized comparisons between D/C/F/TAF and combination therapy based on integrase inhibitors in antiretroviral-naive patients are lacking. Methods. Adult (>18 years old) human immunodeficiency virus-infected antiretroviral-naive patients (HLA-B∗5701 negative and hepatitis B virus negative), with viral load (VL) ≥500 c/mL, were centrally randomized to initiate D/C/F/TAF or dolutegravir/ abacavir/lamivudine (DTG/3TC/ABC) after stratifying by VL and CD4 count. Clinical and analytical assessments were performed at weeks 0, 4, 12, 24, and 48. The primary endpoint was VL <50 c/mL at week 48 in the intention-to-treat (ITT)-exposed population (US Food and Drug Administration snapshot analysis, 10% noninferiority margin). Results. Between September 2018 and 2019, 316 patients were randomized and 306 patients were included in the ITT-exposed analysis (151 D/C/F/TAF and 155 DTG/3TC/ABC). Almost all (94%) participants were male and their median age was 35 years. Forty percent had a baseline VL >100 000 copies/mL, and 13% had <200 CD4 cells/μL. Median weight was 73 kg and median body mass index was 24 kg/m2 . At 48 weeks, 79% (D/C/F/TAF) versus 82% (DTG/3TC/ABC) had VL <50 c/mL (difference, −2.4%; 95% confidence interval [CI], −11.3 to 6.6). Eight percent versus four percent experienced virologic failure but no resistance-associated mutations emerged. Four percent versus six percent had drug discontinuation due to adverse events. In the per-protocol analysis, 94% versus 96% of patients had VL <50 c/mL (difference, −2%; 95% CI, −8.1 to 3.5). There were no differences in CD4 cell count or weight changes. Conclusions. We could not demonstrate the noninferiority of D/C/F/TAF relative to DTG/ABC/3TC as initial antiretroviral therapy, although both regimens were similarly well tolerated

Subducted organic matter buffered by marine carbonate rules the carbon isotopic signature of arc emissions

Ocean sediments consist mainly of calcium carbonate and organic matter (phytoplankton debris). Once subducted, some carbon is removed from the slab and returns to the atmo- sphere as CO2 in arc magmas. Its isotopic signature is thought to reflect the bulk fraction of inorganic (carbonate) and organic (graphitic) carbon in the sedimentary source. Here we challenge this assumption by experimentally investigating model sediments composed of 13C-CaCO3 + 12C-graphite interacting with water at pressure, temperature and redox con- ditions of an average slab–mantle interface beneath arcs. We show that oxidative dissolution of graphite is the main process controlling the production of CO2, and its isotopic compo- sition reflects the CO2/CaCO3 rather than the bulk graphite/CaCO3 (i.e., organic/inorganic carbon) fraction. We provide a mathematical model to relate the arc CO2 isotopic signature with the fluid–rock ratios and the redox state in force in its subarc source

No Changes in Human Immunodeficiency Virus (HIV) Suppression and Inflammatory Markers in Cerebrospinal Fluid in Patients Randomly Switched to Dolutegravir Plus Lamivudine (Spanish HIV/AIDS Research Network, PreEC/RIS 62)

A major concern of HIV dual therapy is a potential lower efficacy in viral reservoirs, especially in the central nervous system (CNS). We evaluated HIV RNA, neuronal injury and inflammatory biomarkers and dolutegravir (DTG) exposure in cerebrospinal fluid (CSF) in patients switching to DTG+lamivudine (3TC). All participants maintained viral suppression in plasma and CSF at week 48. We observed no increase in CSF markers of inflammation or neuronal injury. Median (IQR) total and unbound DTG in CSF were 7.3(5.9-8.4) ng/mL and 1.7(1.2-1.9) ng/mL, respectively. DTG+3TC may maintain viral control without changes in inflammatory/injury markers within the CNS reservoir

A Target Animal Effectiveness Study on Adjuvant Peptide-Based Vaccination in Dogs with Non-Metastatic Appendicular Osteosarcoma Undergoing Amputation and Chemotherapy

Despite efforts to develop novel treatment strategies, human and canine osteosarcomas continue to have poor prognosis and limited overall survival. The aim of this clinical trial was to test the antitumor effect and safety of multiple dermal administrations of a peptide-based anticancer vaccine in dogs with non-metastatic appendicular osteosarcoma undergoing standard of care (SOC), consisting of limb amputation and adjuvant chemotherapy. Salmonella-infected canine osteosarcoma cells were induced to release immunogenic peptides in the extracellular space via Cx43 hemichannels opening; the secretome was collected and constituted the vaccine. Dogs with non-metastatic appendicular osteosarcoma were eligible for recruitment. Following limb amputation and adjuvant carboplatin, dogs were vaccinated on a monthly basis for six times and followed up with serial thoracic radiographs. A population of dogs undergoing SOC treatment (amputation and adjuvant carboplatin) before the vaccine was available served as controls. Primary endpoints were time to metastasis (TTM) and tumor-specific survival (TSS). Secondary endpoints were feasibility, toxicity, T-cell and humoral immune responses. A total of 20 dogs were vaccinated along with SOC and 34 received SOC only. Vaccine-specific humoral and T-cell responses were observed; their amplitude correlated with TSS. Vaccine-associated toxicity was not recorded. TTM and TSS were significantly longer in vaccinated versus unvaccinated dogs (TTM: 308 vs. 240 days, respectively; p = 0.010; TSS: 621 vs. 278 days, respectively; p = 0.002). In dogs with non-metastatic osteosarcoma undergoing SOC, the addition of a bacteria-based vaccination strategy increased TTM, thereby prolonging survival, while maintaining a safe profile. Additionally, vaccinated dogs developed a long-term tumor-specific response, as documented by the immunomonitoring of these patients over time. These results hold promise for future management of canine osteosarcoma

Environmental consequences of Ontong Java Plateau and Kerguelen Plateau Volcanism

The mid-Cretaceous was marked by emplacement of large igneous provinces (LIPs) that formed gigantic oceanic plateaus, affecting ecosystems on a global scale, with biota forced to face excess CO2 resulting in climate and ocean perturbations. Volcanic phases of the Ontong Java Plateau (OJP) and the southern Kerguelen Plateau (SKP) are radiometrically dated and correlate with paleoenvironmental changes, suggesting causal links between LIPs and ecosystem responses. Aptian biocalcifi cation crises and recoveries are broadly coeval with C, Pb, and Os isotopic anomalies, trace metal infl uxes, global anoxia, and climate changes. Early Aptian greenhouse or supergreenhouse conditions were followed by prolonged cooling during the late Aptian, when OJP and SKP developed, respectively. Massive volcanism occurring at equatorial versus high paleolatitudes and submarine versus subaerial settings triggered very different climate responses but similar disruptions in the marine carbonate system. Excess CO2 arguably induced episodic ocean acidifi cation that was detrimental to marine calcifi ers, regardless of hot or cool conditions. Global anoxia was reached only under extreme warming, whereas cold conditions kept the oceans well oxygenated even at times of intensifi ed fertility. The environmental disruptions attributed to the OJP did not trigger a mass extinction: rock-forming nannoconids and benthic communities underwent a signifi cant decline during Oceanic Anoxic Event (OAE) 1a, but recovered when paroxysmal volcanism fi nished. Extinction of many planktonic foraminiferal and nannoplankton taxa, including most nannoconids, and most aragonitic rudists in latest Aptian time was likely triggered by severe ocean acidifi cation. Upgraded dating of paleoceanographic events, improved radiometric ages of the OJP and SKP, and time-scale revision are needed to substantiate the links between magmatism and paleoenvironmental perturbations

123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography and 123I-metaiodobenzylguanidine myocardial scintigraphy in differentiating dementia with lewy bodies from other dementias: A comparative study

Objective: To compare the diagnostic value of striatal 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) single photon emission computed tomography (SPECT) and 123I-metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy in differentiating dementia with Lewy bodies (DLB) from other dementia types. Methods: This prospective longitudinal study included 30 patients with a clinical diagnosis of DLB and 29 patients with non-DLB dementia (Alzheimer disease, n = 16; behavioral variant frontotemporal dementia, n = 13). All patients underwent 123I-FP-CIT SPECT and 123I-MIBG myocardial scintigraphy within a few weeks of clinical diagnosis. All diagnoses at each center were agreed upon by the local clinician and an independent expert, both unaware of imaging data, and re-evaluated after 12 months. Each image was visually classified as either normal or abnormal by 3 independent nuclear physicians blinded to patients' clinical data. Results: Overall, sensitivity and specificity to DLB were respectively 93% and 100% for 123I-MIBG myocardial scintigraphy, and 90% and 76% for 123I-FP-CIT SPECT. Lower specificity of striatal compared to myocardial imaging was due to decreased 123I-FP-CIT uptake in 7 non-DLB subjects (3 with concomitant parkinsonism) who had normal 123I-MIBG myocardial uptake. Notably, in our non-DLB group, myocardial imaging gave no false-positive readings even in those subjects (n = 7) with concurrent medical illnesses (diabetes and/or heart disease) supposed to potentially interfere with 123I-MIBG uptake. Interpretation: 123I-FP-CIT SPECT and 123I-MIBG myocardial scintigraphy have similar sensitivity for detecting DLB, but the latter appears to be more specific for excluding non-DLB dementias, especially when parkinsonism is the only “core feature” exhibited by the patient. Our data also indicate that the potential confounding effects of diabetes and heart disease on 123I-MIBG myocardial scintigraphy results might have been overestimated. Ann Neurol 2016;80:368–378

Labor market reform and rent-sharing : a quasi-experiment experience

We analyze the impact on wages of the adoption of a rent-sharing remuneration scheme aiming at making labor institutions more flexible. We are working with a quasi- experimental setting referring to a sample of Italian companies before and after the introduction of the Treu Reform (1997). Our estimations confirm that this reform not only increased insider workers' wages via rent-sharing, but also fueled a s-convergence process of the rent-sharing elasticity across the sectors at a different rate. Finally, we deliver a reasoned discussion of the consequences at large of the implementation of this reform in the Italian job market