Synthesis and Reactivity of Fluorenyl-Tethered N-heterocyclic Stannylenes

N-Heterocyclic stannylenes containing a functionalised donor arm have been synthesised using a transamination strategy from [Sn{N(SiMe3)2}2] and fluorenyl-tethered diamines.</p

NMR data supporting the publication: Synthesis and Reactivity of Fluorenyl-Tethered N-heterocyclic Stannylenes

Zip file containing the raw NMR data for all the new compounds reported in the publication: Synthesis and Reactivity of Fluorenyl-Tethered N-heterocyclic Stannylene

NMR data supporting the publication: Synthesis and Reactivity of Fluorenyl-Tethered N-heterocyclic Stannylenes

Zip file containing the raw NMR data for all the new compounds reported in the publication: Synthesis and Reactivity of Fluorenyl-Tethered N-heterocyclic Stannylene

NHC-stabilized Ru nanoparticles: Synthesis and surface studies

International audienceA family of N-heterocyclic carbene (NHC)-stabilized Ru nanoparticles has been synthesized by using various NHC ligands, including a chiral one. The surface reactivity of the so-obtained RuNHC nanoparticles has been explored after reacting them with CO with the aim to probe the nature and availability of surface metal sites. Hydrogenation catalytic tests were also performed with the RuNHC NPs stabilized by a chiral ligand in order to evaluate their ability in enantioselective catalysis

Epidemiology, species distribution and in vitro antifungal susceptibility of fungaemia in a Spanish multicentre prospective survey

To update the knowledge of the epidemiology of fungaemia episodes in Spain, the species implicated and their in vitro antifungal susceptibilities. Episodes were identified prospectively over 13 months at 44 hospitals. Molecular methods were used to determine the cryptic species inside the Candida parapsilosis and Candida glabrata complexes. Susceptibility to amphotericin B, anidulafungin, caspofungin, fluconazole, flucytosine, itraconazole, micafungin, posaconazole and voriconazole was determined by a microdilution colorimetric method. New species-specific clinical breakpoints (SSCBPs) for echinocandins, fluconazole and voriconazole were applied. The incidence of the 1357 fungaemia episodes evaluated was 0.92 per 1000 admissions. The incidence of Candida albicans fungaemia was the highest (0.41 episodes/1000 admissions), followed by Candida parapsilosis sensu stricto (0.22). Candida orthopsilosis was the fifth cause of fungaemia (0.02), outnumbered by Candida glabrata and Candida tropicalis. Interestingly, the incidence of fungaemia by C. parapsilosis was 11 and 74 times higher than that by C. orthopsilosis and Candida metapsilosis, respectively. Neither Candida nivariensis nor Candida bracarensis was isolated. Fungaemia was more common in non-intensive care unit settings (65.2) and among elderly patients (46.4), mixed fungaemia being incidental (1.5). Overall susceptibility rates were 77.6 for itraconazole, 91.9 for fluconazole and 96.599.8 for the other agents. Important resistance rates were only observed in C. glabrata for itraconazole (24.1) and posaconazole (14.5), and in Candida krusei for itraconazole (81.5). Fungaemia is more common in non-critical patients. C. albicans is the most common species, followed by C. parapsilosis and C. glabrata. Nearly 90 of yeasts are susceptible to all antifungal agents tested. Resistance rates change moderately when applying the new SSCBPs

Understanding the Quantum Computational Speed-up via De-quantisation

While it seems possible that quantum computers may allow for algorithms offering a computational speed-up over classical algorithms for some problems, the issue is poorly understood. We explore this computational speed-up by investigating the ability to de-quantise quantum algorithms into classical simulations of the algorithms which are as efficient in both time and space as the original quantum algorithms. The process of de-quantisation helps formulate conditions to determine if a quantum algorithm provides a real speed-up over classical algorithms. These conditions can be used to develop new quantum algorithms more effectively (by avoiding features that could allow the algorithm to be efficiently classically simulated), as well as providing the potential to create new classical algorithms (by using features which have proved valuable for quantum algorithms). Results on many different methods of de-quantisations are presented, as well as a general formal definition of de-quantisation. De-quantisations employing higher-dimensional classical bits, as well as those using matrix-simulations, put emphasis on entanglement in quantum algorithms; a key result is that any algorithm in which the entanglement is bounded is de-quantisable. These methods are contrasted with the stabiliser formalism de-quantisations due to the Gottesman-Knill Theorem, as well as those which take advantage of the topology of the circuit for a quantum algorithm. The benefits of the different methods are contrasted, and the importance of a range of techniques is emphasised. We further discuss some features of quantum algorithms which current de-quantisation methods do not cover

Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study

Objectives Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis. Setting Prospective, international, multicentre, observational cohort study. Participants Patients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative). Primary outcome 30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality. Results This study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787). Conclusions Patients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups. Trial registration number NCT0432364

Ofatumumab versus Teriflunomide in Multiple Sclerosis

BACKGROUND: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known. METHODS: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume. RESULTS: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P<0.001) and 0.10 and 0.25 in trial 2 (difference, -0.15; 95% CI, -0.20 to -0.09; P<0.001). In the pooled trials, the percentage of patients with disability worsening confirmed at 3 months was 10.9% with ofatumumab and 15.0% with teriflunomide (hazard ratio, 0.66; P = 0.002); the percentage with disability worsening confirmed at 6 months was 8.1% and 12.0%, respectively (hazard ratio, 0.68; P = 0.01); and the percentage with disability improvement confirmed at 6 months was 11.0% and 8.1% (hazard ratio, 1.35; P = 0.09). The number of gadolinium-enhancing lesions per T1-weighted MRI scan, the annualized rate of lesions on T2-weighted MRI, and serum neurofilament light chain levels, but not the change in brain volume, were in the same direction as the primary end point. Injection-related reactions occurred in 20.2% in the ofatumumab group and in 15.0% in the teriflunomide group (placebo injections). Serious infections occurred in 2.5% and 1.8% of the patients in the respective groups. CONCLUSIONS: Among patients with multiple sclerosis, ofatumumab was associated with lower annualized relapse rates than teriflunomide. (Funded by Novartis; ASCLEPIOS I and II ClinicalTrials.gov numbers, NCT02792218 and NCT02792231.)