Development, Validation, and Modelling of Image Guidance Systems for Surgery

Image guidance systems for surgery enable the surgeon to make use of information from various sources during surgery. Such systems have the potential to improve outcomes for patients by allowing the surgeon to easily assimilate prior knowledge from pre-operative clinical scans as well as novel intra-operative imaging techniques. A key challenge is how to filter and process this information to allow it to be presented in an accurate, timely, and intuitive manner. Badly designed or poorly understood image guidance systems risk distracting the surgeon with irrelevant or incorrect information, leading to patient harm. The aim of my research is to develop tools to better quantify the performance of surgical image guidance systems, and measure how the system performance affects patient outcomes. I will present the results of my work developing the “SmartLiver”[1] image guidance system for minimally invasive liver surgery. I will follow this with a proposal for a generalised model of image guidance systems as multi input control systems

The continuous combustion of glycerol in a fluidised bed

It is difficult to burn a liquid fuel inside a fluidised bed. For the first time, liquid glycerol has been burned, when continuously injected into the bottom of an electrically heated bed of alumina particles (sieved to 355 – 425 μm), fluidised by air. The temperature in the bed was held at 700, 800 or 900oC; usually (U/Umf) was 2.5. The bed’s depth was varied, as also were (U/Umf) and the ratio of fuel to air supplied to the bed. Measurements were made of the concentrations of CH4, O2, CO and CO2, and also of the temperature, in the freeboard well above the bed. On entering the bed, the liquid glycerol, rapidly formed bubbles of vapour, which quickly decomposed thermally, yielding mostly CO and H2. These gases then mixed with the other gases in the bed. It appears that the diffusive H2 mainly burns between the fluidised particles. With the bed at 700 – 900oC, no CO was detected far downstream of the bed, provided the equivalence ratio, θ, was below 0.7, i.e. with more than 43 % excess air. Under these fuel-lean conditions, all the carbon in the glycerol was oxidised to CO2. However, in a more fuel-rich situation, with θ > 0.7, CO was detected well above the bed, particularly with a deeper bed, at a lower temperature and operating more fuel-rich. Thus, with the bed at 900oC, CO was mostly oxidised inside the bed, but occasionally some CO burned on top of the bed. When a fuel-rich bed was below 850oC, not all the CO burned in the bed. Achieving complete combustion inside a fluidised bed is partly a problem of mixing the products of glycerol’s thermal decomposition with the fluidising air, which on entry exists mainly in bubbles. Consequently, increasing (U/Umf) promoted both mixing and combustion in a bed. In addition, in-bed combustion requires the bed to be sufficiently deep, hotter than 850oC and θ to be less than a critical value. The effects of other variables are discussed

The combustion of solid paraffin wax and of liquid glycerol in a fluidised bed

Two fuels were burned in electrically heated beds of alumina sand, fluidised by air. The fuels were: (i) paraffin wax, which is a solid containing 100% volatile matter and (ii) glycerol, a liquid, whose potential as a fuel needs assessing. The bubbling fluidised beds were held in the range 400–900 °C. Pieces of paraffin wax burned like a plastic, so when fed on top of a bed, the wax floated and generated clouds of soot. Soon, it then sank into the bed. When the sand was below ~800 °C, combustion occurred noisily in exploding bubbles leaving the bed. In beds hotter than ~800 °C, combustion proceeded in bubbles fairly low in the bed and was controlled by the mixing of hydrocarbon vapours (from the wax) with the fluidising air. If wax were fed half way up a bed, bubbles of hydrocarbon vapours were quickly produced; they ascended and mixed with the fluidising air. In a bed below 800 °C, combustion mainly occurred noisily in bubbles just after leaving the bed, but in a hotter bed, there was quieter burning in smaller bubbles, before they reached the top of the bed. Glycerol behaved similarly, when fed into the middle of a bed. Thus bubbles of glycerol vapour were formed; they mixed with air ascending the bed as either bubbles or percolating between particles. Again bubbles exploded noisily at the top of a bed below 800 °C. With the bed above 800 °C, glycerol burned inside smaller bubbles below the bed’s upper surface. No soot was observed when burning glycerol in such a hot bed, yielding CO and CO$_2$ as the only products of combustion. It appears that burning glycerol cleanly in a hot fluidised bed is a feasible proposition

Cross-cultural validation of the Cardiac Depression Scale in Iran

Background. The Cardiac Depression Scale (CDS) is a disease-specific instrument for measuring depression in cardiac patients. This study was designed to validate the CDS in an Iranian population. Methods. Translation and back-translation of the 26-item CDS scale was performed using recommended procedures. The Iranian translation of the CDS (I-CDS) was administered to 261 individuals in Iran, concurrently with the Beck Depression Inventory. The factor structure of the I-CDS was examined using exploratory factor analysis procedures to enable comparison with previous psychometric evaluation ofthe CDS. Receiver operating characteristic curves were used to examine the ability of the I-CDS to discriminate between categories of depression. Results. First-order exploratory factor analysis uncovered two robust factors, consistent with the second-order dimensions originally reported by the developers of this instrument. Cronbach's alpha was .88 for the total 26-item I-CDS, indicating satisfactory internal consistency of the I-CDS. Intercorrelation between the total scores for the I-CDS and BDI was .62 (p < .001). For the I-CDS cut-off of 90, the sensitivity was 85%, and specificity was 61% with a computed area under the curve (AUC) of 0.81 (95% CI, 0.76-0.87). For the I-CDS cut-off of 100, the sensitivity was 81%, and specificity was 63% with a computed AUC of 0.81 (95% CI, 0.76-0.87). Conclusion. This validation study of the Iranian version of theCDSdemonstrated that it is an acceptable, reliable, and valid measure of depression in people with heart disease.Copyright © The British Psychological Society

Molecular heterogeneity in major urinary proteins of Mus musculus subspecies: potential candidates involved in speciation

When hybridisation carries a cost, natural selection is predicted to favour evolution of traits that allow assortative mating (reinforcement). Incipient speciation between the two European house mouse subspecies, Mus musculus domesticus and M.m.musculus, sharing a hybrid zone, provides an opportunity to understand evolution of assortative mating at a molecular level. Mouse urine odours allow subspecific mate discrimination, with assortative preferences evident in the hybrid zone but not in allopatry. Here we assess the potential of MUPs (major urinary proteins) as candidates for signal divergence by comparing MUP expression in urine samples from the Danish hybrid zone border (contact) and from allopatric populations. Mass spectrometric characterisation identified novel MUPs in both subspecies involving mostly new combinations of amino acid changes previously observed in M.m.domesticus. The subspecies expressed distinct MUP signatures, with most MUPs expressed by only one subspecies. Expression of at least eight MUPs showed significant subspecies divergence both in allopatry and contact zone. Another seven MUPs showed divergence in expression between the subspecies only in the contact zone, consistent with divergence by reinforcement. These proteins are candidates for the semiochemical barrier to hybridisation, providing an opportunity to characterise the nature and evolution of a putative species recognition signal

Eta Carinae -- Physics of the Inner Ejecta

Eta Carinae's inner ejecta are dominated observationally by the bright Weigelt blobs and their famously rich spectra of nebular emission and absorption lines. They are dense (n_e ~ 10^7 to 10^8 cm^-3), warm (T_e ~ 6000 to 7000 K) and slow moving (~40 km/s) condensations of mostly neutral (H^0) gas. Located within 1000 AU of the central star, they contain heavily CNO-processed material that was ejected from the star about a century ago. Outside the blobs, the inner ejecta include absorption-line clouds with similar conditions, plus emission-line gas that has generally lower densities and a wider range of speeds (reaching a few hundred km/s) compared to the blobs. The blobs appear to contain a negligible amount of dust and have a nearly dust-free view of the central source, but our view across the inner ejecta is severely affected by uncertain amounts of dust having a patchy distribution in the foreground. Emission lines from the inner ejecta are powered by photoionization and fluorescent processes. The variable nature of this emission, occurring in a 5.54 yr event cycle, requires specific changes to the incident flux that hold important clues to the nature of the central object.Comment: This is Chapter 5 in a book entitled: Eta Carinae and the Supernova Impostors, Kris Davidson and Roberta M. Humphreys, editors Springe

Is Osteogenic Differentiation of Human Nucleus Pulposus Cells a Possibility for Biological Spinal Fusion?

Objective The purpose of this study was to investigate whether a simple, biologically robust method for inducing calcification of degenerate intervertebral discs (IVD) could be developed to provide an alternative treatment for patients requiring spinal fusion. Design Nucleus pulposus (NP) cells isolated from 14 human IVDs were cultured in monolayer and exposed to osteogenic medium, 1,25-dihydroxyvitamin D3 (VitD3), parathyroid hormone (PTH), and bone morphogenic proteins (BMPs) 2/7 to determine if they could become osteogenic. Similarly explant cultures of IVDs from 11 patients were cultured in osteogenic media with and without prior exposure to VitD3 and BMP-2. Osteogenic differentiation was assessed by alkaline phosphatase activity and areas of calcification identified by alizarin red or von Kossa staining. Expression of osteogenic genes during monolayer culture was determined using polymerase chain reaction and explant tissues assessed for BMP inhibitors. Human bone marrow-derived mesenchymal stromal cells (MSCs) were used for comparison. Results Standard osteogenic media was optimum for promoting mineralization by human NP cells in monolayer. Some osteogenic differentiation was observed with 10 nM VitD3, but none following application of PTH or BMPs. Regions of calcification were detected in 2 of the eleven IVD tissue explants, one cultured in osteogenic media and one with the addition of VitD3 and BMP-2. Conclusions Human NP cells can become osteogenic in monolayer and calcification of the extracellular matrix can also occur, although not consistently. Inhibitory factors within either the cells or the extracellular matrix may hinder osteogenesis, indicating that a robust biological fusion at this time requires further optimization

Dietary garlic and hip osteoarthritis: evidence of a protective effect and putative mechanism of action

Background Patterns of food intake and prevalent osteoarthritis of the hand, hip, and knee were studied using the twin design to limit the effect of confounding factors. Compounds found in associated food groups were further studied in vitro. Methods Cross-sectional study conducted in a large population-based volunteer cohort of twins. Food intake was evaluated using the Food Frequency Questionnaire; OA was determined using plain radiographs. Analyses were adjusted for age, BMI and physical activity. Subsequent in vitro studies examined the effects of allium-derived compounds on the expression of matrix-degrading proteases in SW1353 chondrosarcoma cells. Results Data were available, depending on phenotype, for 654-1082 of 1086 female twins (median age 58.9 years; range 46-77). Trends in dietary analysis revealed a specific pattern of dietary intake, that high in fruit and vegetables, showed an inverse association with hip OA (p = 0.022). Consumption of 'non-citrus fruit' (p = 0.015) and 'alliums' (p = 0.029) had the strongest protective effect. Alliums contain diallyl disulphide which was shown to abrogate cytokine-induced matrix metalloproteinase expression. Conclusions Studies of diet are notorious for their confounding by lifestyle effects. While taking account of BMI, the data show an independent effect of a diet high in fruit and vegetables, suggesting it to be protective against radiographic hip OA. Furthermore, diallyl disulphide, a compound found in garlic and other alliums, represses the expression of matrix-degrading proteases in chondrocyte-like cells, providing a potential mechanism of action

Endoglin (CD105) expression in ovarian serous carcinoma effusions is related to chemotherapy status

Endoglin (CD105), a cell surface co-receptor for transforming growth factor-β, is expressed in proliferating endothelial cells, as well as in cancer cells. We studied endoglin expression and its clinical relevance in effusions, primary tumors, and solid metastatic lesions from women with advanced-stage ovarian serous carcinoma. Endoglin expression was analyzed by immunohistochemistry in effusions (n = 211; 174 peritoneal, 37 pleural). Cellular endoglin staining was analyzed for association with the concentration of soluble endoglin (previously determined by ELISA) in 95 corresponding effusions and analyzed for correlation with clinicopathologic parameters, including survival. Endoglin expression was additionally studied in 34 patient-matched primary tumors and solid metastases. Carcinoma and mesothelial cells expressed endoglin in 95/211 (45%) and 133/211 (63%) effusions, respectively. Carcinoma cell endoglin expression was more frequent in effusions from patients aged ≤60 years (p = 0.048) and in post- compared to prechemotherapy effusions (p = 0.014), whereas mesothelial cell endoglin expression was higher in prechemotherapy effusions (p = 0.021). No association was found between cellular endoglin expression and its soluble effusion concentration. Endoglin was expressed in 17/34 (50%) primary tumors and 19/34 (56%) metastases, with significantly higher percentage of immunostained cells in solid metastases compared to effusions (p = 0.036). Endoglin expression did not correlate with survival. Tumor cell endoglin expression is higher in post- vs. prechemotherapy effusions, whereas the opposite is seen in mesothelial cells. Together with its upregulation in solid metastases, this suggests that the expression and biological role of endoglin may differ between cell populations and change along tumor progression in ovarian carcinoma

Towards image guided laparoscopic liver surgery, defining the system requirement

The first stage in the development of a surgical image guid- ance system should be the identification of the desired clinical outcomes. This paper identifies a set of desired clinical outcomes for a laparoscopic image guided liver surgery system. Working backwards from these a set of design goals and system parameters are identified. Knowledge of the important system parameters will allow system development to proceed in a controlled manner towards a system with maximal clinical benefit. After setting the system design goals and system parameters an image guidance system is proposed and details of development progress to date are given