Towards realising multimodal robots

Evolutionary Algorithms (EAs) have been applied in co-evolutionary robotics over the last quarter century. They simultaneously generate the robot body morphology and controller algorithm through artificial evolution. However, the literature shows that in this area, it is still not possible to generate robots that perform better than conventional manual designs, even for simple tasks. This thesis describes steps undertaken to improve the co-evolution process. The investigation concerns two key areas of co-evolutionary robotics. The first is in fitness function development, which plays an integral part in selecting parents for mating during evolution. The effect of an incremental fitness function based on established algorithmic techniques from specific task domains of robotics is studied. An A-star algorithm-based fitness function for path planning is designed and implemented for co- evolution of robots for navigation and obstacle avoidance. Results show that the trajectories of robots that reach a goal using the A-star algorithm-based fitness function are shorter than the robots evolved with a basic distance-based fitness function. The second area of study is the role of the controller evolution in the co-evolution process. Inspired by natural paradigms of evolution coupled with learning in biological organisms, a Reinforced Co-evolutionary Algorithm (ReCoAl) is proposed. ReCoAl works by allowing a direct policy gradient based Reinforcement Learning algorithm to improve the controller of every evolved robot to better utilise the available morphological resources before the fitness evaluation. The findings indicate that the learning process has both positive and negative effects on the progress of evolution, similar to observations in evolutionary biology

Effect of electron beam irradiation on structural and optical properties of Cu-doped In2O3 films prepared by RF magnetron sputtering.

Undoped and Cu-doped In2O3 films were prepared by radiofrequency magnetron sputtering technique. The effects of Cu doping and high-energy electron beam irradiation on the structural and optical properties of as-prepared films were investigated using techniques such as x-ray diffraction, x-ray photoelectron spectroscopy (XPS), lateral scanning electron microscopic image analysis, energy-dispersive x-ray (EDX) spectroscopy, micro-Raman, and ultraviolet-visible (UV-vis) spectroscopy. Moderate doping of Cu in In2O3 enhanced the intensity of (222) peak, indicating alignment of crystalline grains along . Electron beam irradiation promoted orientation of crystalline grains along in undoped and moderately Cu-doped films. EDX spectroscopic and XPS analyses revealed incorporation of Cu2+ ions in the lattice. The transmittance of Cu-doped films decreased with e-beam irradiation. Systematic reduction of the bandgap energy with an increase in Cu doping concentration was seen in unirradiated and electron-beam-irradiated films

DEVELOPMENT OF OSMOTICALLY CONTROLLED ORAL DRUG DELIVERY SYSTEM FOR NATEGLINIDE AN ANTI-DIABETIC DRUG

Objective: The purpose of the present study was to develop an oral push-pull osmotic drug delivery system for the drug Nateglinide which is a bio pharmaceutics classification system (BCS) class II drug. Methods: The tablets were prepared by the wet granulation method using ingredients microcrystalline cellulose (Adsorbent), potassium chloride (Osmotic agent), poly ethylene glycol (4000 and 6000) (Hydrophilic polymer, Plasticizer), starch (Disintegrant), and aerosil. The granules were compacted by double compression method and were coated with eudragit by dipping method. Different batches were prepared to study the effect of the various ingredients and their effect on the release of the drug from the system by varying the concentrations of the ingredients in each batch. Dissolution was assessed using USP dissolution apparatus 2 in phosphate buffer pH 6.8 for 12 h. Results: Certain key findings observed includes a decrease in micro crystalline cellulose content reduced the release of the drug due to the reduction of the hydrophilic content in the tablet which complements the uptake of water from the surroundings, and increase in the ethylene glycol leads to decrease in the release which resulted due to excess swelling and increase in the osmotic agent concentration lead to satisfactory release of the drug and followed zero-order release. Conclusion: To conclude, the push-pull osmotic tablet of Nateglinide was able to deliver the drug in a controlled pattern for a prolonged period of time. This type of formulation can be used in conditions like hyperglycemia where the patient compliance can improve by reducing the dosing frequency and the plasma drug levels can be maintained, the total drug load is also reduced so that the dose related side-effects are also reduced. Keywords: Controlled release, Push-pull osmotic pump, Nateglinid

LNCS

We present an algorithmic method for the quantitative, performance-aware synthesis of concurrent programs. The input consists of a nondeterministic partial program and of a parametric performance model. The nondeterminism allows the programmer to omit which (if any) synchronization construct is used at a particular program location. The performance model, specified as a weighted automaton, can capture system architectures by assigning different costs to actions such as locking, context switching, and memory and cache accesses. The quantitative synthesis problem is to automatically resolve the nondeterminism of the partial program so that both correctness is guaranteed and performance is optimal. As is standard for shared memory concurrency, correctness is formalized "specification free", in particular as race freedom or deadlock freedom. For worst-case (average-case) performance, we show that the problem can be reduced to 2-player graph games (with probabilistic transitions) with quantitative objectives. While we show, using game-theoretic methods, that the synthesis problem is Nexp-complete, we present an algorithmic method and an implementation that works efficiently for concurrent programs and performance models of practical interest. We have implemented a prototype tool and used it to synthesize finite-state concurrent programs that exhibit different programming patterns, for several performance models representing different architectures

Proposal for the delineation of neoadjuvant target volumes in oesophageal cancer

PURPOSE: To define instructions for delineation of target volumes in the neoadjuvant setting in oesophageal cancer. MATERIALS AND METHODS: Radiation oncologists of five European centres participated in the following consensus process: [1] revision of published (MEDLINE) and national/institutional delineation guidelines; [2] first delineation round of five cases (patient 1-5) according to national/institutional guidelines; [3] consensus meeting to discuss the results of step 1 and 2, followed by a target volume delineation proposal; [4] circulation of proposed instructions for target volume delineation and atlas for feedback; [5] second delineation round of five new cases (patient 6-10) to peer review and validate (two additional centres) the agreed delineation guidelines and atlas; [6] final consensus on the delineation guidelines depicted in an atlas. Target volumes of the delineation rounds were compared between centres by Dice similarity coefficient (DSC) and maximum/mean undirected Hausdorff distances (Hmax/Hmean). RESULTS: In the first delineation round, the consistency between centres was moderate (CTVtotal: DSC = 0.59-0.88; Hmean = 0.2-0.4 cm). Delineations in the second round were much more consistent. Lowest variability was obtained between centres participating in the consensus meeting (CTVtotal: DSC: p < 0.050 between rounds for patients 6/7/8/10; Hmean: p < 0.050 for patients 7/8/10), compared to validation centres (CTVtotal: DSC: p < 0.050 between validation and consensus meeting centres for patients 6/7/8; Hmean: p < 0.050 for patients 7/10). A proposal for delineation of target volumes and an atlas were generated. CONCLUSION: We proposed instructions for target volume delineation and an atlas for the neoadjuvant radiation treatment in oesophageal cancer. These will enable a more uniform delineation of patients in clinical practice and clinical trials

Efficacy of early PET-CT directed switch to carboplatin and paclitaxel based definitive chemoradiotherapy in patients with oesophageal cancer who have a poor early response to induction cisplatin and capecitabine in the UK: a multi-centre randomised controlled phase II trial induction cisplatin and capecitabine in the UK: a multi-centre randomised controlled phase II trial

Background: The utility of early metabolic response assessment to guide selection of the systemic component of definitive chemoradiotherapy (dCRT) for oesophageal cancer is uncertain.// Methods: In this multi-centre, randomised, open-label, phase II substudy of the radiotherapy dose-escalation SCOPE2 trial we evaluated the role of 18F-Fluorodeoxyglucose positron emission tomography (PET) at day 14 of cycle 1 of three-weekly induction cis/cap (cisplatin (60 mg/m2)/capecitabine (625 mg/m2 days 1–21)) in patients with oesophageal squamous cell carcinoma (OSCC) or adenocarcinoma (OAC). Non-responders, who had a less than 35% reduction in maximum standardised uptake value (SUVmax) from pre-treatment baseline, were randomly assigned to continue cis/cap or switch to car/pac (carboplatin AUC 5/paclitaxel 175 mg/m2) for a further induction cycle, then concurrently with radiotherapy over 25 fractions. Responders continued cis/cap for the duration of treatment. All patients (including responders) were randomised to standard (50Gy) or high (60Gy) dose radiation as part of the main study. Primary endpoint for the substudy was treatment failure-free survival (TFFS) at week 24. The trial was registered with International Standard Randomized Controlled Trial Number 97125464 and ClinicalTrials.gov NCT02741856.// Findings: This substudy was closed on 1st August 2021 by the Independent Data Monitoring Committee on the grounds of futility and possible harm. To this point from 22nd November 2016, 103 patients from 16 UK centres had participated in the PET-CT substudy; 63 (61.2%; 52/83 OSCC, 11/20 OAC) of whom were non-responders. Of these, 31 were randomised to car/pac and 32 to remain on cis/cap. All patients were followed up until at least 24 weeks, at which point in OSCC both TFFS (25/27 (92.6%) vs 17/25 (68%); p = 0.028) and overall survival (42.5 vs. 20.4 months, adjusted HR 0.36; p = 0.018) favoured cis/cap over car/pac. There was a trend towards worse survival in OSCC + OAC cis/cap responders (33.6 months; 95%CI 23.1-nr) vs. non-responders (42.5 (95%CI 27.0-nr) months; HR = 1.43; 95%CI 0.67–3.08; p = 0.35).// Interpretation: In OSCC, early metabolic response assessment is not prognostic for TFFS or overall survival and should not be used to personalise systemic therapy in patients receiving dCRT

Conformity analysis to demonstrate reproducibility of target volumes for Margin-Intense Stereotactic Radiotherapy for borderline-resectable pancreatic cancer.

Margin-directed neoadjuvant radiotherapy for borderline-resectable pancreatic cancer (BRPC) aims to facilitate clear surgical margins. A systematic method was developed for definition of a boost target volume prior to a formal phase-I study.Reference structures were defined by two oncologists and one radiologist, target structures were submitted by eight oncologist investigators and compared using conformity indices. Resultant risk of duodenal bleed (NTCP) was modelled.For GTV, reference volume was 2.1cm(3) and investigator mean was 6.03cm(3) (95% CI 3.92-8.13cm(3)), for boost volume 1.1cm(3) and 1.25cm(3) (1.02-1.48cm(3)). Mean Dice conformity coefficient for GTV was 0.47 (0.38-0.56), and for boost volume was significantly higher at 0.61 (0.52-0.70, p=0.01). Discordance index (DI) for GTV was 0.65 (0.56-0.75) and for boost volume was significantly lower at 0.39 (0.28-0.49, p=0.001). NTCP using reference contours was 2.95%, with mean for investigator contour plans 3.93% (3.63-4.22%). Correlations were seen between NTCP and GTV volume (p=0.02) and NTCP and DI (correlation coefficient 0.83 (0.29-0.97), p=0.01).Better conformity with reference was shown for boost volume compared with GTV. Investigator GTV volumes were larger than reference, had higher DI scores and modelled toxicity risk. A consistent method of target structure definition for margin-directed pancreatic radiotherapy is demonstrated

Treatment planning comparison in the PROTECT-trial randomising proton versus photon beam therapy in oesophageal cancer:Results from eight European centres

PURPOSE To compare dose distributions and robustness in treatment plans from eight European centres in preparation for the European randomized phase-III PROTECT-trial investigating the effect of proton therapy (PT) versus photon therapy (XT) for oesophageal cancer. MATERIALS AND METHODS All centres optimized one PT and one XT nominal plan using delineated 4DCT scans for four patients receiving 50.4 Gy (RBE) in 28 fractions. Target volume receiving 95% of prescribed dose (V95%iCTVtotal) should be >99%. Robustness towards setup, range, and respiration was evaluated. The plans were recalculated on a surveillance 4DCT (sCT) acquired at fraction ten and robustness evaluation was performed to evaluate the effect of respiration and inter-fractional anatomical changes. RESULTS All PT and XT plans complied with V95%iCTVtotal >99% for the nominal plan and V95%iCTVtotal >97% for all respiratory and robustness scenarios. Lung and heart dose varied considerably between centres for both modalities. The difference in mean lung dose and mean heart dose between each pair of XT and PT plans was in median [range] 4.8 Gy [1.1;7.6] and 8.4 Gy [1.9;24.5], respectively. Patients B and C showed large inter-fractional anatomical changes on sCT. For patient B, the minimum V95%iCTVtotal in the worst-case robustness scenario was 45% and 94% for XT and PT, respectively. For patient C, the minimum V95%iCTVtotal was 57% and 72% for XT and PT, respectively. Patient A and D showed minor inter-fractional changes and the minimum V95%iCTVtotal was >85%. CONCLUSION Large variability in dose to the lungs and heart was observed for both modalities. Inter-fractional anatomical changes led to larger target dose deterioration for XT than PT plans

Respiratory-gated (4D) contrast-enhanced FDG PET-CT for radiotherapy planning of lower oesophageal carcinoma: Feasibility and impact on planning target volume

Background: To assess the feasibility and potential impact on target delineation of respiratory-gated (4D) contrast-enhanced 18 Fluorine fluorodeoxyglucose (FDG) positron emission tomography - computed tomography (PET-CT), in the treatment planning position, for a prospective cohort of patients with lower third oesophageal cancer. Methods: Fifteen patients were recruited into the study. Imaging included 4D PET-CT, 3D PET-CT, endoscopic ultrasound and planning 4D CT. Target volume delineation was performed on 4D CT, 4D CT with co-registered 3D PET and 4D PET-CT. Planning target volumes (PTV) generated with 4D CT (PTV 4DCT), 4D CT co-registered with 3D PET-CT (PTV 3DPET4DCT) and 4D PET-CT (PTV 4DPETCT ) were compared with multiple positional metrics. Results: Mean PTV 4DCT , PTV 3DPET4DCT and PTV 4DPETCT were 582.4 ± 275.1 cm 3 , 472.5 ± 193.1 cm 3 and 480.6 ± 236.9 cm 3 respectively (no significant difference). Median DICE similarity coefficients comparing PTV 4DCT with PTV 3DPET4DCT, PTV 4DCT with PTV 4DPETCT and PTV 3DPET4DCT with PTV 4DPETCT were 0.85 (range 0.65-0.9), 0.85 (range 0.69-0.9) and 0.88 (range 0.79-0.9) respectively. The median sensitivity index for overlap comparing PTV 4DCT with PTV 3DPET4DCT, PTV 4DCT with PTV 4DPETCT and PTV 3DPET4DCT with PTV 4DPETCT were 0.78 (range 0.65-0.9), 0.79 (range 0.65-0.9) and 0.89 (range 0.68-0.94) respectively. Conclusions: Planning 4D PET-CT is feasible with careful patient selection. PTV generated using 4D CT, 3D PET-CT and 4D PET-CT were of similar volume, however, overlap analysis demonstrated that approximately 20% of PTV 3DPETCT and PTV 4DPETCT are not included in PTV 4DCT , leading to under-coverage of target volume and a potential geometric miss. Additionally, differences between PTV 3DPET4DCT and PTV 4DPETCT suggest a potential benefit for 4D PET-CT. Trial registration: ClinicalTrials.gov Identifier - NCT02285660(Registered 21/10/2014)

Reply to Comment on "The UK consensus position on the treatment of pancreatic cancer during the COVID-19 pandemic".

Funder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/50110000028