Comparison of manual and semi-automatic registration in augmented reality image-guided liver surgery: a clinical feasibility study.

BACKGROUND: The laparoscopic approach to liver resection may reduce morbidity and hospital stay. However, uptake has been slow due to concerns about patient safety and oncological radicality. Image guidance systems may improve patient safety by enabling 3D visualisation of critical intra- and extrahepatic structures. Current systems suffer from non-intuitive visualisation and a complicated setup process. A novel image guidance system (SmartLiver), offering augmented reality visualisation and semi-automatic registration has been developed to address these issues. A clinical feasibility study evaluated the performance and usability of SmartLiver with either manual or semi-automatic registration. METHODS: Intraoperative image guidance data were recorded and analysed in patients undergoing laparoscopic liver resection or cancer staging. Stereoscopic surface reconstruction and iterative closest point matching facilitated semi-automatic registration. The primary endpoint was defined as successful registration as determined by the operating surgeon. Secondary endpoints were system usability as assessed by a surgeon questionnaire and comparison of manual vs. semi-automatic registration accuracy. Since SmartLiver is still in development no attempt was made to evaluate its impact on perioperative outcomes. RESULTS: The primary endpoint was achieved in 16 out of 18 patients. Initially semi-automatic registration failed because the IGS could not distinguish the liver surface from surrounding structures. Implementation of a deep learning algorithm enabled the IGS to overcome this issue and facilitate semi-automatic registration. Mean registration accuracy was 10.9 ± 4.2 mm (manual) vs. 13.9 ± 4.4 mm (semi-automatic) (Mean difference - 3 mm; p = 0.158). Surgeon feedback was positive about IGS handling and improved intraoperative orientation but also highlighted the need for a simpler setup process and better integration with laparoscopic ultrasound. CONCLUSION: The technical feasibility of using SmartLiver intraoperatively has been demonstrated. With further improvements semi-automatic registration may enhance user friendliness and workflow of SmartLiver. Manual and semi-automatic registration accuracy were comparable but evaluation on a larger patient cohort is required to confirm these findings.

Impact of total variation minimization in volume rendering visualization of breast tomosynthesis data.

BACKGROUND AND OBJECTIVE: Total Variation (TV) minimization algorithms have achieved great attention due to the virtue of decreasing noise while preserving edges. The purpose of this work is to implement and evaluate two TV minimization methods in 3D. Their performance is analyzed through 3D visualization of digital breast tomosynthesis (DBT) data with volume rendering. METHODS: Both filters were studied with real phantom and one clinical DBT data. One algorithm was applied sequentially to all slices and the other was applied to the entire volume at once. The suitable Lagrange multiplier used in each filter equation was studied to reach the minimum 3D TV and the maximum contrast-to-noise ratio (CNR). Imaging blur was measured at 0° and 90° using two disks with different diameters (0.5 mm and 5.0 mm) and equal thickness. The quality of unfiltered and filtered data was analyzed with volume rendering at 0° and 90°. RESULTS: For phantom data, with the sequential filter, a decrease of 25% in 3D TV value and an increase of 19% and 30% in CNR at 0° and 90°, respectively, were observed. When the filter is applied directly in 3D, TV value was reduced by 35% and an increase of 36% was achieved both for CNR at 0° and 90°. For the smaller disk, variations of 0% in width at half maximum (FWHM) at 0° and a decrease of about 2.5% for FWHM at 90° were observed for both filters. For the larger disk, there was a 2.5% increase in FWHM at 0° for both filters and a decrease of 6.28% and 1.69% in FWHM at 90° with the sequential filter and the 3D filter, respectively. When applied to clinical data, the performance of each filter was consistent with that obtained with the phantom. CONCLUSIONS: Data analysis confirmed the relevance of these methods in improving quality of DBT images. Additionally, this type of 3D visualization showed that it may play an important complementary role in DBT imaging. It allows to visualize all DBT data at once and to analyze properly filters applied to all the three dimensions. Concise Abstract Total Variation (TV) minimization algorithms are one compressed sensing technique that has achieved great attention due to the virtue of decrease noise while preserve edges transitions. The purpose of this work is to solve the same TV minimization problem in DBT data, by studying two 3D filters. The obtained results were analyzed at 0° and 90° with a 3D visualization through volume rendering. The filters differ in their application. One considers a slice-by-slice optimization, sequentially traversing all slices of the data. The other considers the intensity values of adjacent slices to make this optimization on each voxel. The performance of each filter was also tested with a clinical case. The results obtained were very encouraging with a significantly increased contrast to noise ratio at 0° and 90° and a small reduction in blur at 90° (slight reduction of the out-of-plane artifact).

Detection and modelling of contacts in explicit finite-element simulation of soft tissue biomechanics.

PURPOSE: Realistic modelling of soft tissue biomechanics and mechanical interactions between tissues is an important part of biomechanically-informed surgical image-guidance and surgical simulation. This submission details a contact-modelling pipeline suitable for implementation in explicit matrix-free FEM solvers. While these FEM algorithms have been shown to be very suitable for simulation of soft tissue biomechanics and successfully used in a number of image-guidance systems, contact modelling specifically for these solvers is rarely addressed, partly because the typically large number of time steps required with this class of FEM solvers has led to a perception of them being a poor choice for simulations requiring complex contact modelling. METHODS: The presented algorithm is capable of handling most scenarios typically encountered in image-guidance. The contact forces are computed with an evolution of the Lagrange-multiplier method first used by Taylor and Flanagan in PRONTO 3D extended with spatio-temporal smoothing heuristics for improved stability and edge-edge collision handling, and a new friction model. For contact search, a bounding-volume hierarchy (BVH) is employed, which is capable of identifying self-collisions by means of the surface-normal bounding cone of Volino and Magnenat-Thalmann, in turn computed with a novel formula. The BVH is further optimised for the small time steps by reducing the number of bounding-volume refittings between iterations through identification of regions with mostly rigid motion and negligible deformation. Further optimisation is achieved by integrating the self-collision criterion in the BVH creation and updating algorithms. RESULTS: The effectiveness of the algorithm is demonstrated on a number of artificial test cases and meshes derived from medical image data. It is shown that the proposed algorithm reduces the cost of BVH refitting to the point where it becomes a negligible part of the overall computation time of the simulation. It is also shown that the proposed surface-normal cone computation formula leads to about 40 % fewer BVH subtrees that must be checked for self-collisions compared with the widely used method of Provot. The proposed contact-force formulation and friction model are evaluated on artificial test cases that allow for a comparison with a ground truth. The quality of the proposed contact forces is assessed in terms of trajectories and energy conservation; a [Formula: see text]0.4 % drop off in total energy and highly plausible trajectories are found in the experiments. The friction model is evaluated through a benchmark problem with an analytical solution and a maximum displacement error of 8.2 %, and excellent agreement in terms of the stick/slip boundary is found. Finally, we show with realistic image-guidance examples that the entire contact-modelling pipeline can be executed within a timeframe that is of the same order of magnitude as that required for standard FEM computations.

Validating indicators of sheep welfare through a consensus of expert opinion.

A consensus of expert opinion was used to provide both face and consensual validity to a list of potential indicators of sheep welfare. This approach was used as a first step in the identification of valid welfare indicators for sheep. The consensus methodology of the National Institute of Health, using pre-meeting consultation and focus group discussions, was used to ascertain the consensus opinion of a panel of sheep welfare experts. The Farm Animal Welfare Council's five freedoms were used as a framework to organise a list of current on-farm welfare issues for sheep. The five freedoms were also the welfare criterion used to identify potential on-farm welfare indicators for sheep. As a result, experts identified 193 welfare issues for sheep and lambs managed on farms across England and Wales. Subsequently, a combination of animal- (n = 26), resource- (n = 13) and management- (n = 22) based indicators was suggested for (i) adult rams, (ii) adult ewes (male and female sheep, over 1 year old), (iii) growing lambs (male and female sheep, over 6 weeks to 1 year old) and (iv) young lambs (male and female lambs, 6 weeks old and under). The results from this study could therefore be used to inform the further development of valid methods of assessing the on-farm welfare of sheep.

The turkey, compared to the chicken, fails to mount an effective early immune response to Histomonas meleagridis in the gut.

Histomonosis is a disease of poultry caused by Histomonas meleagridis. Chickens usually recover while the mortality rate in turkeys is high. The immunological response of both species towards H. meleagridis was investigated. Parasites migrated in greater numbers to the turkey liver compared with that of chicken. Chicken mounted an effective caecal innate response, with increased expression of IL-1beta, CXCLi2 and IL-6 mRNA, resulting in control of parasite numbers. The turkey failed to mount such an effective innate response in the caecal tonsil, allowing greater numbers to migrate to the liver, where a sustained, uncontrolled immune response was mounted, evidenced by the upregulation of mRNA for IL-1beta, CXCLi2, IFN-gamma, IL-13, IL-4 and IL-10. Expression levels of mRNA of the chicken and turkey beta-defensin AvBD2 suggest that this response was not limited to the cytokines. There was an influx of CD4+, CD8alpha+, CD28+ and CD44+ cells into the livers of both species, coinciding with parasite movement. These influxes were more pronounced in the turkey, correlating with a decrease in numbers of the same cells in the spleen, which was not observed in the chicken. Antibody levels in the chicken increased more than those in the turkey, supporting evidence of an adaptive response.

Crystal structure of a nucleosome core particle containing the variant histone H2A.Z.

Activation of transcription within chromatin has been correlated with the incorporation of the essential histone variant H2A.Z into nucleosomes. H2A.Z and other histone variants may establish structurally distinct chromosomal domains; however, the molecular mechanism by which they function is largely unknown. Here we report the 2.6 A crystal structure of a nucleosome core particle containing the histone variant H2A.Z. The overall structure is similar to that of the previously reported 2.8 A nucleosome structure containing major histone proteins. However, distinct localized changes result in the subtle destabilization of the interaction between the (H2A.Z-H2B) dimer and the (H3-H4)(2) tetramer. Moreover, H2A.Z nucleosomes have an altered surface that includes a metal ion. This altered surface may lead to changes in higher order structure, and/or could result in the association of specific nuclear proteins with H2A.Z. Finally, incorporation of H2A.Z and H2A within the same nucleosome is unlikely, due to significant changes in the interface between the two H2A.Z-H2B dimers.

The specificity of antibody responses in cattle naturally exposed to Fasciola hepatica.

Fasciola hepatica causes significant morbidity and mortality in dairy cattle in the Andean region of Cajamarca, Peru, where prevalence of infection of up to 78% has been reported. ELISA and Western blot analyses were used to characterise antibody responses in dairy cattle to adult F. hepatica to excretory-secretory (E/S), somatic (SO) and surface (SU) antigens. Three groups of dairy cattle - calves, heifers and adult cows - naturally exposed to F. hepatica in this region, were monitored every 2 months over a 2-year period. Calves, heifers and adult cows all had antibodies which recognised a 28kDa protein in the SO preparation, whereas only adult cows had antibodies that recognised a 28kDa protein in E/S products. All three groups of cattle responded to a 60-66kDa group of proteins in E/S and SU preparations and a 17kDa antigen in SO products was recognised by antibodies from cows and heifers but not calves. The total antibody response to E/S antigens measured by ELISA, increased over time in calves and remained constantly high over the 2-year period in all three groups of cattle. Slight fluctuations in the antibody response occurred in the group of heifers and cows coinciding with seasonal changes in the level of challenge.

Distinct importin recognition properties of histones and chromatin assembly factors.

Synthesis of the protein components of nuclear chromatin occurs in the cytoplasm, necessitating specific import into the nucleus. Here, we report the binding affinities of the nuclear localisation sequence (NLS)-binding importin subunits for a range of histones and chromatin assembly factors. The results suggest that import of histones to the nucleus may be mediated predominantly by importin beta1, whereas the import of the other components probably relies on the conventional alpha/beta1 import pathway. Differences in recognition by importin beta1 were observed between histone H2A and the variant H2AZ, as well as between histone H3/4 with or without acetylation. The results imply that different histone variants may possess distinct nuclear import properties, with acetylation possibly playing an inhibitory role through NLS masking.

Regions of variant histone His2AvD required for Drosophila development.

One way in which a distinct chromosomal domain could be established to carry out a specialized function is by the localized incorporation of specific histone variants into nucleosomes. H2AZ, one such variant of the histone protein H2A, is required for the survival of Drosophila melanogaster, Tetrahymena thermophila and mice (R. Faast et al., in preparation). To search for the unique features of Drosophila H2AZ (His2AvD, also referred to as H2AvD) that are required for its essential function, we have performed amino-acid swap experiments in which residues unique to Drosophila His2AvD were replaced with equivalently positioned Drosophila H2A.1 residues. Mutated His2AvD genes encoding modified versions of this histone were transformed into Drosophila and tested for their ability to rescue null-mutant lethality. We show that the unique feature of His2AvD does not reside in its histone fold but in its carboxy-terminal domain. This C-terminal region maps to a short alpha-helix in H2A that is buried deep inside the nucleosome core.

The effect of cyclic temperatures on the growth of Fasciola hepatica and Lymnaea viatrix.

The experiment aimed to measure the effect of constant and variable temperatures on the growth of Lymnaea viatrix snails, on the development of a Peruvian isolate of Fasciola hepatica eggs and on the development of F. hepatica in the snails. This was carried out by cultivating infected and uninfected snails and fluke eggs in artificial, temperature controlled chambers. L. viatrix snails were found to develop at a rate dependent on environmental temperature, but developed at least as well under conditions of varying temperature as at the same mean constant temperature. F. hepatica eggs held at constant or varying temperatures, developed at a rate comparable to other reports. However, eggs developing at varying temperatures appeared to have reduced hatchability. Parasite development within the snails was slow, though within the limits calculated from the literature, and varying temperature did not appear to reduce development compared to constant temperatures.

Strategic control of fasciolosis in the inter-Andean valley of Cajamarca, Peru.

Fasciolosis is recognised as a major problem in dairy cattle in Cajamarca, Peru. The infection has an annual cycle, with the major period of infection from January to March. A control programme, involving two doses of the fasciolicide triclabendazole aimed at reducing the passage of Fasciola hepatica eggs on to the pasture, together with the use of the molluscicide, niclosamide, was evaluated against traditional treatment programmes. The double treatment regimen did not significantly reduce the overall parasite burden, as measured by faecal egg counts, but did control the parasites to a level similar to that achieved by traditional programmes averaging 3-7 treatments per year. The cows' eosinophil counts and serum liver enzyme activities were significantly lower than in animals treated by the traditional programmes. The use of niclosamide in addition to the triclabendazole treatments gave no clear advantage, although there was a significant reduction in the number of intermediate host snails after the application of the molluscicide.

Acute phase toxoplasma abortions in sheep.

Within 13 days of the experimental infection of 15 oestrus-synchronised ewes with 2000 sporulated oocysts of Toxoplasma gondii at 80 to 90 days of gestation 11 had aborted. The infection induced pyrexia and specific antibody in all the ewes. One ewe resorbed its fetus, 11 ewes aborted and three delivered, at full term, live congenitally infected lambs whose pre-colostral serum was antibody-positive. Tissues from the aborted fetuses and placentae from the live lambs were examined for toxoplasma infection by polymerase chain reaction (PCR) amplification of the B1 gene and by mouse inoculation. The live lambs were all shown to be infected by both methods, but there was no evidence of infection in any of the tissues from the acute phase abortions, suggesting that these fatalities occurred before the placenta or the fetus had been invaded by T gondii. Such toxoplasma-induced, acute-phase abortions are likely to be impossible to diagnose from fetal tissues. These results have implications not only for the diagnosis of naturally occurring ovine abortions but also for the understanding of the pathogenesis of toxoplasma-induced abortion.

Diagnosis of toxoplasma abortion in ewes by polymerase chain reaction.

Eighteen oestrus-synchronised ewes were infected experimentally with 1500 sporulated oocysts of Toxoplasma gondii between 80 and 90 days of gestation. The infection induced pyrexia and specific antibody in all the ewes. One ewe resorbed its fetus, five ewes aborted and 12 delivered live, congenitally-infected lambs whose pre-colostral serum was antibody-positive. Tissues from the aborted fetuses and placentae from the live lambs were examined for toxoplasma infection by polymerase chain reaction (PCR) amplification of the B1 gene and by mouse inoculation. Using a simple protocol of tissue preparation without DNA extraction and a nested format, PCR was as sensitive as mouse inoculation. Placental cotyledon gave a higher sensitivity of detection than brain, lung or liver, and 16 of 19 placentae were positive by PCR compared with 13 of 18 by mouse inoculation. In mock-infected tissues, as few as 10 tachyzoites could be detected. The PCR could be applied to tissues unfit for mouse inoculation.

Experimental infection of pregnant ewes with Chlamydia pecorum.

Pregnant ewes were infected in midpregnancy with three isolates of Chlamydia pecorum derived from the feces of healthy lambs from three different farms. Oral infection, alone or together with Fasciola hepatica, did not result in tissue invasion, since all placental and fecal samples were negative for chlamydiae. Intravenous infection resulted in placental infection in 16 of 18 ewes in that chlamydiae were cultured from placentas or vaginal swabs. Two ewes bore dead lambs after a shortened gestation time. The chlamydiae isolated were all C. pecorum. There were no significant differences between the weights of the lambs from the infected groups and those from uninfected control ewes. Most ewes showed no serological evidence of infection by the complement fixation test; therefore, it is unlikely that the enteric subtype of C. pecorum is responsible for the cross-reactions sometimes seen in flocks being tested for C. psittaci infection.

Isolation of faecal chlamydia from sheep in Britain and their characterization by cultural properties.

Faeces samples were taken per rectum from sheep on 26 farms in England and Wales and examined for the presence of chlamydia by culture in McCoy cell monolayers. Thirteen of the farms were known to have had abortion outbreaks associated with Chlamydia psittaci (enzootic abortion) and 13 were free of this infection. The chlamydia isolated were characterized by cultural techniques. Chlamydia were isolated from the faeces of lambs on all 26 farms and the prevalence of infection varied form 5-50% on individual farms. There was no significant difference between the proportion of infected lambs on farms where enzootic abortion was present or absent. Lambs first showed infection when they were 3 months old and the prevalence rate of infection increased up to 9 months old. No chlamydia were isolated from the faeces of 316 adult ewes. The chlamydia were identified as enteric rather than abortion type and thus were C. pecorum rather than C. psittaci.

Epidemiology of lameness in dairy cattle: the influence of cubicles and indoor and outdoor walking surfaces.

A survey of cubicles and indoor and outdoor walking surfaces on 37 farms served by four veterinary practices in Somerset, Cheshire, Wirral and west. Wales was carried out in 1989 to 1991. A study of the space requirements of Friesian/Holstein cows at pasture showed that they required approximately 240 cm x 120 cm lying space and a further 60 cm lunging space for rising. By these standards, 87 per cent of the cubicles were too short and 50 per cent were too wide or too narrow. Over 1500 observations on cows lying down, rising and standing indicated that only 12 per cent of the cubicles permitted real freedom of movement; 91 per cent of top partition rails were judged to be too low and 70 per cent of bottom rails too low or too high. In addition, the kerb was very high in 76 per cent of the cubicles. As a result, 10 per cent of cows appeared moderately or severely restricted when lying down, 33 per cent when rising and 55 per cent when standing. Over 2000 cubicle beds were also studied; 75 per cent had a concrete base and of those, 63 per cent were judged to have too little bedding and 11 per cent next to none. Higher incidences and prevalences of lameness were associated with limited borrowing space (P < 0.01) low bottom rails (P < 0.05), high kerbs (P < 0.05) and inadequate bedding (P < 0.01). Of 3190 walking surfaces, only 25 per cent were classified as satisfactory in the first winter and 34 per cent in the second. In general, surfaces in silage bays were too rough and those in other sites were too smooth. The farms with the smoothest indoor walking surfaces had a significantly higher incidence of lameness (P < 0.01). Of 3335 outdoor walking surfaces only 25 per cent were classified as satisfactory, and 70 per cent were too rough. The incidence of lameness was not significantly related to these findings.

Incidence and prevalence of lameness in dairy cattle.

A survey was made of 37 dairy farms in Wirral, mid-Cheshire, mid-Somerset and Dyfed, Wales, to assess the incidence and prevalence of lameness in the cows between May 1989 and September 1991. The incidence was obtained from records made whenever a cow was examined for lameness or received preventive foot-trimming. The mean annual incidence was 54.6 new cases per 100 cows with a range from 10.7 to 170.1 and the mean values during summer and winter were 22.9 and 31.7, respectively. The prevalence of lameness was measured by regular visits at which locomotion was scored on a scale of 1 to 5, and the prevalence of lameness was calculated for each visit as the proportion of cows with scores of 3 or more. The mean annual prevalence over the whole period was 20.6 per cent with a range from 2.0 to 53.9 per cent for the 37 farms. The mean prevalences during summer and winter were 18.6 and 25.0 per cent, respectively. The prevalence measured at a single visit in midsummer or midwinter was significantly correlated with the mean prevalence over the whole corresponding period and may be useful as an assessment of the extent of lameness in a herd and the efficacy of control measures. There was evidence that training farmers to recognise early cases of lameness and request veterinary treatment resulted in a marked reduction in the duration of cases of lameness.

Epidemiology of lameness in dairy cattle: description and analysis of foot lesions.

Information from 37 dairy farms, in four regions of England and Wales provided data on 8991 lesions and the preventive trimming of 4837 cows' feet. Of the total of 13,828 forms returned, veterinary surgeons treated 32 per cent and farmers or stockmen 46 per cent. Of the 8645 lesions associated with episodes of lameness, lesions in the hindlimbs accounted for 92 per cent, of which 65 per cent were in the outer claw, 20 per cent in the skin and 14 per cent in the inner claw. Sole ulcers (40 per cent) and white line lesions (29 per cent) were the predominant diseases of horn, and digital dermatitis (40 per cent) was the most common disease of the skin. Subjective assessments showed that sandcrack, penetration of the sole by foreign bodies and interdigital necrobacillosis were associated with the most severe cases of lameness. There was a significant seasonal effect in the reporting of lesions.