Proof of concept and feasibility study for preoperative diagnostic use of mixed reality (MR) holograms of individual 3D heart models from standard cardiac computed tomography angiograms (CTA) images. ...Optimal repair for complex congenital heart disease poses high demands on 3D anatomical imagination. Three-dimensional printed heart models are increasingly used for improved morphological understanding during surgical and interventional planning. Holograms are a dynamic and interactive alternative, probably with wider applications.
A 3D heart model was segmented from CTA images in a patient with double outlet right ventricle and transposition of the great arteries (DORV-TGA). The hologram was visualized in the wearable MR platform HoloLens® for 36 paediatric heart team members who filled out a diagnostic and quality rating questionnaire. Morphological and diagnostic output from the hologram was assessed and the 3D experience was evaluated. Locally developed app tools such as hologram rotation, scaling, and cutting were rated. Anatomy identification and diagnostic output was high as well as rating of 3D experience. Younger and female users rated the app tools higher.
This preliminary study demonstrates that MR holograms as surgical planning tool for congenital heart disease may have a high diagnostic value and contribute to understanding complex morphology. The first users experience of the hologram presentation was found to be very positive, with a preference among the female and the younger users. There is potential for improvement of the hologram manipulation tools.
Place cells in hippocampal area CA1 may receive positional information from the intrahippocampal associative network in area CA3 or directly from the entorhinal cortex. To determine whether direct ...entorhinal connections support spatial firing and spatial memory, we removed all input from areas CA3 to CA1, thus isolating the CA1 area. Pyramidal cells in the isolated CA1 area developed sharp and stable place fields. Rats with an isolated CA1 area showed normal acquisition of an associative hippocampal-dependent spatial recognition task. Spatial recall was impaired. These results suggest that the hippocampus contains two functionally separable memory circuits: The direct entorhinal-CA1 system is sufficient for recollection-based recognition memory, but recall depends on intact CA3-CA1 connectivity.
Phoma stem canker is an internationally important disease of oilseed rape (Brassica napus, canola, rapeseed), causing serious losses in Europe, Australia and North America. UK losses of euros 56M per ...season are estimated using national disease survey data and a yield loss formula. Phoma stem canker pathogen populations comprise two main species, Leptosphaeria maculans, associated with damaging stem base cankers, and Leptosphaeria biglobosa, often associated with less damaging upper stem lesions. Both major gene and quantitative trait loci mediated resistance to L. maculans have been identified in B. napus, but little is known about resistance to L. biglobosa. Leptosphaeria maculans, which has spread into areas in North America and eastern Europe where only L. biglobosa was previously identified, now poses a threat to large areas of oilseed rape production in Asia. Epidemics are initiated by air-borne ascospores; major gene resistance to initial infection by L. maculans operates in the leaf lamina of B. napus. It is not clear whether the quantitative trait loci involved in the resistance to the pathogen that can be assessed only at the end of the season operate in the leaf petioles or stems. In countries where serious phoma stem canker epidemics occur, a minimum standard for resistance to L. maculans is included in national systems for registration of cultivars. This review provides a background to a series of papers on improving strategies for managing B. napus resistance to L. maculans, which is a model system for studying genetic interactions between hemi-biotrophic pathogens and their hosts.
•CMR reveals signs of diffuse myocardial fibrosis in young ASO TGA patients.•Extracellular volume fraction was higher in patients compared to controls.•MR marker of diffuse myocardial fibrosis was ...increased in all coronary territories.
Echocardiography is dependent on highly specialized healthcare professionals. Teleoperated examinations could provide higher availability of specialized care for patients living in rural areas. The ...objective of this study was to evaluate the feasibility of a teleoperated robotic echocardiography system.
Twenty-three healthy volunteers underwent teleoperated echocardiography, compared to standard bedside echocardiography. Examination time, image quality, ability to assess cardiac structures, measurements of left ventricular fractional shortening and blood flow velocities were compared. Image quality was rated on a scale from 0 to 3.
Approximately 90% of robotically acquired images were rated as medium quality or better and approximately 80% of cardiac structures were evaluated as assessable by at least one evaluator. Mean image quality was lower for robotic (1.6 ± 0.3) compared to standard clinical examinations (2.5 ± 0.4) (p = 0.001). Left ventricular fractional shortening from the robotic examinations was 2.2%, p = 0.160 (absolute value) lower compared to the reference and showed a variation coefficient of 19%. The calculated Doppler insonation angles deviated from the reference by more than 25° for three of four blood flow velocity measurements. The teleoperated examinations had a mean examination time of 26.4 min and were 1.9 times longer compared to the reference (p = 0.001).
This feasibility study of teleoperated echocardiography shows promising results for the presented system. Clinically satisfactory imaging, particularly measurements of dimension and velocities, requires further development of the system.
Quantitative resistance mediated by multiple genetic factors has been shown to increase the potential for durability of major resistance genes. This was demonstrated in the Leptosphaeria ...maculans/Brassica napus pathosystem in a 5year recurrent selection field experiment on lines harboring the qualitative resistance gene Rlm6 combined or not with quantitative resistance. The quantitative resistance limited the size of the virulent isolate population. In this study we continued this recurrent selection experiment in the same way to examine whether the pathogen population could adapt and render the major gene ineffective in the longer term. The cultivars Eurol, with a susceptible background, and Darmor, with quantitative resistance, were used. We confirmed that the combination of qualitative and quantitative resistance is an effective approach for controlling the pathogen epidemics over time. This combination did not prevent isolates virulent against the major gene from amplifying in the long term but the quantitative resistance significantly delayed for 5years the loss of effectiveness of the qualitative resistance and disease severity was maintained at a low level on the genotype with both types of resistance after the fungus population had adapted to the major gene. We also showed that diversity of AvrLm6 virulence alleles was comparable in isolates recovered after the recurrent selection on lines carrying either the major gene alone or in combination with quantitative resistance: a single repeat-induced point mutation and deletion events were observed in both situations. Breeding varieties which combine qualitative and quantitative resistance can effectively contribute to disease control by increasing the potential for durability of major resistance genes.
•Of all MM methods used during aseptic handling, glove print is the most informative.•The added value of air sampling during aseptic handling is doubtful.•CRR is the best instrument for assessing the ...results of MM inside, or related to, working in LAF/SC.•A CRR < 10% is a realistic limit for MM during aseptic handling in hospital pharmacies.•For predicting process changes a rolling CRR using the last 100 samples is advised, in combination with the accompanying reference value.
Aseptic handling is the procedure to enable sterile products to be made ready to administer using closed systems (EU Resolution CM/Res(2016)2). Microbiological monitoring (MM) and media fills are used for environmental and process control.
In this study, the application of MM methods during aseptic handling inside, or related to working in, a laminar airflow cabinet or safety cabinet in hospital pharmacies is described and evaluated. Results are expressed as colony forming units (cfu) and Contamination Recovery Rate (CRR; the rate at which MM samples contain any level of contamination -USP -). For trend analysis, a rolling CRR is developed (a rolling CRR calculates a CRR using a predetermined number of most recent samples).
Of all MM methods, glove print is the most informative. The added value of air sampling is doubtful. Because of microbiological as well as statistical considerations, the use of CRR for assessing MM results is advised. Glove prints, in general, give the highest CRR. A CRR < 10% is a realistic limit for MM during aseptic handling in hospital pharmacies. A rolling CRR, calculated using the last 100 samples, is a good compromise between reliability of the CRR value and timely prediction of process changes.
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The most common and effective way to control phoma stem canker (blackleg) caused by Leptosphaeria maculans in oilseed rape (Brassica napus) is through the breeding of resistant cultivars. Race ...specific major genes that mediate resistance from the seedling stage have been identified in B. napus or have been introgressed from related species. Many race specific major genes have been described and some of them are probably identical in B. napus (allotetraploid AACC) and the parental species B. rapa (diploid AA). More work is needed using a set of well-characterised isolates to determine the number of different major resistance genes available. In some B. napus cultivars, there is resistance which is polygenic (mediated by Quantitative Trait Loci) and postulated to be race non-specific. Many of these major genes and Quantitative Trait Loci for resistance to L. maculans have been located on B. napus genetic maps. Genes involved in race specific and polygenic resistance are generally distinct.
ObjectivesTo describe the application of the model described in part A and part B of this series of articles for risk assessment (RA) and risk control (RC) of non-sterility during aseptic handling. ...The model was applied in nine hospital pharmacies.MethodsThe starting point was an audit of each hospital pharmacy. The determined risk reduction and remaining risks were entered into a risk assessment model. The corresponding risk prioritisation numbers (RPNs) for each source of risk were calculated and these values were summed up to a cumulative RPN. Subsequently, all hospital pharmacies started an improvement programme, using the risk assessment as input. Results of aseptic process simulation (APS) and microbiological monitoring (MM) were also collected. The participants were informed about their progress of risk reduction and results of APS and MM during the study period. At the end of the study (about 4 years after the start), a final assessment was executed by using a checklist with risk reducing measures for each source of risk. Additional risk reduction and remaining risks were put in an RA and RC template and corresponding RPN values and a new cumulative RPN were determined.ResultsAt the start of the study differences in cumulative RPN values were relatively small (from 630 to 825). At the end they were relatively great (from 230 to 725), which illustrates a different sense of urgency for reducing the risk of non-sterility. Of all the risk reducing measures, a yearly audit of all operators had the greatest impact on reducing the risk of non-sterility. Except for glove prints, there was no correlation between process improvement (lower cumulative RPN) and results of microbiological controls.ConclusionA systematic and science-based reduction of the risks of non-sterility can be done by using a checklist with risk reducing measures and an RA & RC template. Prospectively, the relevance of each risk reducing measure can be demonstrated by RPN calculations. Microbiological controls are an important part of the overall assurance of product quality. However, the results are less useful for assessing the risk of non-sterility.
Three avirulence genes, AvrLm1, AvrLm6, and AvrLm4-7, were recently identified in Leptosphaeria maculans and found to be localized as solo genes within large noncoding, heterochromatin-like regions ...mainly composed of retrotransposons, truncated and degenerated by repeat-induced point mutation (RIP). The Rlm6 resistance gene has been overcome within 3 years in outdoor experiments in France and, here, we investigate the molecular basis of evolution toward virulence at the AvrLm6 locus. A region of 235 kb was sequenced in a virulent isolate and showed the deletion of AvrLm6 and three divergent mosaics of retrotransposons. AvrLm6 was found to be absent from 66% of 70 virulent isolates, with multiple events of deletion. The sequencing of virulent alleles in 24 isolates revealed a few cases of point mutations that had created stop codons in the sequence. The most frequent mutation events, however, were RIP, leading to the modification of 4 to 9% of the bases compared with the avirulent allele and generating 2 to 4 stop codons. Thus, RIP is described for the first time as an efficient mechanism leading to virulence and the multiple patterns of mutation observed suggest that multiple RIP events could occur independently in a single field population during 1 year.
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