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Background: Current guidelines recommend that patients with HER2-low metastatic breast cancer (MBC) receive sequentially two antibody–drug conjugates (ADCs): Sacituzumab Govitecan (SG) and Trastuzumab Deruxtecan (T-DXd), despite a similar payload. However, the effectiveness of one after another is unknown. Methods: ADC-Low is a multicentre, retrospective study evaluating the efficacy of SG and T-DXd, one after another, with or without intermediary lines of chemotherapy, in patients with HER2-low MBC. Results: One hundred and seventy-nine patients were included: the majority with HR-negative tumours received SG first (ADC1) (n = 100/108) while most with HR-positive tumours received T-DXd first (n = 56/71). Median progression-free survival 2 was short: 2.7 months (95% CI: 2.4–3.3) in the whole population, respectively, 3.1 (95% CI: 2.6–3.6) and 2.2 months (95% CI: 1.9–2.7) for patients receiving T-DXd or SG second (ADC2). Intermediary lines of chemotherapy between ADC1 and ADC2 had no impact. Primary resistance to ADC2 occurred in 54.4% of patients. Certain patients showed initial response to ADC2. Conclusions: Clinical benefit of sequentially administered SG and T-DXd is limited for most patients. Nevertheless, a subset of patients might benefit—on the short term—from a second ADC. Additional studies are needed to identify patients who could benefit from two ADCs with similar payloads. [ABSTRACT FROM AUTHOR]

We analyze the form factors parametrizing the Bc→ J/ψ, ηc matrix elements of the operators in a generalized low-energy b → c semileptonic Hamiltonian. We consider an expansion in nonrelativistic QCD, classifying the heavy quark spin symmetry breaking terms and expressing the form factors in terms of universal functions in a selected kinematical range. Using as an input the lattice QCD results for the Bc → J/ψ matrix element of the SM operator, we obtain information on other form factors. The extrapolation to the full kinematical range is also presented. [ABSTRACT FROM AUTHOR]

The performance of a new historical reanalysis, the NOAA–CIRES–DOE Twentieth Century Reanalysis version 3 (20CRv3), is evaluated via comparisons with other reanalyses and independent observations. This dataset provides global, 3-hourly estimates of the atmosphere from 1806 to 2015 by assimilating only surface pressure observations and prescribing sea surface temperature, sea ice concentration, and radiative forcings. Comparisons with independent observations, other reanalyses, and satellite products suggest that 20CRv3 can reliably produce atmospheric estimates on scales ranging from weather events to long-term climatic trends. Not only does 20CRv3 recreate a "best estimate" of the weather, including extreme events, it also provides an estimate of its confidence through the use of an ensemble. Surface pressure statistics suggest that these confidence estimates are reliable. Comparisons with independent upper-air observations in the Northern Hemisphere demonstrate that 20CRv3 has skill throughout the twentieth century. Upper-air fields from 20CRv3 in the late twentieth century and early twenty-first century correlate well with full-input reanalyses, and the correlation is predicted by the confidence fields from 20CRv3. The skill of analyzed 500-hPa geopotential heights from 20CRv3 for 1979–2015 is comparable to that of modern operational 3–4-day forecasts. Finally, 20CRv3 performs well on climate time scales. Long time series and multidecadal averages of mass, circulation, and precipitation fields agree well with modern reanalyses and station- and satellite-based products. 20CRv3 is also able to capture trends in tropospheric-layer temperatures that correlate well with independent products in the twentieth century, placing recent trends in a longer historical context. [ABSTRACT FROM AUTHOR]

We provide corrections to section 2, section 4 and appendix A of ref. [1]. We update the numerical results of ref. [1] with the latest results from ref. [2]. [ABSTRACT FROM AUTHOR]

The reaction of a pulsed 18O beam on a 164Dy target was studied in the first experiment with the NuBall array at the IPN Orsay, France. Excited state half-lives were measured using the fast timing method with 20 LaBr3(Ce) detectors. The timing characteristics of the fully digital acquisition system is briefly discussed. A value for the previously unknown half-life of the first excited 4+ state in 178W is presented. [ABSTRACT FROM AUTHOR]

The wavelength used during photochemical grafting of alkene onto silicon related surfaces influences molecular surface coverage. Ultraviolet light leads to apparent highly dense layers on UV absorbing materials due to the side reaction between alkenes resulting in strongly physisorbed dimers whereas higher wavelengths lead to dense and well-controlled layers. [ABSTRACT FROM AUTHOR]

Background In the developed world, kidney transplantation ( KT) in patients with human immunodeficiency virus ( HIV) infection is well established. Developing countries concentrate 90% of the people living with HIV, but their experience is underreported. Regional differences may affect outcomes. Objectives We compared the 3-year outcomes of patients with HIV infection receiving a KT in two different countries, in terms of incomes and development. Methods This was an observational, retrospective, double-center study, including all HIV-infected patients >18 years old undergoing KT. Results Between 2005 and 2015, 54 KTs were performed (39 in a Brazilian center, and 15 in a Spanish center). Brazilians had less hepatitis C virus co-infection (5% vs 27%, P=.024). Median cold ischemia time was higher in Brazil (25 vs 18 hours, P=.001). Biopsy-proven acute rejection ( AR) was higher in Brazil (33% vs 13%, P=.187), as were the number of AR episodes (22 vs 4, P=.063). Patient survival at 3 years was 91.3% in Brazil and 100% in Spain; P=.663. All three cases of death in Brazil were a result of bacterial infections within the first year post transplant. At 3 years, survival free from immunosuppressive changes was lower in Brazil (56% vs 90.9%, P=.036). Raltegravir-based treatment to avoid interaction with calcineurin inhibitor was more prevalent in Spain (80% vs 3%; P<.001). HIV infection remained under control in all patients, with undetectable viral load and no opportunistic infections. Conclusion Important regional differences exist in the demographics and management of immunosuppression and antiretroviral therapy. These details may influence AR and infectious complications. Non- AIDS infections leading to early mortality in Brazil deserve special attention. [ABSTRACT FROM AUTHOR]

Background: Previous studies showed development of daptomycin non-susceptibility (DNS: MIC >4 mg/L) in Enterococcus faecalis infections. However, no studies have assessed the efficacy of the combination of daptomycin/ampicillin against E. faecalis strains developing DNS in the experimental endocarditis (EE) model.Objectives: To assess the in vitro and in vivo efficacy of daptomycin at 10 mg/kg/day, daptomycin/ampicillin and ampicillin/ceftriaxone against two high-level aminoglycoside-resistant E. faecalis strains, one developing DNS after in vitro exposure to daptomycin and another that did not (DS).Methods: Subculture of 82 E. faecalis strains from patients with endocarditis with daptomycin MICs, time-kill and in vivo experiments using the EE model.Results: 33% of the strains (27 of 82) displayed DNS after subculture with daptomycin. Daptomycin MIC rose from 0.5-2 to 8-16 mg/L. In time-kill experiments, when using a high inoculum (10 8 cfu/mL), daptomycin/ampicillin was synergistic for one-third of DS strains and none of DNS strains, while ampicillin/ceftriaxone retained synergy in all cases. In the EE model, daptomycin did not significantly reduce cfu/g from vegetations compared with control against either strain, while daptomycin/ampicillin reduced significantly more cfu/g than daptomycin against the DS strain, but not against the DNS strain [2.9 (2.0-4.1) versus 6.1 (4.5-8.0); P  =   0.002]. Ampicillin/ceftriaxone was synergistic and bactericidal against both strains, displaying the same activity as daptomycin/ampicillin against the DS strain.Conclusions: Performance of an Etest for daptomycin MIC after subculture with daptomycin inhibitory doses on strains of high-level aminoglycoside-resistant E. faecalis endocarditis may be an easy test to predict the in vivo efficacy of daptomycin/ampicillin. [ABSTRACT FROM AUTHOR]

Background The early identification of patients at high risk of severe post liver transplant hepatitis C recurrence is relevant, as these patients may be treated using interferon ( IFN)-free regimens. Methods In a retrospective study with prospectively collected data, we investigated whether the use of several non-invasive methods (fibrosis 4 index [ FIB-4], AST-to-platelets ratio index [ APRI], enhanced liver fibrosis test [ ELF], IFN-γ-inducible protein 10 [ IP-10], and transient elastography by Fibroscan) and their combinations 6 months after transplantation could identify those recipients at higher risk of severe recurrence, defined by the presence of significant fibrosis (F ≥2) and/or portal hypertension (hepatic venous pressure gradient ≥6 mmHg) 12 months after transplant. Seventy-two hepatitis C virus ( HCV)-infected liver transplant patients and 10 recipients in whom HCV was eradicated before transplantation were included in the study. Results The levels of all biomarkers were significantly higher in HCV-infected recipients than in controls. Among HCV recipients, levels of biomarkers were significantly higher in patients with severe recurrence. Although there were no statistically significant differences between biomarkers, APRI, ELF, and FIB-4 obtained the highest area under the ROC curve values. The combination of serum biomarkers with Fibroscan increased the negative and positive predictive values, although diagnostic accuracy of individual tests was not significantly improved. Conclusions Patients at higher risk of severe HCV recurrence can be identified early, 6 months after transplantation, using readily available non-invasive methods. [ABSTRACT FROM AUTHOR]

The study describes significant outcomes of the ‘Metrology for Meteorology’ project, MeteoMet, which is an attempt to bridge the meteorological and metrological communities. The concept of traceability, an idea used in both fields but with a subtle difference in meaning, is at the heart of the project. For meteorology, a traceable measurement is the one that can be traced back to a particular instrument, time and location. From a metrological perspective, traceability further implies that the measurement can be traced back to a primary realization of the quantity being measured in terms of the base units of the International System of Units, the SI. These two perspectives reflect long-standing differences in culture and practice and this project – and this study – represents only the first step towards better communication between the two communities. The 3 year MeteoMet project was funded by the European Metrology Research Program (EMRP) and involved 18 European National Metrological Institutes, 3 universities and 35 collaborating stakeholders including national meteorology organizations, research institutes, universities, associations and instrument companies. The project brought a metrological perspective to several long-standing measurement problems in meteorology and climatology, varying from conventional ground-based measurements to those made in the upper atmosphere. It included development and testing of novel instrumentation as well as improved calibration procedures and facilities, instrument inter comparison under realistic conditions and best practice dissemination. Additionally, the validation of historical temperature data series with respect to measurement uncertainties and a methodology for recalculation of the values were included. [ABSTRACT FROM AUTHOR]

Transplant recipients are at risk of developing Legionnaires' disease ( LD) because of impaired cellular immunity. Here, we describe a renal transplant recipient who developed LD at least 10 days after hospital admission and transplantation. The hospital water network was initially suspected, but further testing determined that the probable source was the patient's domestic water supply. Our report also suggests that the patient's immunosuppressed state may have switched potential colonization to pneumonia. [ABSTRACT FROM AUTHOR]

The robustness and reliability of any climatic assessment, especially those analyzing climate variability and change, depend crucially on the soundness of data and uncertainty associated with measurements. The metrological traceability to national standards of the measurements involved in climate change is a necessary step. This work describes the first attempt to define a fully traceable procedure for the calibration of air-temperature sensors in a special chamber manufactured for this purpose. The facility was designed to calibrate automatic weather stations by comparison with embedded reference standards traceable to temperature and pressure primary standards as maintained in a national metrology institute. The results shown in this paper were obtained through a prototype of the final calibration chamber. An application example of the calibration process is described for the temperature sensor working in the Meteorological Observatory of Moncalieri (Italy) of the Società Meteorologica Italiana where a continuous climate record has been kept since 1865. As result, the data of the historical data series have now associated calibration uncertainties as contributions from the instrument capability, resolution, and calibration procedure adopted. Finally, the possibility of improving climatic analysis, for evaluating climatic trend, by applying calibration corrections to data recorded has been evaluated. The in situ calibration campaign and the resulting differences between the corrected and uncorrected data for the most important quantities considered in the climate analysis, the maximum, minimum, and mean temperatures, are reported. The analysis carried out on a one-year-long observation period shows that the application of the calibration function has an impact on the recorded data. The differences between corrected and uncorrected data are outside the expanded calibration uncertainty, and in a winter season, this effect is more evident. [ABSTRACT FROM AUTHOR]

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The analysis of a large sample of anthracothere remains discovered by the Mission Paléoanthropologique Franco-Tchadienne at Toros-Menalla (TM), Northern Chad, has revealed the occurrence of a single species with a large intraspecific morphological variability. Taxonomic problems triggered the necessity of naming a new species for the TM anthracotheres,Libycosaurus bahrisp. nov. The description of the craniodental remains and the analysis of their variability indicate a marked sexual dimorphism, most probably induced by sex differential growth, helping to reassess the specific diversity ofLibycosaurusand its main evolutionary trends in a phylogenetic perspective. The ecological niche occupied by the new species was also further characterized in its semiaquatic, behavioural, and dietary dimensions. On these grounds we suggest that Late Miocene environmental changes, particularly habitat opening and hydrographic network fragmentation related to increased aridity, played a major role in canalizing semi-aquatic specializations and the extinction of the last African anthracotheres, as well as other bothriodontines. http://zoobank.org/urn:lsid:zoobank.org:pub:8C0AD4BD-952D-4A60-94B8-6F7A23332171 [ABSTRACT FROM AUTHOR]

Availability of long-term and high-quality instrumental climate records is still insufficient and the rich heritage of meteorological surface observations is largely underexploited in many parts of the world. This is particularly striking over the Greater Mediterranean region ( GMR), where meteorological observations have been taken since the 18th century at some locations. The lack of high quality and long series here is despite this region being regarded as a climate change hot spot. This article mainly assesses relevant sources containing Mediterranean historical climate data and metadata either from online repositories worldwide or physical archives, with the emphasis here on the rich holdings kept at French archives. A particular case study is the data rescue ( DARE) program undertaken by the Algerian National Meteorological Service, as well as some of the past and ongoing projects and initiatives aimed at enhancing climate data availability and accessibility over the GMR. Our findings point to the high potential for undertaking DARE activities over the GMR and the need for bringing longer and higher quality climate time series to support a diverse number of scientific and technical assessments and policies. [ABSTRACT FROM AUTHOR]

A workshop was held in Casablanca, Morocco, in March 2012, to enhance knowledge of climate extremes and their changes in the Arab region. This workshop initiated intensive data compilation activities of daily observational weather station data from the Arab region. After conducting careful control processes to ensure the quality and homogeneity of the data, climate indices for extreme temperatures and precipitation were calculated. This study examines the temporal changes in climate extremes in the Arab region with regard to long-term trends and natural variability related to ENSO and NAO. We find consistent warming trends since the middle of the 20th Century across the region. This is evident in the increased frequencies of warm days and warm nights, higher extreme temperature values, fewer cold days and cold nights and shorter cold spell durations. The warming trends seem to be particularly strong since the early 1970s. Changes in precipitation are generally less consistent and characterised by a higher spatial and temporal variability; the trends are generally less significant. However, in the western part of the Arab region, there is a tendency towards wetter conditions. In contrast, in the eastern part, there are more drying trends, although, these are of low significance. We also find some relationships between climate extremes in the Arab region and certain prominent modes of variability, in particular El Niño-Southern Oscillation ( ENSO) and North Atlantic Oscillation ( NAO). The relationships of the climate extremes with NAO are stronger, in general, than those with ENSO, and are particularly strong in the western part of the Arab region (closer to the Atlantic Ocean). The relationships with ENSO are found to be more significant towards the eastern part of the area of study. © 2013 Royal Meteorological Society [ABSTRACT FROM AUTHOR]