Electricity demand and its typical load pattern are usually affected by many endogenous and exogenous factors to which the generation system must accordingly respond through utility operators. ...Lockdown measures to prevent the spread of COVID-19 imposed by many countries have led to sudden changes in socioeconomic habits which have had direct effects on the electricity systems. Therefore, a detailed analysis of how confinement measures have modified the electricity consumption in Spain, one of the countries most affected by this pandemic, has been performed in this work. Its electricity consumption has decreased by 13.49% from March 14 to April 30, compared to the average value of five previous years. Daily power demand profiles, especially morning and evening peaks, have been modified at homes, hospitals, and in the total power demand. These changes generate a greater uncertainty for the System Operator when making demand forecasts, but production deviations have increased by only 0.1%, thanks to the presence of a diversified generation mix, which has been modified during this period, increasing the proportion of renewable sources and decreasing CO2 emissions.
•Power demand in Spain has decreased by 13.49% due to lockdown measures by COVID-19.•Power demand profiles have changed its usual form on weekdays and weekends.•Average daily deviations in power predictions have only increased by 0.1%.•Renewable power generation has increased during the lockdown.•In March and April 2020, CO2 emissions have decreased by 32.61% compared to 2019.
In this work, we assessed the efficacy and safety of brentuximab vedotin (BV) plus ESHAP (BRESHAP) as second-line therapy for Relapsed/Refractory Hodgkin lymphoma (RRHL) to improve the results before ...autologous stem-cell transplantation (ASCT).
This was a multicenter, open-label, phase I–II trial of patients with RRHL after first-line chemotherapy. Treatment had three 21-day cycles of etoposide, solumedrol, high-dose AraC, and cisplatin. BV was administered at three dose levels (0.9, 1.2, and 1.8 mg/kg) intravenous on day ‒1 to 3 + 3 cohorts of patients. Final BV dose was 1.8 mg/kg. Responding patients proceeded to ASCT, followed by three BV courses (1.8 mg/kg, every 21 days). Main end points for evaluation were maximum tolerable dose and overall and complete response (CR) before ASCT.
A total of 66 patients were recruited (median age 36 years; range 18–66): 40 were primary refractory, 16 early relapse and 10 late relapse. There were 39 severe adverse events were reported in 22 patients, most frequently fever (n = 25, 35% neutropenic), including 3 deaths. Grade 3–4 hematological toxicity presented in 28 cases: neutropenia (n = 21), thrombocytopenia (n = 14), and anemia (n = 7). Grade ≥3–4 extrahematological adverse events (≥5%) were non-neutropenic fever (n = 13) and hypomagnesaemia (n = 3). Sixty-four patients underwent stem-cell mobilization; all collected >2×10e6/kg CD34+ cells (median 5.75; range 2.12–33.4). Overall response before transplant was 91% (CI 84% to 98%), including 70% (CRs 95% CI 59% to 81%). 60 patients were transplanted with no failure engraftments. Post-transplant response was CR in 49 patients (82% CI 73% to 91%) and partial responses in six (10% CI 5% to 15%). After a mean follow-up of 27 months, the 30-month time to treatment to failure was 74% (95% CI 68% to 80%), progression-free survival 71% (95% CI 65% to 77%), and overall survival 91% (CI 84% to 98%).
BRESHAP looks a safe and effective pre-transplant induction regimen, does not jeopardize transplant and allows long-term remissions and survival.
Summary
Background
We have observed an increase in hepatotoxicity (DILI) reporting related to the use of anabolic androgenic steroids (AAS) for bodybuilding.
Aim
To characterise phenotype ...presentation, outcome and severity of AAS DILI.
Methods
Data on 25 cases of AAS DILI reported to the Spanish (20) and Latin‐American (5) DILI Registries were collated and compared with previously published cases.
Results
AAS DILI increased from representing less than 1% of the total cases in the Spanish DILI Registry in the period 2001–2009 to 8% in 2010–2013. Young men (mean age 32 years), requiring hospitalisation, hepatocellular injury and jaundice were predominating features among the AAS cases. AAS DILI caused significantly higher bilirubin values independent of type of damage when compared to other drug classes (P = 0.001). Furthermore, the cholestatic AAS cases presented significantly higher mean peak bilirubin (P = 0.029) and serum creatinine values (P = 0.0002), compared to the hepatocellular cases. In a logistic regression model, the interaction between peak bilirubin values and cholestatic damage was associated with the development of AAS‐induced acute kidney impairment (AKI) OR 1.26 (95% CI: 1.035–1.526); P = 0.021, with 21.5 ×ULN being the best bilirubin cut‐off point for predicting AKI risk (AUCROC 0.92). No fatalities occurred.
Conclusions
Illicit recreational AAS use is a growing cause of reported DILI that can lead to severe hepatic and renal injury. AAS DILI is associated with a distinct phenotype, characterised by considerable bilirubin elevations independent of type of damage. Although hepatocellular injury predominates, acute kidney injury develops in cholestatic cases with pronounced jaundice.
Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are ...mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.
•Fermentative strategy and varietal factors modulated the chemical profile of wines.•The chemometric approach identified potential markers for each fermentative strategy.•EBBAs and cinnamates ...highlighted as markers of sequential fermentations.•2-Phenyl acetate and stone fruit highlighted as markers of spontaneous fermentations.•The fermentative strategies contributed to variability and quality of white wines.
This study evaluates the impact on two varietal white wines from ‘Chardonnay’ and ‘Verdejo’ cultivars of different fermentative strategies: inoculation with Saccharomyces cerevisiae yeast (CT), sequential inoculation (Torulaspora delbrueckii/Saccharomyces cerevisiae) (SI), and spontaneous fermentation (SP). The wines’ chemical composition was characterized by oenological parameters, organic acids, metals, major volatile compounds, ester compounds and sensory analyses. The fermentative strategy (CT, SI and SP) was found to be a key factor for assessing different styles of white wines. SI wines showed enhanced ‘mature fruit’ nuances and a chemical profile characterized by higher content of ethyl propanoate, ethyl isobutyrate and ethyl dihydrocinnamate. Meanwhile, the SP wines presented enhanced “stone fruit” nuances possible related to the higher contents of 2-phenyl acetate and isobutyl acetate. After a chemometric approach the above esters were identified as the markers of each fermentative strategy, independently of the variety.
Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after ...therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of ⩾10
cells/sample, and novel software tools were constructed for automatic plasma cell gating. Multicenter evaluation of 110 follow-up BM from MM patients in very good partial response (VGPR) or CR showed a higher sensitivity for NGF-MRD vs conventional 8-color flow-MRD -MRD-positive rate of 47 vs 34% (P=0.003)-. Thus, 25% of patients classified as MRD-negative by conventional 8-color flow were MRD-positive by NGF, translating into a significantly longer progression-free survival for MRD-negative vs MRD-positive CR patients by NGF (75% progression-free survival not reached vs 7 months; P=0.02). This study establishes EuroFlow-based NGF as a highly sensitive, fully standardized approach for MRD detection in MM which overcomes the major limitations of conventional flow-MRD methods and is ready for implementation in routine diagnostics.
Large peridotite massifs are scattered along the 1500km length of the Yarlung-Zangbo Suture Zone (southern Tibet, China), the major suture between Asia and Greater India. Diamonds occur in the ...peridotites and chromitites of several massifs, together with an extensive suite of trace phases that indicate extremely low fO sub(2) (SiC, nitrides, carbides, native elements) and/or ultrahigh pressures (UHP) (diamond, TiO sub(2) II, coesite, possible stishovite). New physical and isotopic (C, N) studies of the diamonds indicate that they are natural, crystallized in a disequilibrium, high-T environment, and spent only a short time at mantle temperatures before exhumation and cooling. These constraints are difficult to reconcile with previous models for the history of the diamond-bearing rocks. Possible evidence for metamorphism in or near the upper part of the Transition Zone includes the following: (1) chromite (in disseminated, nodular and massive chromitites) containing exsolved pyroxenes and coesite, suggesting inversion from a high-P polymorph of chromite; (2) microstructural studies suggesting that the chromitites recrystallized from fine-grained, highly deformed mixtures of wadsleyite and an octahedral polymorph of chromite; (3) a new cubic Mg-silicate, with the space group of ringwoodite but an inverse-spinel structure (all Si in octahedral coordination); (4) harzburgites with coarsely vermicular symplectites of opx + Cr-Al spinel plus or minus cpx; reconstructions suggest that these are the breakdown products of majoritic garnets, with estimated minimum pressures to>13GPa. Evidence for a shallow pre-metamorphic origin for the chromitites and peridotites includes the following: (1) trace-element data showing that the chromitites are typical of suprasubduction-zone (SSZ) chromitites formed by magma mixing or mingling, consistent with Hf-isotope data from magmatic (375Ma) zircons in the chromitites; (2) the composition of the new cubic Mg-silicate, which suggests a low-P origin as antigorite, subsequently dehydrated; (3) the peridotites themselves, which carry the trace element signature of metasomatism in an SSZ environment, a signature that must have been imposed before the incorporation of the UHP and low-fO sub(2) phases. A proposed P-T-t path involves the original formation of chromitites in mantle-wedge harzburgites, subduction of these harzburgites at c. 375Ma, residence in the upper Transition Zone for >200 Myr, and rapid exhumation at c. 170-150Ma or 130-120Ma. Os-isotope data suggest that the subducted mantle consisted of previously depleted subcontinental lithosphere, dragged down by a subducting oceanic slab. Thermomechanical modeling shows that roll-back of a (much later) subducting slab would produce a high-velocity channelized upwelling that could exhume the buoyant harzburgites (and their chromitites) from the Transition Zone in<10 Myr. This rapid upwelling, which may explain some characteristics of the diamonds, appears to have brought some massifs to the surface in forearc or back-arc basins, where they provided a basement for oceanic crust. This model can reconcile many apparently contradictory petrological and geological datasets. It also defines an important, previously unrecognized geodynamic process that may have operated along other large suture zones such as the Urals.
Summary
G+C mol% content in microorganisms is one of the recommended characteristics for the standard description of bacterial species. In this study we present a novel fluorimetric method to ...estimate the G+C mol% content in microorganisms. Double‐stranded DNA was specifically stained with SYBR Green I, and its thermal denaturalization was followed by measuring a decrease in fluorescence using a real‐time PCR thermocycler. Unlike most previous determinations of G+C mol%, in this study only DNA from microorganisms with an available completely sequenced genome were used to prepare the calibration curves. Calibration curves showed a linear relationship between G+C mol% content and melting temperature and they were performed both in the absence and presence of 30% formamide. This protocol proves to be a rapid and inexpensive method to estimate DNA base ratios of novel microorganisms.
Here we present deep (16 Jy beam−1), very high (40 mas) angular resolution 1.14 mm, polarimetric, Atacama Large Millimeter/submillimeter Array (ALMA) observations toward the massive protostar driving ...the HH 80-81 radio jet. The observations clearly resolve the disk oriented perpendicularly to the radio jet, with a radius of 0 171 (∼291 au at 1.7 kpc distance). The continuum brightness temperature, the intensity profile, and the polarization properties clearly indicate that the disk is optically thick for a radius of R 170 au. The linear polarization of the dust emission is detected almost all along the disk, and its properties suggest that dust polarization is produced mainly by self-scattering. However, the polarization pattern presents a clear differentiation between the inner (optically thick) part of the disk and the outer (optically thin) region of the disk, with a sharp transition that occurs at a radius of ∼0 1 (∼170 au). The polarization characteristics of the inner disk suggest that dust settling has not occurred yet with a maximum dust grain size between 50 and 500 m. The outer part of the disk has a clear azimuthal pattern but with a significantly higher polarization fraction compared to the inner disk. This pattern is broadly consistent with the self-scattering of a radiation field that is beamed radially outward, as expected in the optically thin outer region, although contribution from non-spherical grains aligned with respect to the radiative flux cannot be excluded.
Dalbavancin is a lipoglycopeptide with potent activity against Gram-positive microorganisms, a long half-life, a favorable safety profile, and a high concentration in bone, which makes it an ...interesting alternative for treatment of osteoarticular infections. We performed a multicentric retrospective study of all patients with an osteoarticular infection (septic arthritis, spondylodiscitis, osteomyelitis, or orthopedic implant-related infection) treated with at least one dose of dalbavancin between 2016 and 2017 in 30 institutions in Spain. In order to evaluate the response, patients with or without an orthopedic implant were separated. A total of 64 patients were included.
and
were the most frequent microorganisms. The reasons for switching to dalbavancin were simplification (53.1%), adverse events (25%), or failure (21.9%). There were 7 adverse events, and no patient had to discontinue dalbavancin. In 45 cases, infection was related to an orthopedic implant. The implant material was retained in 23 cases, including that in 15 (65.2%) patients that were classified as cured and 8 (34.8%) that presented improvement. In 21 cases, the implants were removed, including those in 16 (76.2%) cases that were considered successes, 4 (19%) cases were considered improved, and 1 (4.8%) case that was considered a failure. Among the 19 cases without implants, 14 (73.7%) were considered cured, 3 (15.8%) were considered improved, and 2 (10.5%) were considered failures. The results show that dalbavancin is a well-tolerated antibiotic, even when >2 doses are administered, and is associated with a high cure rate. These are preliminary data with a short follow-up; therefore, it is necessary to gain more experience and, in the future, to establish the most appropriate dose and frequency.
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