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Abstract We report an extremely rare case of locally advanced prostate cancer in a phenotypic male patient with persistent müllerian duct syndrome. The patient underwent a robot-assisted retzius-sparing radical prostatectomy, bilateral pelvic lymph node dissection, radical hysterectomy, vaginectomy, and salpingo-ophorectomy. He was continent at 3 months follow-up. His follow-up PSA has steadily increased up to 1.4 ng/mL 6 months following surgery and his PSMA-PET scan showed bone metastasis with no local recurrence, and androgen deprivation therapy was started along with docetaxel chemotherapy. Prostate cancer in patients with DSD is extremely rare and can manifest itself with a low PSA, although aggressive cancer.

Objectives To evaluate the Versius surgical system for robot‐assisted prostatectomy in a preclinical cadaveric model using varying system setups and collect surgeon feedback on the performance of the system and instruments, in line with IDEAL‐D recommendations. Materials and methods Procedures were performed in cadaveric specimens by consultant urological surgeons to evaluate system performance in completing the surgical steps required for a prostatectomy. Procedures were conducted using either a 3‐arm or 4‐arm bedside unit (BSU) setup. Optimal port placements and BSU layouts were determined and surgeon feedback collected. Procedure success was defined as the satisfactory completion of all steps of the procedure, according to the operating surgeon. Results All four prostatectomies were successfully completed; two were completed with a 3‐arm BSU setup and two using a 4‐arm BSU setup. Small adjustments were made to the port and BSU positioning, according to surgeon preference, in order to complete the surgical steps. The surgeons noted some instrument difficulties with the Monopolar Curved Scissor tip and the Needle Holders, which were subsequently refined between the first and second sessions of the study, in line with surgeon feedback. Three cystectomies were also successfully completed, demonstrating the capability of the system to perform additional urological procedures. Conclusions This study provides a preclinical assessment of a next‐generation surgical robot for prostatectomies. All procedures were completed successfully, and port and BSU positions were validated, thus supporting the progression of the system to further clinical development according to the IDEAL‐D framework.

This work analyses the performance of Reinforcement Learning (RL) versus Swarm Intelligence (SI) for coordinating multiple unmanned High Altitude Platform Stations (HAPS) for communications area coverage. It builds upon previous work which looked at various elements of both algorithms. The main aim of this paper is to address the continuous state-space challenge within this work by using partitioning to manage the high dimensionality problem. This enabled comparing the performance of the classical cases of both RL and SI establishing a baseline for future comparisons of improved versions. From previous work, SI was observed to perform better across various key performance indicators. However, after tuning parameters and empirically choosing suitable partitioning ratio for the RL state space, it was observed that the SI algorithm still maintained superior coordination capability by achieving higher mean overall user coverage (about 20% better than the RL algorithm), in addition to faster convergence rates. Though the RL technique showed better average peak user coverage, the unpredictable coverage dip was a key weakness, making SI a more suitable algorithm within the context of this work.

The increased use of trickle or drip irrigation is seen as one way of helping to improve the sustainability of irrigation systems around the world. However, soil water and solute transport properties and soil profile characteristics are often not adequately incorporated in the design and management of trickle systems. In this paper, we describe results of a simulation study designed to highlight the impacts of soil properties on water and solute transport from buried trickle emitters. The analysis addresses the influence of soil hydraulic properties, soil layering, trickle discharge rate, irrigation frequency, and timing of nutrient application on wetting patterns and solute distribution. We show that (1) trickle irrigation can improve plant water availability in medium and low permeability fine-textured soils, providing that design and management are adapted to account for their soil hydraulic properties, (2) in highly permeable coarse-textured soils, water and nutrients move quickly downwards from the emitter, making it difficult to wet the near surface zone if emitters are buried too deep, and (3) changing the fertigation strategy for highly permeable coarse-textured soils to apply nutrients at the beginning of an irrigation cycle can maintain larger amounts of nutrient near to and above the emitter, thereby making them less susceptible to leaching losses. The results demonstrate the need to account for differences in soil hydraulic properties and solute transport when designing irrigation and fertigation management strategies. Failure to do this will result in inefficient systems and lost opportunities for reducing the negative environmental impacts of irrigation.

A number of angiogenic pathways have been implicated in urologic cancers, which could hold the key to developing antiangiogenic therapies against such tumors. Promoters and inhibitors of angiogenesis in tumors of the prostate, bladder and kidneys, and their use as either tumor markers or potential anticancer treatments, are reviewed in this article. Angiogenesis is critical for growth of tumors and their metastasis. In this article we review the literature on studies of angiogenesis pathways and markers for renal cancer, prostate cancer and bladder cancer. Overall, there is clear evidence that markers of angiogenesis and expression of angiogenic factors are associated with adverse outcomes in each of these tumor types. Relatively few angiogenic pathways have been investigated so far, although over 50 factors are known to be involved, and little has been studied on the antiangiogenic pathways and their suppression. The failing in many of the studies is small size and lack of suitable statistical analysis. Nevertheless, this review demonstrates the importance of these pathways and the need to develop selection criteria for patients who are candidates for antiangiogenic therapies. On the basis of the expression profiles reported so far, therapies that target vascular endothelial growth factor should be considered for the treatment of renal, prostate and bladder cancers. As most tumors express factors that are involved in multiple angiogenic pathways, further research is needed to determine which are coregulated and what the most common patterns are. Key Points Angiogenesis is essential for bladder, kidney and prostate cancer development Switch to an angiogenic phenotype occurs early in tumor development, and is stimulated by hypoxia, acidosis, inflammation and immune-cell activation Hypoxic stimulation leads to activation of many genes that promote tumor development through processes such as angiogenesis, glucose metabolism, cellular proliferation and pH regulation There are many proangiogenic factors, which include secreted proteins, transcription factors, cytokines, oncogenes, trace elements, proteases, enzymes and low-molecular-weight mediators There is clear evidence that the markers of angiogenesis (such as microvessel density) and expression of angiogenic factors (such as vascular endothelial growth factor) are related to adverse outcomes in bladder, kidney and prostate cancer Investigation into the many angiogenic and antiangiogenic pathways has been limited, and further study is essential to define the importance of these pathways and to develop selection criteria for patients who are candidates for antiangiogenic therapies

The autonomous coordinated flying for groups of unmanned aerial vehicles that maximise network coverage to mobile ground-based units by efficiently utilising the available on-board power is a complex problem. Their coordination involves the fulfilment of multiple objectives that are directly dependent on dynamic, unpredictable and uncontrollable phenomena. In this paper, two systems are presented and compared based on their ability to reposition fixed-wing unmanned aerial vehicles to maintain a useful airborne wireless network topology. Genetic algorithms and non-cooperative games are employed for the generation of optimal flying solutions. The two methods consider realistic kinematics for hydrocarbon-powered medium-altitude, long-endurance aircrafts. Coupled with a communication model that addresses environmental conditions, they optimise flying to maximising the number of supported ground-based units. Results of large-scale scenarios highlight the ability of genetic algorithms to evolve flexible sets of manoeuvres that keep the flying vehicles separated and provide optimal solutions over shorter settling times. In comparison, game theory is found to identify strategies of predefined manoeuvres that maximise coverage but require more time to converge.

One of the greatest challenges faced by irrigators using subsurface drip irrigation (SDI) is crop establishment. Establishment with SDI relies on unsaturated water movement from the buried source to the seed or seedling. Establishment is therefore affected by distance to source, soil texture, structure, and antecedent water content. Two products were compared (drip tape and CRZI - Capillary Root Zone Irrigation) in a field trial designed to address the establishment issue. To measure the widest establishment extent, a crop was sown perpendicular to the drip laterals. The CRZI system comprises a combination of both impermeable and highly conductive materials designed to produce a wider lateral wetting pattern, while reducing drainage and surface tunnelling. The hypothesis being tested was that the CRZI concept would offer some advantage over drip tape for addressing the establishment issue. Results showed that for the soil at the experimental site (Hanwood loam), installation depth of either product should be no greater than 0.2 m. If attempting to establish a broadsown crop such as lucerne or pasture, lateral spacing should be no greater than 1.0 m. With this configuration, an application depth of 120 mm should still be expected for total surface coverage. CRZI did not produce any establishment advantage over drip tape. Two explanations are given for this result. Firstly, the soil in which the trial was performed has excellent capillary properties and has a natural clay pan which would serve to even out results. Secondly, the two products exploited very different wetting methods to produce similar surface wetting efficiency (ratio of surface wetted width to applied irrigation volume). The drip tape quickly saturated the surface and wet outwards through surface flow. As CRZI did not utilise the surface to aid with distribution, it produced a slower, more even, wetting pattern.

This thesis considers the placement of two or more Unmanned Aerial Vehicles (UAVs) to provide communications to a community of ground mobiles. The locations for the UAVs are decided by the outcome of a non-cooperative game in which the UAVs compete to maximize their coverage of the mobiles. The game allows navigation decisions to be made onboard the UAVs with the effect of increasing coverage, reducing the need for a central planning function, and increasing the autonomy of the UAVs. A non-cooperative game that includes the key system elements is defined and simulated. The thesis compares methods for solving the game to evaluate their performance. A conflict between the quality of the solution and the time required to obtain that solution is identified and explored. It considers how the payload calculations could be used to modify the behaviour of the UAVs, and the sensitivity of the game to resource limitations such as RF power and radio spectrum. It finishes by addressing how the game could be scaled from two UAVs to many UAVs, and the constraints imposed by current methods for solving games.

Oxygen homeostasis and protection from episodes of low oxygen tension in human tissues is important for cell survival. There are a number of physiological and pathological scenarios that place the cell in hypoxic conditions warranting adaptation to the stressful environment. In hypoxia, oxidative phosphorylation is deceased with subsequent reduction of ATP production. A responsive increase in glycolysis compensates for this ATP reduction to some degree, but many ATP-dependent processes such as protein translation are decreased in hypoxic cells. Despite this, the cell must adapt to the hypoxic environment via increased oxygen delivery systemically and locally, as well as protect itself from secondary effects of hypoxia, such as decreased pH. Therefore, in a background of decreased total protein translation, specific upregulation of protective mechanisms safeguard the cell from hypoxic stress. This process is primarily regulated by a transcription factor known as Hypoxia Inducible Factor, HIF.

Introduction: Kidney Cancer accounts for approximately 2% of all new cancer diagnoses in the UK each year. Patient survival has improved over the past few decades; however the mechanisms of this are yet to be fully elucidated. Hypoxia inducible factor isoforms, HIF-1 and HIF-2, are constitutively expressed in many clear-cell RCCs due to loss of pVHL tumour suppressor function within the tumour. In vitro, HIF-1 and HIF-2 regulate a differential set of target genes, although their expression in primary ccRCC clinical samples and their effects on patient prognosis has yet to be fully understood. Methods: In this thesis analysis has been performed on all Nephrectomies performed at Oxford Radcliffe Hospitals for Renal Cell Carcinoma (RCC) from 1983 to 2007. Data extracted from Charlesworth Research Uro-Oncology Database, CRUD©, provided long-term survival data, maximal tumour diameter, Fuhrman grade, T-Staging and patient age. A subset of RCCs from this series (170 consecutive clear cell renal tumours from 1983 to 1999) were analysed within a tissue microarray and expression of HIF-1 and HIF-2, together with seven primary target genes (BNIP3, CAIX, CyclinD1, GLUT1, LDH5, Oct-4 and VEGF) was assessed. Comparison was made with tumour angiogenesis (CD31), tumour stage, Fuhrman grade, maximum tumour diameter and patient survival. Further work in this thesis analysed a series of paired VHL (functional and non-functional) ccRCC cell lines, assessing for hypoxic differential MicroRNA expression. Results: Analysis of 664 RCCs demonstrated a clear change in kidney cancer specific survival over the past 24 years, with 5-year survival improving from 42% (1983-1986) to 73% (1999- 2002). The incidence of RCC has increased 10 fold and has a significant association with 4-year survival. There was no significant change in operative mortality, patient age, Fuhrman grade, Pathological T-Stage or mean tumour size. However, there was a 5-fold increase in tumours <6cm, corresponding to an equal fold decrease in tumours 6-8cm, and no change in tumours >8cm. Tumour size >8cm was a significant prognostic marker. HIF-1 and HIF-2 showed no correlation and individually, neither HIF-1 nor HIF-2 expression had any prognostic utility; however a significant time-dependent deterioration of HIF-1 and HIF-2 antigenicity within paraffin blocks was identified. Angiogenesis (VVI CD31) had a strong negative correlation with Fuhrman grade and maximal tumour diameter and had prognostic significance, with high levels associated with good overall survival. Results from microRNA expression arrays found a specific microRNA (MiR-23a) that was differentially expressed depending upon VHL functionality and hypoxic conditions. Furthermore microRNA-23a was up-regulated in cells that expressed both HIF isoforms, and down-regulated in cells that only expressed HIF-2. Conclusions: Outcome following Nephrectomy for Renal Cell Carcinoma has dramatically improved over the past 24 years. Increasing incidence and decreasing tumour size at operation combined with the lack of statistical variation in Fuhrman grade, suggests that earlier detection of tumours offers subsequent curative treatment by Nephrectomy. Furthermore, stable incidence rates of tumours >8cm potentially represent alternative tumour biology, which grow rapidly, avoiding early detection and curative treatment. Although neither HIF isoform nor the seven HIF target genes was found to influence disease prognosis, the discovery of HIF antigenicity deterioration with time, is a very important finding and casts into doubt previous literature about HIF-1 immunostaining in human cancers. The prognostic significance of CD31+ angiogenesis appears initially counterintuitive, however, CD31+ endothelial cells may represent functional vessels which protect the tumour from sustained periods of ischaemia, unlike the low VVI group, from which hypoxia death-resistant clones could arise facilitating tumour metastasis. This could be very important when considering the effects of biologically targeted antiangiogenic therapies. Furthermore, the negative correlation with angiogenesis (CD31+) and Fuhrman grade suggests that vessel functionality and tumour aggressiveness may change with tumour size. The finding of a specific microRNA that appears to have VHL and HIF dependent expression extends our understanding of the hypoxic pathway and opens the possibility of further development of novel targeted therapies.