1,013 research outputs found
Correlation between the bath composition and nanoporosity of DC-electrodeposited Ni-Fe alloy
The outstanding mechanical strength of as-deposited DC-electrodeposited nanocrystalline (nc) Ni-Fe alloys has been the subject of numerous researches in view of their scientific and practical interest. However, recent studies have reported a dramatic drop in ductility upon annealing above 350°C, associated with a concomitant abnormal rapid grain growth. The inherent cause has been ascribed to the presence of a detrimental product or by product in the bath, which affects either the microstructure or causes defects in the concentration and/or distribution of the as-deposited films. The present work has been inspired by the observed abnormal behaviour of annealed electrodeposited nc Ni-Fe alloy, which has here been addressed by considering the relationship between the composition of the bath (iron-chloride, nickel-sulphate solution, saccharin and ascorbic acid) and deposition defects (e.g. grain boundary pores) in the case of an nc Ni-Fe (Fe 48 wt%) alloy. The current investigations have included X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM) in both as-deposited and post-annealed conditions (300°C–400°C). XPS depth profiling with Ar ion sputtering showed a significant amount of C and O impurities entrapped in the foils during deposition. As such impurities are often overlooked in common analytical techniques, new scenarios may need to be rationalised to explain the observed drop in tensile ductility of the as-deposited Ni-Fe alloys
New insulin glargine 300 U/ml compared with glargine 100 U/ml in insulin-naïve people with type 2 diabetes on oral glucose-lowering drugs:a randomized controlled trial (EDITION 3)
AIMS: To compare the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with that of glargine 100 U/ml (Gla-100) in insulin-naïve people with type 2 diabetes using oral glucose-lowering drugs. METHODS: The EDITION 3 study was a multicentre, open-label, parallel-group study. Participants were randomized to Gla-300 or Gla-100 once daily for 6 months, discontinuing sulphonylureas and glinides, with a dose titration aimed at achieving pre-breakfast plasma glucose concentrations of 4.4–5.6 mmol/l (80–100 mg/dl). The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to month 6. The main secondary endpoint was percentage of participants with ≥1 nocturnal confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemia from week 9 to month 6. Other measures of glycaemia and hypoglycaemia, weight change and insulin dose were assessed. RESULTS: Randomized participants (n = 878) had a mean (standard deviation) age of 57.7 (10.1) years, diabetes duration 9.8 (6.4) years, body mass index 33.0 (6.7) kg/m(2) and HbA1c 8.54 (1.06) % [69.8 (11.6) mmol/mol]. HbA1c levels decreased by equivalent amounts with the two treatments; the least squares mean difference in change from baseline was 0.04 [95% confidence interval (CI) −0.09 to 0.17] % or 0.4 (−1.0 to 1.9) mmol/mol. Numerically fewer participants reported ≥1 nocturnal confirmed (≤3.9 mmol/l) or severe hypoglycaemia from week 9 to month 6 [relative risk (RR) 0.89 (95% CI 0.66 to 1.20)] with Gla-300 versus Gla-100; a significantly lower risk of hypoglycaemia with this definition was found over the 6-month treatment period [RR 0.76 (95% CI 0.59 to 0.99)]. No between-treatment differences in adverse events were identified. CONCLUSIONS: Gla-300 is as effective as Gla-100 in reducing HbA1c in insulin-naïve people with type 2 diabetes, with lower hypoglycaemia risk
Glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus insulin glargine 100 U/ml in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs: the EDITION 2 randomized 12-month trial including 6-month extension
Peer reviewe
Antenna beam characterisation for the global 21cm experiment LEDA and its impact on signal model parameter reconstruction
Cosmic Dawn, the onset of star formation in the early universe, can in
principle be studied via the 21cm transition of neutral hydrogen, for which a
sky-averaged absorption signal, redshifted to MHz frequencies, is predicted to
be {\it O}(10-100)\,mK. Detection requires separation of the 21cm signal from
bright chromatic foreground emission due to Galactic structure, and the
characterisation of how it couples to instrumental response. In this work, we
present characterisation of antenna gain patterns for the Large-aperture
Experiment to detect the Dark Ages (LEDA) via simulations, assessing the
effects of the antenna ground-plane geometries used, and measured soil
properties. We then investigate the impact of beam pattern uncertainties on the
reconstruction of a Gaussian absorption feature. Assuming the pattern is known
and correcting for the chromaticity of the instrument, the foregrounds can be
modelled with a log-polynomial, and the 21cm signal identified with high
accuracy. However, uncertainties on the soil properties lead to
\textperthousand\ changes in the chromaticity that can bias the signal
recovery. The bias can be up to a factor of two in amplitude and up to few \%
in the frequency location. These effects do not appear to be mitigated by
larger ground planes, conversely gain patterns with larger ground planes
exhibit more complex frequency structure, significantly compromising the
parameter reconstruction. Our results, consistent with findings from other
antenna design studies, emphasise the importance of chromatic response and
suggest caution in assuming log-polynomial foreground models in global signal
experiments.Comment: Accepted for publication in MNRA
Targeted Repolarization of Tumor‐Associated Macrophages via Imidazoquinoline‐Linked Nanobodies
Non-surface mass balance of glaciers in Iceland
Publisher's version (útgefin grein)Non-surface mass balance is non-negligible for glaciers in Iceland. Several Icelandic glaciers are in the neo-volcanic zone where a combination of geothermal activity, volcanic eruptions and geothermal heat flux much higher than the global average lead to basal melting close to 150 mm w.e. a−1 for the Mýrdalsjökull ice cap and 75 mm w.e. a−1 for the largest ice cap, Vatnajökull. Energy dissipation in the flow of water and ice is also rather large for the high-precipitation, temperate glaciers of Iceland resulting in internal and basal melting of 20–150 mm w.e. a−1. The total non-surface melting of glaciers in Iceland in 1995–2019 was 45–375 mm w.e. a−1 on average for the main ice caps, and was largest for Mýrdalsjökull, the south side of Vatnajökull and Eyjafjallajökull. Geothermal melting, volcanic eruptions and the energy dissipation in the flow of water and ice, as well as calving, all contribute, and thus these components should be considered in mass-balance studies. For comparison, the average mass balance of glaciers in Iceland since 1995 is −500 to −1500 mm w.e. a−1. The non-surface mass balance corresponds to a total runoff contribution of 2.1 km3 a−1 of water from Iceland.Financial support for lidar mapping of glaciers in Iceland in 2008–2012 was provided by the Icelandic Research Fund (163391-052), the Landsvirkjun (National Power Company of Iceland) Research Fund, the Icelandic Road Administration, the Reykjavík Energy Environmental and Energy Research Fund, the National Land Survey of Iceland, the Klima- og Luftgruppen (KoL) research fund of the Nordic Council of Ministers, and the Vatnajökull National Park. The acquisition of the Hofsjökull 2013 DEM was funded by AlpS GmbH and the University of Innsbruck. The acquisition of the Langjökull 2013 DEM was funded by NERC grant IG 13/12 and the DEM was provided by Ian Willis at the Scott Polar Research Institute. The work on estimating geothermal and volcanic power is based on funding from many sources, including the Research Fund of the University of Iceland, ISAVIA (the Icelandic Aviation Service), the Icelandic Road Administration and Landsvirkjun; logistical support has been provided by the Iceland Glaciological Society.Peer Reviewe
Intravenous sodium nitrite in acute ST-elevation myocardial infarction: a randomized controlled trial (NIAMI).
AIM: Despite prompt revascularization of acute myocardial infarction (AMI), substantial myocardial injury may occur, in part a consequence of ischaemia reperfusion injury (IRI). There has been considerable interest in therapies that may reduce IRI. In experimental models of AMI, sodium nitrite substantially reduces IRI. In this double-blind randomized placebo controlled parallel-group trial, we investigated the effects of sodium nitrite administered immediately prior to reperfusion in patients with acute ST-elevation myocardial infarction (STEMI).
METHODS AND RESULTS: A total of 229 patients presenting with acute STEMI were randomized to receive either an i.v. infusion of 70 μmol sodium nitrite (n = 118) or matching placebo (n = 111) over 5 min immediately before primary percutaneous intervention (PPCI). Patients underwent cardiac magnetic resonance imaging (CMR) at 6-8 days and at 6 months and serial blood sampling was performed over 72 h for the measurement of plasma creatine kinase (CK) and Troponin I. Myocardial infarct size (extent of late gadolinium enhancement at 6-8 days by CMR-the primary endpoint) did not differ between nitrite and placebo groups after adjustment for area at risk, diabetes status, and centre (effect size -0.7% 95% CI: -2.2%, +0.7%; P = 0.34). There were no significant differences in any of the secondary endpoints, including plasma troponin I and CK area under the curve, left ventricular volumes (LV), and ejection fraction (EF) measured at 6-8 days and at 6 months and final infarct size (FIS) measured at 6 months.
CONCLUSIONS: Sodium nitrite administered intravenously immediately prior to reperfusion in patients with acute STEMI does not reduce infarct size
KLF2 mutation is the most frequent somatic change in splenic marginal zone lymphoma and identifies a subset with distinct genotype.
To characterise the genetics of splenic marginal zone lymphoma (SMZL), we performed whole exome sequencing of 16 cases and identified novel recurrent inactivating mutations in Kruppel-like factor 2 (KLF2), a gene whose deficiency was previously shown to cause splenic marginal zone hyperplasia in mice. KLF2 mutation was found in 40 (42%) of 96 SMZLs, but rarely in other B-cell lymphomas. The majority of KLF2 mutations were frameshift indels or nonsense changes, with missense mutations clustered in the C-terminal zinc finger domains. Functional assays showed that these mutations inactivated the ability of KLF2 to suppress NF-κB activation by TLR, BCR, BAFFR and TNFR signalling. Further extensive investigations revealed common and distinct genetic changes between SMZL with and without KLF2 mutation. IGHV1-2 rearrangement and 7q deletion were primarily seen in SMZL with KLF2 mutation, while MYD88 and TP53 mutations were nearly exclusively found in those without KLF2 mutation. NOTCH2, TRAF3, TNFAIP3 and CARD11 mutations were observed in SMZL both with and without KLF2 mutation. Taken together, KLF2 mutation is the most common genetic change in SMZL and identifies a subset with a distinct genotype characterised by multi-genetic changes. These different genetic changes may deregulate various signalling pathways and generate cooperative oncogenic properties, thereby contributing to lymphomagenesis.The research was supported by grants from Leukaemia & Lymphoma Research, U.K., Addenbrooke’s Charitable Trust. SM is a PhD student supported by MRC and Department of Pathology, University of Cambridge. LEI is a PhD student supported by the Pathological Society of UK & Ireland. NB is a fellow of the European Hematology Association and was supported by a starter grant from the Academy of Medical Sciences
Comprehensive detection of recurring genomic abnormalities : a targeted sequencing approach for multiple myeloma
Recent genomic research efforts in multiple myeloma have revealed clinically relevant molecular subgroups beyond conventional cytogenetic classifications. Implementing these advances in clinical trial design and in routine patient care requires a new generation of molecular diagnostic tools. Here, we present a custom capture next-generation sequencing (NGS) panel designed to identify rearrangements involving the IGH locus, arm level, and focal copy number aberrations, as well as frequently mutated genes in multiple myeloma in a single assay. We sequenced 154 patients with plasma cell disorders and performed a head-to-head comparison with the results from conventional clinical assays, i.e., fluorescent in situ hybridization (FISH) and single-nucleotide polymorphism (SNP) microarray. Our custom capture NGS panel had high sensitivity (>99%) and specificity (>99%) for detection of IGH translocations and relevant chromosomal gains and losses in multiple myeloma. In addition, the assay was able to capture novel genomic markers associated with poor outcome such as bi-allelic events involving TP53. In summary, we show that a multiple myeloma designed custom capture NGS panel can detect IGH translocations and CNAs with very high concordance in relation to FISH and SNP microarrays and importantly captures the most relevant and recurrent somatic mutations in multiple myeloma rendering this approach highly suitable for clinical application in the modern era
Tests at 2K of the beta 0.35 spoke cryomodule prototype with the MTCA.4-based Low Level RF system prototype for the MYRRHA R&D
Within the framework of the first phase of MYRRHA (Multi-purpose hYbrid
Research Reactor for High-tech Applications) project, called MINERVA, IJCLab
was in charge of a fully equipped Spoke cryomodule prototype development,
tested at 2K. It integrates two superconducting single spoke cavities, the RF
power couplers and the Cold Tuning Systems associated. On the control side, a
MTCA.4-based Low Level Radio Frequency (LLRF) system prototype and the
Software/EPICS developments has been realized by IJCLab and the SCK CEN in
collaboration with the company IOxOS Technologies. The final version of the
global system and the results of the tests at 2K will show with some
perspectives.Comment: Poster pr\'esent\'e au LLRF Workshop 2023 (LLRF2023, arXiv :
2310.03199
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