Evaluation of the Reveal® rapid AST system to assess the susceptibility of Pseudomonas aeruginosa from blood cultures.

This study was set up to assess the performance of the Reveal® rapid AST system to determine the drug susceptibility of Pseudomonas aeruginosa strains directly from blood cultures. Two hundred fully sequenced clinical P. aeruginosa strains were selected for the evaluation, of which 26.5% (n = 53) produced transferable ß-lactamases, and 2.0 to 33.0% had susceptibility levels close to the EUCAST 2021 breakpoints of 11 commonly used antipseudomonal antibiotics. The Reveal® AST system was run with a commercial MIC microplate designed for fast-growing Gram-negative bacilli (Microscan Neg MDR MIC 1), and was compared to the manually operated GN6F MIC microdilution panel from Thermo Fisher, as a comparator method. The Reveal® AST system provided MIC results for the 11 antipseudomonal antibiotics tested within a mean time to result of 6 h 22 min. By comparison with the GN6F panel, the overall rates of categorical agreement (CA), very major errors (VME), major errors (ME), and minor errors (mE for meropenem only) were 96.1%, 1.6%, 4.2%, and 0.6%, respectively. The Specific Reveal® AST system appears to be a reliable and fast technology to determine the susceptibility of P. aeruginosa to antibiotics, including those with resistance levels near categorical breakpoints, directly from blood cultures.

Image texture, low contrast liver lesion detectability and impact on dose: Deep learning algorithm compared to partial model-based iterative reconstruction.

OBJECTIVES: To compare deep learning (True Fidelity, TF) and partial model based Iterative Reconstruction (ASiR-V) algorithm for image texture, low contrast lesion detectability and potential dose reduction. METHODS: Anthropomorphic phantoms (mimicking non-overweight and overweight patient), containing lesions of 6 mm in diameter with 20HU contrast, were scanned at five different dose levels (2,6,10,15,20 mGy) on a CT system, using clinical routine protocols for liver lesion detection. Images were reconstructed using ASiR-V 0% (surrogate for FBP), 60 % and TF at low, medium and high strength. Noise texture was characterized by computing a normalized Noise Power Spectrum filtered by an eye filter. The similarity against FBP texture was evaluated using peak frequency difference (PFD) and root mean square deviation (RMSD). Low contrast detectability was assessed using a channelized Hotelling observer and the area under the ROC curve (AUC) was used as figure of merit. Potential dose reduction was calculated to obtain the same AUC for TF and ASiR-V. RESULTS: FBP-like noise texture was more preserved with TF (PFD from -0.043mm-1 to -0.09mm-1, RMSD from 0.12mm-1 to 0.21mm-1) than with ASiR-V (PFD equal to 0.12 mm-1, RMSD equal to 0.53mm-1), resulting in a sharper image. AUC was always higher with TF than ASIR-V. In average, TF compared to ASiR-V, enabled a radiation dose reduction potential of 7%, 25 % and 33 % for low, medium and high strength respectively. CONCLUSION: Compared to ASIR-V, TF at high strength does not impact noise texture and maintains low contrast liver lesions detectability at significant lower dose.

Prospective multicenter study on personalized and optimized MDCT contrast protocols: results on liver enhancement.

OBJECTIVE: To determine a personalized and optimized contrast injection protocol for a uniform and optimal diagnostic level of liver parenchymal enhancement, in a large patient population enrolled in a multicenter study. METHODS: Six hundred ninety-two patients who underwent a standardized multi-phase liver CT examination were prospectively assigned to one contrast media (CM) protocol group: G1 (100 mL fixed volume, 37 gI); G2 (600 mgI/kg of total body weight (TBW)); G3 (750 mgI/kg of fat-free mass (FFM)), and G4 (600 mgI/kg of FFM). Change in liver parenchyma CT number between unenhanced and contrast-enhanced images was measured by two radiologists, on 3-mm pre-contrast and portal phase axial reconstructions. The enhancement histograms were compared across CM protocols, specifically according to a target diagnostic value of 50 HU. The total amount of iodine dose was also compared among protocols by median and interquartile range (IQR). The Kruskal-Wallis and Mann-Whitney U tests were used to assess significant differences (p < 0.005), as appropriate. RESULTS: A significant difference (p < 0.001) was found across the groups with liver enhancement decreasing from median over-enhanced values of 77.0 (G1), 71.3 (G2), and 65.1 (G3) to a target enhancement of 53.2 HU for G4. Enhancement IQR was progressively reduced from 26.5 HU (G1), 26.0 HU (G2), and 17.8 HU (G3) to 14.5 HU (G4). G4 showed a median iodine dose of 26.0 gI, significantly lower (p < 0.001) than G3 (33.9 gI), G2 (38.8 gI), and G1 (37 gI). CONCLUSIONS: The 600 mgI/kg FFM-based protocol enabled a diagnostically optimized liver enhancement and improved patient-to-patient enhancement uniformity, while significantly reducing iodine load. KEY POINTS: • Consistent and clinically adequate liver enhancement is observed with personalized and optimized contrast injection protocol. • Fat-free mass is an appropriate body size parameter for correlation with liver parenchymal enhancement. • Diagnostic oncology follow-up liver CT examinations may be obtained using 600 mgI/kg of FFM.

Functional signs in patients consulting for presumed Lyme borreliosis.

INTRODUCTION: Little is known about the functional symptoms associated with Lyme borreliosis (LB) in Europe. We aimed to assess functional symptoms associated with presumed LB and to compare patients with and without confirmed LB. MATERIALS AND METHODS: We performed a retrospective monocenter study. Patients consulting for presumed LB were included. RESULTS: Between November 2015 and June 2018, 355patients were included (mean age: 51years, 52% of women) of which 48had LB: erythema migrans (42%), early disseminated LB (50%; 35% of neuroborreliosis cases), and late disseminated LB (8%). The most frequently reported functional symptoms were neuropathic pain (23%), arthralgia (23%), and asthenia (17%). Other functional symptoms were rare (≤10%). Three hundred and seven (86%) patients did not have LB. Patients with confirmed LB reported fewer functional symptoms than patients without LB (1.8 (±1.7) vs. 3.6 (±2.5), P<0.001) with a shorter duration of symptoms (< 3 months in 48% vs. 16% of cases, P<0.001). They less often reported asthenia (17% vs. 59%, P<0.001), widespread pain (10% vs. 31%, P=0.003), myalgia (10% vs. 32%, P=0.002), memory disorders (4% vs. 16%, P=0.03), irritability (2% vs. 23%, P±0.001), and sadness (0% vs. 16%, P=0.003). CONCLUSION: In patients consulting for presumed LB, patients diagnosed with LB had fewer and shorter functional symptoms than patients without LB.

Does the repetition over a short time of a microsurgical suture improve its reliability?

Our hypothesis was that immediate repetition of a microsurgery-suturing task will improve its execution and outcome. This was an experimental animal study. Ten surgeons were divided into two groups of five surgeons. Each performed two end-to-end carotid anastomoses on the same rat, one after the other. The anastomosis was evaluated by the surgeon and an instructor. The primary endpoint was permeability. The outcome was evaluated using an objective and subjective assessment grid yielding 1 to 3 points per item. The total scores for each of the 10 surgeons were used to compare the anastomosis of carotid 1 versus 2, using the ratings given by the surgeon and the instructor. Twenty anastomoses were performed, but 1 rat died intraoperatively, leaving 18 anastomoses for evaluation. No significant differences were found on the main endpoint of permeability, with all anastomoses being permeable. The surgeon's self-assessment was significantly better for the second carotid artery (P=0.05), but this was not confirmed by the proxy assessment (instructor). The analysis by subgroups-morning versus afternoon-found the second carotid anastomosis was significant better in the self-assessment and proxy assessment for the morning group (P<0.001, P=0.024). There was no significant difference in clamping times. The immediate repetition of a microsurgical procedure seems to favor its execution, which leads us to propose that the more difficult or important anastomosis should be done after an easier or less important one during complex surgeries. LEVEL OF EVIDENCE: 2B.

Synthesis and characterization of single-phase epitaxial Cr2N thin films by reactive magnetron sputtering.

Cr2N is commonly found as a minority phase or inclusion in stainless steel, CrN-based hard coatings, etc. However, studies on phase-pure material for characterization of fundamental properties are limited. Here, Cr2N thin films were deposited by reactive magnetron sputtering onto (0001) sapphire substrates. X-ray diffraction and pole figure texture analysis show Cr2N (0001) epitaxial growth. Scanning electron microscopy imaging shows a smooth surface, while transmission electron microscopy and X-ray reflectivity show a uniform and dense film with a density of 6.6 g cm-3, which is comparable to theoretical bulk values. Annealing the films in air at 400 °C for 96 h shows little signs of oxidation. Nano-indentation shows an elastic-plastic behavior with H = 18.9 GPa and E r = 265 GPa. The moderate thermal conductivity is 12 W m-1 K-1, and the electrical resistivity is 70 µΩ cm. This combination of properties means that Cr2N may be of interest in applications such as protective coatings, diffusion barriers, capping layers and contact materials.

Time to blood culture positivity: An independent predictor of infective endocarditis and mortality in patients with Staphylococcus aureus bacteraemia.

OBJECTIVES: Time to blood culture positivity (TTP), a routinely available parameter in automated blood culture systems, may be a proxy for infectious burden in patients with bloodstream infections. We aimed to study the association between TTP and infective endocarditis (IE), or death, in patients with Staphylococcus aureus bacteraemia. METHODS: VIRSTA is a multicentre prospective cohort study that included all adult patients with S. aureus bacteraemia in eight university hospitals in France (2009-2011). We analysed data from four centres which collected data on TTP. Regression models were used to study the association between TTP and definite IE (Duke-Li criteria), and 30 day-mortality. RESULTS: We included 587 patients with S. aureus bacteraemia: mean age was 65.3 ± 16.3 years, 420 out of 587 patients (71.6%) were male, 121 out of 587 (20.6%) died, and 42 out of 587 (7.2%) had definite IE. Median TTP of first positive blood culture was 13.7 h (interquartile range 9.9-18). On multivariate analysis, 30-day mortality was associated with TTP ≤13.7 h (74/295 (25.1%) vs. 47/292 (16.1%), p 0.02), as well as old age, McCabe score, methicillin resistance, stroke, pneumonia, and C-reactive protein. TTP was also independently associated with IE, but with a U-shape curve: IE was more common in the first (TTP <10 h, 17/148, 11.5%), and the last (TTP ≥18 h, 8/146, 5.5%) quartiles of TTP, p 0.002. CONCLUSIONS: TTP provides reliable information in patients with S. aureus bacteraemia, on the risk of IE, and prognosis, with short TTP being an independent predictor of death. These data, readily available at no cost, may be used to identify patients who require specific attention.

Straightforward measurement of anisotropic thermal properties of a Bi2Se3 single crystal.

We demonstrate here a simple measurement protocol which allows the thermal properties of anisotropic crystalline materials to be determined. This protocol is validated by the measurement of Bi2Se3, a layered material consisting of covalently bonded sheets with weak van der Waals bonds between each layer, which has highly anisotropic thermal properties. Thermoreflectance microscopy measurements were carried out on a single-crystal Bi2Se3 sample, firstly on the bare sample and then after capping with a 100 nm thick gold layer. Whereas on the bare sample lateral heat diffusion is dominated by the in-plane thermal diffusivity, on the metal-capped substrate heat diffusion perpendicular to the sample surface dominates. Using a simple theoretical model, we show how this double measurement protocol allows the anisotropic thermal conductivity coefficients of bulk Bi2Se3 to be evaluated.

Detection of carbapenemase activity in Pseudomonas aeruginosa by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS).

A new MALDI-TOF MS imipenem hydrolysis assay was developed to optimize detection of carbapenemase-producing strains of Pseudomonas aeruginosa. The method correctly discriminated carbapenemase producers (n=74) from non-producers (n=95) in 99.4% of cases, and successfully detected 100% GES-5 strains (n=5).

Implementing a routine flow cytometry assay for nucleated red blood cell counts in cord blood units.

INTRODUCTION: As required by standards organizations, Héma-Québec Cord Blood Bank performs enumeration of nucleated red blood cells (NRBCs) in cord blood units (CBUs). This study presents the validation and implementation approaches developed to transfer the routine NRBC enumeration from the manual blood film method to a flow cytometric assay. METHODS: The flow cytometry method was adapted from Tsuji (Cytometry, 37, 1999, 291). This assay was validated to assess the specificity, detection limit, repeatability, and reproducibility of the method, including interoperator and interlaboratory testing. Finally, postimplementation follow-up and adjustments were performed for CBU over a 7-month period. RESULTS: Blood film and flow cytometry NRBC enumerations showed a strong correlation (n = 40; Pearson's r correlation = 0.90). Validation was successful as exemplified by the correlation in interlaboratory testing (n = 30; r = 0.98). During implementation, our routine laboratory analyses revealed that CBU with low NRBC content (≤2%), representing 26% of all CBU tested, resulted in 15% of repeated reading and/or staining and was the principal source of nonconformity. Small adjustments in the standard operating procedures (SOPs), including a fixed 200-event setting in the NRBC gate for the second reading of the replicates, have completely solved this issue. CONCLUSION: Flow cytometric NRBC enumerations, now implemented in Héma-Québec Public Cord Blood Bank, is an improvement in the efficiency of our operations by integrating the count for NRBC into our flow cytometry platform.

Mutations in ß-Lactamase AmpC Increase Resistance of Pseudomonas aeruginosa Isolates to Antipseudomonal Cephalosporins.

Mutation-dependent overproduction of intrinsic ß-lactamase AmpC is considered the main cause of resistance of clinical strains of Pseudomonas aeruginosa to antipseudomonal penicillins and cephalosporins. Analysis of 31 AmpC-overproducing clinical isolates exhibiting a greater resistance to ceftazidime than to piperacillin-tazobactam revealed the presence of 17 mutations in the ß-lactamase, combined with various polymorphic amino acid substitutions. When overexpressed in AmpC-deficient P. aeruginosa 4098, the genes coding for 20/23 of these AmpC variants were found to confer a higher (2-fold to >64-fold) resistance to ceftazidime and ceftolozane-tazobactam than did the gene from reference strain PAO1. The mutations had variable effects on the MICs of ticarcillin, piperacillin-tazobactam, aztreonam, and cefepime. Depending on their location in the AmpC structure and their impact on ß-lactam MICs, they could be assigned to 4 distinct groups. Most of the mutations affecting the omega loop, the R2 domain, and the C-terminal end of the protein were shared with extended-spectrum AmpCs (ESACs) from other Gram-negative species. Interestingly, two new mutations (F121L and P154L) were predicted to enlarge the substrate binding pocket by disrupting the stacking between residues F121 and P154. We also found that the reported ESACs emerged locally in a variety of clones, some of which are epidemic and did not require hypermutability. Taken together, our results show that P. aeruginosa is able to adapt to efficacious ß-lactams, including the newer cephalosporin ceftolozane, through a variety of mutations affecting its intrinsic ß-lactamase, AmpC. Data suggest that the rates of ESAC-producing mutants are ≥1.5% in the clinical setting.

Thermoresponsive self-assembled cyclodextrin-end-decorated PNIPAM for aqueous catalysis.

The catalytic performance of thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) functionalized at the terminal position with randomly methylated ß-cyclodextrin was demonstrated by the aqueous Rh-catalysed hydroformylation of higher olefins.

Cost effectiveness of newborn screening for cystic fibrosis: a simulation study.

BACKGROUND: Early detection of cystic fibrosis (CF) by newborn screening (NBS) reduces the rate of avoidable complications. NBS protocols vary by jurisdiction and the cost effectiveness of these different protocols is debated. OBJECTIVE: To compare the cost effectiveness of various CF NBS options. METHODS: A Markov model was built to simulate the cost effectiveness of various CF-NBS options for a hypothetical CF-NBS program over a 5-year time horizon assuming its integration into an existing universal NBS program. NBS simulated options were based on a combination of tests between the two commonly used immunoreactive trypsinogen (IRT) cutoffs (96th percentile and 99.5th percentile) as first tier tests, and, as a second tier test, either a second IRT, pancreatic-associated protein (PAP) or CFTR mutation panels. CFTR mutation panels were also considered as an eventual third tier test. Data input parameters used were retrieved from a thorough literature search. Outcomes considered were the direct costs borne by the Quebec public health care system and the number of cases of CF detected through each strategy, including the absence of screening option. RESULTS: IRT-PAP with an IRT cutoff at the 96th percentile is the most favorable option with a ratio of CAD$28,432 per CF case detected. The next most favorable alternative is the IRT1-IRT2 option with an IRT1 cutoff at the 96th percentile. The no-screening option is dominated by all NBS screening protocols considered. Results were robust in sensitivity analyses. CONCLUSION: This study suggests that NBS for cystic fibrosis is a cost-effective strategy compared to the absence of NBS. The IRT-PAP newborn screening algorithm with an IRT cutoff at the 96th percentile is the most cost effective NBS approach for Quebec.

Surface-enhanced charge-density-wave instability in underdoped Bi2Sr(2-x)La(x)CuO(6+δ).

Neutron and X-ray scattering experiments have provided mounting evidence for spin and charge ordering phenomena in underdoped cuprates. These range from early work on stripe correlations in Nd-LSCO to the latest discovery of charge-density-waves in YBa2Cu3O(6+x). Both phenomena are characterized by a pronounced dependence on doping, temperature and an externally applied magnetic field. Here, we show that these electron-lattice instabilities exhibit also a previously unrecognized bulk-surface dichotomy. Surface-sensitive electronic and structural probes uncover a temperature-dependent evolution of the CuO2 plane band dispersion and apparent Fermi pockets in underdoped Bi2 Sr(2-x) La(x) CuO(6+δ) (Bi2201), which is directly associated with an hitherto-undetected strong temperature dependence of the incommensurate superstructure periodicity below 130 K. In stark contrast, the structural modulation revealed by bulk-sensitive probes is temperature-independent. These findings point to a surface-enhanced incipient charge-density-wave instability, driven by Fermi surface nesting. This discovery is of critical importance in the interpretation of single-particle spectroscopy data, and establishes the surface of cuprates and other complex oxides as a rich playground for the study of electronically soft phases.

Alternatives to carbapenems in ESBL-producing Escherichia coli infections.

OBJECTIVES: The authors had for objective to assess the activity of a wide panel of antibiotics on extended-spectrum-ß-lactamase producing Escherichia coli isolates (ESBL-Ec), because of the sharp increase of their frequency, leading to an increased use of carbapenems. MATERIAL AND METHODS: We selected 100 ESBL-Ec in which ESBLs were identified by PCR and sequencing, between 2009 and 2010. We determined the MICs of amoxicillin-clavulanate, piperacillin-tazobactam, temocillin, mecillinam, cefoxitin, cefotaxime, ceftazidime, aztreonam, tigecycline, nitrofurantoin, and fosfomycin using reference methods. The susceptibility profiles were defined according to EUCAST 2012 recommendations. RESULTS: Fosfomycin, nitrofurantoin, and pivmecillinam were active against more than 90% of isolates and remain excellent choices for the oral treatment of urinary tract infections (UTIs). Temocillin and piperacillin-tazobactam are also good candidates for the treatment of pyelonephritis or bloodstream infections. Only 27, 23, and 8% of isolates were susceptible to ceftazidime, cefepime, and cefotaxime, respectively. CONCLUSION: Our study results prove that in many cases, there are non-carbapenem alternatives for the treatment of ESBL-Ec infections.

Minimising pain in farm animals: the 3S approach - 'Suppress, Substitute, Soothe'.

Recently, the French National Institute for Agricultural Research appointed an expert committee to review the issue of pain in food-producing farm animals. To minimise pain, the authors developed a '3S' approach accounting for 'Suppress, Substitute and Soothe' by analogy with the '3Rs' approach of 'Reduction, Refinement and Replacement' applied in the context of animal experimentation. Thus, when addressing the matter of pain, the following steps and solutions could be assessed, in the light of their feasibility (technical constraints, logistics and regulations), acceptability (societal and financial aspects) and availability. The first solution is to suppress any source of pain that brings no obvious advantage to the animals or the producers, as well as sources of pain for which potential benefits are largely exceeded by the negative effects. For instance, tail docking of cattle has recently been eliminated. Genetic selection on the basis of resistance criteria (as e.g. for lameness in cattle and poultry) or reduction of undesirable traits (e.g. boar taint in pigs) may also reduce painful conditions or procedures. The second solution is to substitute a technique causing pain by another less-painful method. For example, if dehorning cattle is unavoidable, it is preferable to perform it at a very young age, cauterising the horn bud. Animal management and constraint systems should be designed to reduce the risk for injury and bruising. Lastly, in situations where pain is known to be present, because of animal management procedures such as dehorning or castration, or because of pathology, for example lameness, systemic or local pharmacological treatments should be used to soothe pain. These treatments should take into account the duration of pain, which, in the case of some management procedures or diseases, may persist for longer periods. The administration of pain medication may require the intervention of veterinarians, but exemptions exist where breeders are allowed to use local anaesthesia (e.g. castration and dehorning in Switzerland). Extension of such exemptions, national or European legislation on pain management, or the introduction of animal welfare codes by retailers into their meat products may help further developments. In addition, veterinarians and farmers should be given the necessary tools and information to take into account animal pain in their management decisions.

Structural origin of apparent Fermi surface pockets in angle-resolved photoemission of Bi2Sr(2-x)La(x)CuO(6+δ).

We observe apparent hole pockets in the Fermi surfaces of single-layer Bi-based cuprate superconductors from angle-resolved photoemission. From detailed low-energy electron diffraction measurements and an analysis of the angle-resolved photoemission polarization dependence, we show that these pockets are not intrinsic but arise from multiple overlapping superstructure replicas of the main and shadow bands. We further demonstrate that the hole pockets reported recently from angle-resolved photoemission [Meng et al., Nature (London) 462, 335 (2009)] have a similar structural origin and are inconsistent with an intrinsic hole pocket associated with the electronic structure of a doped CuO2 plane.

River and estuary movements of yellow-stage American eels Anguilla rostrata, using a hydrophone array.

Patterns of summertime movement and habitat use of yellow-stage American eels Anguilla rostrata within York River and estuary and Gaspé Bay (Gaspesia, Québec, Canada) were examined using acoustic telemetry. Fifty fish were tagged with acoustic transmitters and released, either in the river or in the upper estuary, and their patterns of movement and habitat use were monitored at short spatial and temporal scales during the summer months using a dense hydrophone array. Approximately half of the fish released in the river swam to the estuary; two-thirds of the fish released within the estuary did not move out of the estuary. Anguilla rostrata were detected more frequently and had a greater areal range of detections during night, suggesting greater nocturnal activity. Longitudinal movements within the estuary tended to occur nocturnally, with upstream movements from early to late evening, and downstream movements from late evening to early morning. Approximately one-third of fish showed a regular pattern of movement, tending to reside in the deeper, downstream part of the estuary during day and in the shallower, more upstream part of the estuary during night. Approximately a quarter of fish, located in the upper estuary, remained upstream during both night and day. The remaining fish showed patterns intermediate between these two.

Photothermal heterodyne holography of gold nanoparticles.

We report a method based on heterodyne numerical holography associated to photothermal excitation for full field and three-dimensional localisation of metallic nanoparticles. A modulated pump laser (lambda = 532 nm) heats several particles, creating local refractive index changes. This modulation is detected using a probe and a local oscillator beam (lambda = 785 nm), frequency-shifted to create a hologram beating at low frequency. Tens of particles, down to diameters of 10 nm, can be localised simultaneously and selectively in three dimensions with near- diffraction resolution by a numerical reconstruction of a single hologram acquired in 5 s.