Mixed reality holograms for heart surgery planning: first user experience in congenital heart disease.

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSION: 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.

Quantitative resistance affects the speed of frequency increase but not the diversity of the virulence alleles overcoming a major resistance gene to Leptosphaeria maculans in oilseed rape.

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.

New biomarkers in an acute model of live Escherichia coli-induced sepsis in pigs.

We developed a live Escherichia coli model of acute sepsis in pigs with emphasize on biomarkers reflecting the early inflammatory response of sepsis. Healthy pigs, 25-35 kg, were challenged intravenously (IV) (n = 12) or intrapulmonary (n = 6) with live E. coli and observed for 3 and 5 h respectively. Control pigs received culture medium (n = 6 + 3). Haemodynamic parameters and a broad panel of inflammatory mediators were measured. The dose of bacteria was carefully titrated to obtain a condition resembling the early phase of human septic shock. The IV group displayed a pro-inflammatory response [significant increase in tumour necrosis factor-alpha, interleukin (IL)-6 and IL-8] and an early anti-inflammatory response (significant increase in IL-10). For the first time, we demonstrate a significant increase in IL-12 and matrix metalloproteinase-9 (MMP) early in pig sepsis. Coagulation was activated (significant increase in thrombin-antithrombin complexes) and there was a significant decrease in the serum proteins suggesting capillary leakage. Haemodynamic parameters reflected a septic condition with significant decrease in systemic blood pressure, increases in heart rate, pulmonary artery pressure and base deficit. None of these changes was observed in the control group. Interleukin-1beta and vascular endothelial growth factor increased in both groups. Nitric oxide measurements suggested an initial pulmonary vascular endothelial inflammatory response. The intrapulmonary group, which did not resemble septic condition, showed a substantial increase in MMP-9. In this porcine model of sepsis, IL-12 and MMP-9 were detected for the first time. These biomarkers may have an impact in the understanding and future treatment of sepsis.

Stabilization of Resistance to Leptosphaeria maculans in Brassica napus-B. juncea Recombinant Lines and Its Introgression into Spring-Type Brassica napus.

The value of Katanning Early Maturing (KEM) breeding lines from Western Australia, derived from Brassica napus × B. juncea crosses, was assessed as a source of germplasm for resistance to blackleg disease (caused by Leptosphaeria maculans) in spring-type oilseed rape cultivars. The stability of blackleg resistance in these KEM lines was related to key cytological characteristics to determine why there are poor levels of introgression of this resistance into progeny. Promising recombinant KEM lines were crossed with the spring-type B. napus cv. Dunkeld, which has useful polygenic resistance to blackleg, and screened for resistance. The lines were analyzed cytologically for pairing of bivalents in each generation to aid in the selection of stable recombinant lines. KEM recombinant lines showing regular meiotic behavior and a high level of blackleg resistance were obtained for the first time. We also showed that the stable introgression of the B. juncea resistance from the KEM lines into a 'Dunkeld' background was possible. Inoculation of selfing and backcross populations with isolates of L. maculans having different AvrLm genes indicated that the B. juncea resistance gene, Rlm6, had been introgressed into a B. napus spring-type cultivar carrying polygenic resistance. The combination of both resistances would enhance the overall effectiveness of resistance against L. maculans. This is clearly needed in Australia and France where cultivars relying upon single dominant gene-based resistance for their effectiveness have proved not durable.

Detection, introgression and localization of genes conferring specific resistance to Leptosphaeria maculans from Brassica rapa into B. napus.

Blackleg (stem canker) caused by the fungus Leptosphaeria maculans is one of the most damaging diseases of oilseed rape (Brassica napus). Crop relatives represent a valuable source of "new" resistance genes that could be used to diversify cultivar resistance. B. rapa, one of the progenitors of B. napus, is a potential source of new resistance genes. However, most of the accessions are heterozygous so it is impossible to directly detect the plant genes conferring specific resistance due to the complex patterns of avirulence genes in L. maculans isolates. We developed a strategy to simultaneously characterize and introgress resistance genes from B. rapa, by homologous recombination, into B. napus. One B. rapa plant resistant to one L. maculans isolate was used to produce B. rapa backcross progeny and a resynthesized B. napus plant from which a population of doubled haploid lines was derived after crossing with natural B. napus. We then used molecular analyses and resistance tests on these populations to identify and map the resistance genes and to characterize their introgression from B. rapa into B. napus. Three specific genes conferring resistance to L. maculans (Rlm1, Rlm2 and Rlm7) were identified in B. rapa. Comparisons of genetic maps showed that two of these genes were located on the R7 linkage group, in a region homologous to the region on linkage group N7 in B. napus, where these genes have been reported previously. The results of our study offer new perspectives for gene introgression and cloning in Brassicas.

Cyclodextrin inclusion complexes of the central analgesic drug nefopam.

Inclusion complexes of nefopam base (NEF) with various beta-cyclodextrins (betaCDs) were investigated. All tested betaCDs increased the apparent solubility of NEF according to a Higuchi AL type plot (except betaCD: AN type plot), which indicates the formation of 1:1 stoichiometry inclusion complexes. 1H-NMR and 13C-NMR experiments showed that complexation by CDs allowed an easy separation of the R and S enantiomers. Based on spectral data obtained from the two-dimensional rotating frame nuclear Overhauser effect spectroscopy (2D-ROESY), a reasonable geometry for the complexes could be proposed implicating the insertion of the benzoxazocine ring into the wide end of the torus cavity.

Microsporidians in penaeid shrimp along the west coast of Madagascar.

Three species of penaeid shrimp, Fenneropenaeus indicus, Penaeus monodon and P. semisulcatus, found in trawler catches off the west coast of Madagascar were infected with microsporidian parasites. The infections were evident as muscular lesions with a cottony appearance when abundant. Spore size (2.6 x 1.6 microm) and morphology (ovoid) for the parasites infecting both F. indicus and P. semisulcatus were not significantly different, suggesting that they might be the same microsporidian species. Spore size (1.4 x 1.1 microm) and morphology (sub-globose to ovoid) in P. monodon infections were significantly different from those in the other 2 shrimp species, suggesting that it was a different parasite. The presence of microsporidians in this biogeographical zone means that there is a potential risk of infections of cultured shrimp in farms situated in the vicinity. This must be assessed by increasing current knowledge of the parasites.

A Cluster of Major Specific Resistance Genes to Leptosphaeria maculans in Brassica napus.

ABSTRACT Two types of genetic resistance to Leptosphaeria maculans usually are distinguished in Brassica napus: qualitative, total resistance expressed at the seedling stage and quantitative, partial resistance expressed at the adult plant stage. The latter is under the control of many genetic factors that have been mapped through quantitative trait loci (QTL) studies using 'Darmor' resistance. The former usually is ascribed to race-specific resistance controlled by single resistance to L. maculans (Rlm) genes. Three B. napus-originating specific Rlm genes (Rlm1, Rlm2, and Rlm4) previously were characterized. Here, we report on the genetic identification of two novel resistance genes, Rlm3 and Rlm7, corresponding to the avirulence genes AvrLm3 and AvrLm7. The identification of a novel L. maculans- B. napus specific interaction allowed the detection of another putative new specific resistance gene, Rlm9. The resistance genes were mapped in two genomic regions on LG10 and LG16 linkage groups. A cluster of five resistance genes (Rlm1, Rlm3, Rlm4, Rlm7, and Rlm9) was strongly suggested on LG10. The relation between all these specific resistance genes and their potential role in adult-plant field resistance is discussed. These two Rlm-carrying regions do not correspond to major QTL for Darmor quantitative resistance.

A Field Method for Evaluating the Potential Durability of New Resistance Sources: Application to the Leptosphaeria maculans-Brassica napus Pathosystem.

ABSTRACT To increase the longevity of new resistance genes by avoiding a rapid change in pathogen populations, we established a new field method to determine, before the release of a resistant cultivar, whether and how rapidly the pathogen population is capable of responding to the selective pressure we impose. This method was applied to the Leptosphaeria maculans-Brassica napus pathosystem. The potential durability of two new major resistance genes introgressed into B. napus from the Brassica B genome was tested separately for each gene under field conditions for 4 years. Successive inoculations with residues of the resistant lines mixed with susceptible contaminated plant material recovered at harvest the previous year were performed in autumn. The Jlm1 resistance gene originating from B. juncea conferred complete resistance on the B. napus-B. juncea recombinant lines MX and MXS to inoculation of the cotyledons with a large diversity of L. maculans isolates. It also gave a high level of stem canker resistance in the field against natural populations of the pathogen. A similar level of resistance was obtained in the B. napus-B. nigra addition line LA4+, containing B. nigra chromosome 4 in a B. napus background. In the second year of the field experiment (i.e., the first in which residues from the resistant lines were included in the inoculation material), both MX and LA4+ maintained a high level of resistance. In the third and fourth years of the field experiment, the resistance of MX and MXS exposed to inoculum produced from their own residues broke down, but against fungal populations from susceptible B. napus or resistant B. nigra material remained effective. In contrast, LA4+ remained highly resistant to all sources of inoculum for the 4-year experiment.

Cytological Investigation of Resistance to Leptosphaeria maculans Conferred to Brassica napus by Introgressions Originating from B. juncea or B. nigra B Genome.

ABSTRACT Introgressions into Brassica napus from the B genome, either the B. nigra chromosome B4 or the B. juncea fragment carrying the Jlm1 gene, have given rise to the B. napus-B. nigra addition line (LA4+) and the B. napus-B. juncea recombinant line (MXS), respectively. The resistance of these two lines to Leptosphaeria maculans is characterized by a hypersensitive reaction (HR) on both the cotyledons and leaves, while the collar displays a high degree of resistance. Responses induced in cotyledons of the two lines by L. maculans inoculation were investigated with emphasis on cytological events underlying the HR and on host defense reactions. Features of host cell changes including condensation and lobing of nuclei, fragmentation of chromatin, disruption of the nuclear membranes, and plasma membrane withdrawal were reminiscent of HR cell death in MXS and LA4+ plants. Restriction of pathogen growth to the infection areas in LA4+ was correlated to reinforcement of cell wall barriers, including wall apposition, papillae, and vessel plugging. In MXS, the lower expression of resistance was associated with a delay in plant responses. These results indicate that mechanisms underlying the HR in the B. napus recombinant and addition lines are differently controlled according to the introgressed genes.

Pathogenicity of Leptosphaeria maculans Isolates on a Brassica napus-B. juncea Recombinant Line.

ABSTRACT The Brassica napus-B. juncea recombinant line (MX), resistant to Leptosphaeria maculans, was produced by interspecific crosses and bears one gene (Jlm1) from the B. juncea B genome. We investigated whether this new resistance was race specific by characterizing protection against a large sample of L. maculans isolates. The pathogenicity of 119 isolates of L. maculans comprising 105 A-group isolates and 14 B-group isolates was studied at the cotyledon stage under controlled conditions using the MX line, the susceptible B. napus cultivar Westar, and the resistant B. juncea cultivar Picra. All but one of the isolates were pathogenic on 'Westar'. Only 3 of the 105 A-group isolates caused very mild symptoms on 'Picra'. Two of these strains were isolated from the MX line and the other from Sinapis arvensis. The other 102 strains caused hypersensitive-type responses. Most B-group isolates were pathogenic on 'Picra'. There were differences in pathogenicity among A-group isolates tested on the MX line, whereas all B-group isolates were pathogenic on this line. A-group isolates obtained from the MX line were more frequently pathogenic on the MX line than those obtained from B. napus cultivars. One isolate from S. arvensis infected the MX line. These results suggest that the resistance of the MX line is unlikely to be durable. Thus, the new resistance gene Jlm1 should probably be used in association with other sources of resistance, in plant breeding schemes, to prevent the breakdown of this resistance.

Risk factors for cholera infection in the initial phase of an epidemic in Guinea-Bissau: protection by lime juice.

Previous studies of cholera transmission have been conducted in the middle or at the end of an epidemic. Since modes of transmission could be different in different phases of an epidemic, we initiated a case-referent study immediately after the first cases had been hospitalized in a recent cholera epidemic in Guinea-Bissau in West Africa in October 1994. The cases investigated were consecutive adult patients resident in the capital of Bissau who were admitted the the National Hospital during the first two weeks of the epidemic. Referents were matched for district, gender, and age. The study showed a protective effect of using limes in the main meal (odds ratio [OR] = 0.2, 95% confidence interval [CI] = 0.1-0.3) and having soap in the house (OR = 0.3, 95% CI = 0.1-0.8). Not eating with the fingers and using water from a public standpipe were also protective. No specific source or mode of transmission was identified. Thus, cholera control programs in Africa may have to emphasize general hygienic conditions and the use of acidifiers in food preparation.

Optimization of microencapsulation of acrylic adhesives.

The preparation of microcapsules of an acrylic adhesive in a solvent medium with reticulated walls of melamine-formaldehyde was studied. In order to obtain the best experimental conditions for this process, the methodology of factorial design was used. It was found that, among the 11 tested parameters, four had an important effect on the microencapsulation: amount of wall polymer, amount and nature of the copolymer, GANTREZ, and amount of adhesive in the core. The process was optimized using a surface response methodology. A layer of microcapsules deposited on paper gave, after manual breakage, very good adhesive properties.

Requirement of phosphatidylcholine for normal progression through the cell cycle in C3H/10T1/2 fibroblasts.

We have investigated the possible requirement of phosphatidylcholine for normal progression through the cell cycle of C3H/10T1/2 fibroblasts. Incubation of the cells in a medium with 0.5% serum synchronized the cells in the G0 stage of the cell cycle. Supplementation of the cells with 10% dialyzed and delipidated serum +/- choline resulted in normal cell division and growth for cells with choline, whereas cell division was markedly impaired in the absence of choline. Flow cytofluorometry analysis indicated that after 4 days in the absence of choline, 85% of the fibroblasts were in the G1 phase. Addition of choline resulted in synchronous synthesis of DNA with a peak occurring after 14 h. Incubation of cells with 0.5% serum had no effect on phosphatidylcholine (PC) levels in cells supplemented with 28 microM choline, but the concentration of PC was reduced from 32 to 20 nmol/10(6) cells after 1 day of incubation in the absence of choline. Supplementation with dialyzed serum, but not dialyzed and delipidated serum, allowed choline-deficient cells to replicate normally. This was attributed to the presence of lysophosphatidylcholine in dialyzed serum as this lipid, but not other lipids (e.g., phosphatidylcholine or mitogenic lipids) was able to replace the choline requirement. The choline-deficient effect was not complete; some DNA synthesis occurred in the absence of choline in the medium, and approximately 30% of the cells completed mitosis in 35 h compared to 100% in the presence of choline. The data suggest that phosphatidylcholine is required for normal progression of the cell cycle beyond the G1 phase and is unrelated to the induction of G0 to G1 transition. Choline deficiency should be a useful method for synchronizing cells in the G1 phase.

Influence of experimental parameters on the microencapsulation of a photopolymerizable phase.

Conditions of microencapsulation by in situ polycondensation, using melamine-formaldehyde as wall material, are influenced by the chemical nature of the core to encapsulate. In our study concerning the encapsulation of a photopolymerizable phase containing an electrically charged compound, it was necessary to modify the experimental process to obtain capsules of good quality. We used the factorial design method of screening by utilization of an asymmetric matrix, according to the collapsing principle of Addleman. The advantage of this method is that it allows determination of the simultaneous influences of the 11 experimental parameters involved in this preparation. The calculation method can be applied to more than two levels for some of the factors. The continuously varying parameters were altered between two extreme levels, chosen to allow encapsulation. For discontinuous factors, such as the molecular weight of the modifying system or nature of the aminoplast, we used the commercially available compounds, respectively three and four kinds. The results of the obtained capsules were determined by comparing microphotographic pictures. With 16 experiments we found four more factors influencing quality of capsules. We also determined the most favourable levels for the other seven parameters. The results allowed us to find optimal conditions in the experimental field. We obtained capsules of a satisfactory quality for this purpose, using only minimum experimentation.

Main parameters involved in microencapsulation by in situ polycondensation.

The influences of 11 factors are studied. Molecular weight of the emulsifier, amount of wall material and amount of core material were found to be the most influential factors.

Improvement of a microencapsulation with aqueous core by factorial design.

Preparation of microcapsules with aqueous core and polyamide walls is influenced by several factors. We improved the stability of walls and size of capsules by simultaneous variation of four factors: total ratio of polymer, ratio of amines to acid chlorides, concentration of surfactant and speed of stirring. Use of factorial design minimizes the number of experiments and permits us to know the influence of these factors and of their interactions. By increasing the ratio of amines to acid chlorides and with a low concentration of total polymer, we obtained more stable capsules. Surfactant had a negative effect on the hardness of the polymer.

[Deaths caused by antidepressive agents and neuroleptics. Risk groups illustrated by a forensic material]. / Dødsfall forårsaket av antidepressiva og neuroleptika. Risikogrupper belyst ved et rettsmedisinsk materiale.

At the Institute of Forensic Medicine, University of Oslo, legal autopsy was performed on 153 persons who died from poisoning by neuroleptics and/or antidepressants from 1986 to 1989. In one third of the cases, only neuroleptics were found at autopsy, and in little less than half of these cases the post mortem blood concentrations were considered rather low in relation to the fatal outcome. A larger proportion of alcohol abusers were found in the group with low post mortem concentrations of neuroleptics than in the rest of the material. This group contained mainly men and was further characterized by a high proportion of unintentional deaths. In the light of these facts the authors speculate whether neuroleptics represent increased risk of sudden death among alcohol abusers. The deaths due to an overdose of antidepressants were mostly suicides, and involved high post mortem blood concentrations of the drugs.