Should weight loss and maintenance programmes be designed differently for men? : A systematic review of long-term randomised controlled trials presenting data for men and women: The ROMEO project

Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved. Acknowledgements This review is one of a series of systematic reviews for the ROMEO project (Review Of MEn and Obesity), funded by the National Institute for Health Research, Health Technology Assessment Programme (NIHR HTA Project 09/127/01; Systematic reviews and integrated report on the quantitative and qualitative evidence base for the management of obesity in men http://www.hta.ac.uk/2545). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Department of Health. HERU, HSRU and NMAHP are funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The authors accept full responsibility for this publication. We would also like to thank the Men's Health Forums of Scotland, Ireland, England and Wales: Tim Street, Paula Carroll, Colin Fowler and David Wilkins. We also thank Kate Jolly for further information about the Lighten Up trial.

Should weight loss and maintenance programmes be designed differently for men? : A systematic review of long-term randomised controlled trials presenting data for men and women: The ROMEO project

Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved. Acknowledgements This review is one of a series of systematic reviews for the ROMEO project (Review Of MEn and Obesity), funded by the National Institute for Health Research, Health Technology Assessment Programme (NIHR HTA Project 09/127/01; Systematic reviews and integrated report on the quantitative and qualitative evidence base for the management of obesity in men http://www.hta.ac.uk/2545). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Department of Health. HERU, HSRU and NMAHP are funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The authors accept full responsibility for this publication. We would also like to thank the Men's Health Forums of Scotland, Ireland, England and Wales: Tim Street, Paula Carroll, Colin Fowler and David Wilkins. We also thank Kate Jolly for further information about the Lighten Up trial.

Resonance Energy Transfer-Based Molecular Switch Designed Using a Systematic Design Process Based on Monte Carlo Methods and Markov Chains

A RET network consists of a network of photo-active molecules called chromophores that can participate in inter-molecular energy transfer called resonance energy transfer (RET). RET networks are used in a variety of applications including cryptographic devices, storage systems, light harvesting complexes, biological sensors, and molecular rulers. In this dissertation, we focus on creating a RET device called closed-diffusive exciton valve (C-DEV) in which the input to output transfer function is controlled by an external energy source, similar to a semiconductor transistor like the MOSFET. Due to their biocompatibility, molecular devices like the C-DEVs can be used to introduce computing power in biological, organic, and aqueous environments such as living cells. Furthermore, the underlying physics in RET devices are stochastic in nature, making them suitable for stochastic computing in which true random distribution generation is critical.

In order to determine a valid configuration of chromophores for the C-DEV, we developed a systematic process based on user-guided design space pruning techniques and built-in simulation tools. We show that our C-DEV is 15x better than C-DEVs designed using ad hoc methods that rely on limited data from prior experiments. We also show ways in which the C-DEV can be improved further and how different varieties of C-DEVs can be combined to form more complex logic circuits. Moreover, the systematic design process can be used to search for valid chromophore network configurations for a variety of RET applications.

We also describe a feasibility study for a technique used to control the orientation of chromophores attached to DNA. Being able to control the orientation can expand the design space for RET networks because it provides another parameter to tune their collective behavior. While results showed limited control over orientation, the analysis required the development of a mathematical model that can be used to determine the distribution of dipoles in a given sample of chromophore constructs. The model can be used to evaluate the feasibility of other potential orientation control techniques.

Distributed Feature Selection in Large n and Large p Regression Problems

Fitting statistical models is computationally challenging when the sample size or the dimension of the dataset is huge. An attractive approach for down-scaling the problem size is to first partition the dataset into subsets and then fit using distributed algorithms. The dataset can be partitioned either horizontally (in the sample space) or vertically (in the feature space), and the challenge arise in defining an algorithm with low communication, theoretical guarantees and excellent practical performance in general settings. For sample space partitioning, I propose a MEdian Selection Subset AGgregation Estimator ({\em message}) algorithm for solving these issues. The algorithm applies feature selection in parallel for each subset using regularized regression or Bayesian variable selection method, calculates the `median' feature inclusion index, estimates coefficients for the selected features in parallel for each subset, and then averages these estimates. The algorithm is simple, involves very minimal communication, scales efficiently in sample size, and has theoretical guarantees. I provide extensive experiments to show excellent performance in feature selection, estimation, prediction, and computation time relative to usual competitors.

While sample space partitioning is useful in handling datasets with large sample size, feature space partitioning is more effective when the data dimension is high. Existing methods for partitioning features, however, are either vulnerable to high correlations or inefficient in reducing the model dimension. In the thesis, I propose a new embarrassingly parallel framework named {\em DECO} for distributed variable selection and parameter estimation. In {\em DECO}, variables are first partitioned and allocated to m distributed workers. The decorrelated subset data within each worker are then fitted via any algorithm designed for high-dimensional problems. We show that by incorporating the decorrelation step, DECO can achieve consistent variable selection and parameter estimation on each subset with (almost) no assumptions. In addition, the convergence rate is nearly minimax optimal for both sparse and weakly sparse models and does NOT depend on the partition number m. Extensive numerical experiments are provided to illustrate the performance of the new framework.

For datasets with both large sample sizes and high dimensionality, I propose a new "divided-and-conquer" framework {\em DEME} (DECO-message) by leveraging both the {\em DECO} and the {\em message} algorithm. The new framework first partitions the dataset in the sample space into row cubes using {\em message} and then partition the feature space of the cubes using {\em DECO}. This procedure is equivalent to partitioning the original data matrix into multiple small blocks, each with a feasible size that can be stored and fitted in a computer in parallel. The results are then synthezied via the {\em DECO} and {\em message} algorithm in a reverse order to produce the final output. The whole framework is extremely scalable.

Characterization of New Carbosilane Liquid Crystalline Monomers and Dimers

‘De Vries-like’ smectic liquid crystals exhibit low layer contraction of approximately 1% on transitions from the SmA to the SmC phase. These materials have received considerable attention as potential solutions for problems affecting liquid crystal displays using surface-stabilized ferroelectric liquid crystals (SSFLC). In SSFLCs, layer contraction of 710% is normally observed during the SmA to SmC phase transition. A study by the Lemieux group has shown that liquid crystals with nanosegregating carbosilane segments exhibit enhanced ‘de Vries-like’ properties through the formation of smectic layers and by lengthening the nanosegregating carbosilane end-groups from monocarbosilane to tricarbosilane. This observed enhancement is assumed to be due to an increase in the cross-section of the free volume in the hydrocarbon sub-layer. To test this hypothesis, it is assumed that dimers with a tricarbosilane linking group have smaller cross-sections on time average. In his thesis, this hypothesis is tested through the characterization of new liquid crystalline monomers (QL39-n) and dimers (QL40-n) with 2-phenylpyrimidine cores and tricarbosilane end-groups and spacers, respectively. The thesis describes the synthesis of two homologous series of liquid crystals and their characterization using a variety of techniques, including polarized optical microscopy, differential scanning calorimetry and X-ray diffraction. The results show that the monomers QL39-n form a tilted SmC phase only, whereas the dimers QL40-n form an orthogonal SmA phase. These results are discussed in the context of our hypothesis.

The Views of Young People about an Intervention Programme Designed to Support Them with Exam Related Anxiety and Stress

Both preparing for and sitting exams can be extremely stressful for children and young people. Whilst the research within the area of exam anxiety acknowledges the detrimental impact that it can have on individuals, much of the research has been completed with university students. Limited research has been carried out with children and young people. In addition to this, there is also little research that has been completed in order to understand which interventions are helpful in reducing exam anxiety in young people. The systematic literature review highlighted that much of the research employed quantitative techniques. This means young people’s views and experiences of exam anxiety has largely been unexplored. The EPS service in which the TEP currently works is a partially traded service. Some of the schools that had bought a service level agreement requested support for certain pupils that were experiencing exam anxiety. The EPS service therefore delivered an intervention called ‘beating exam anxiety together’ (further details of this intervention can be found within chapter 1). Seven semi-structured interviews were carried out with GCSE students who took part in the ‘beating exam anxiety together’ intervention. The purpose of the interviews was to understand more about young people’s views on exam anxiety, and also their experiences of the intervention in which they took part. The research highlighted the possible detrimental impact of exam anxiety on young people in terms of their mental health, and also how able they feel to prepare for their exams. The results of the research interestingly showed that young people experience high levels of pressure from school teachers and also their parents. Furthermore, students reported that they didn't know how to revise. The results revealed that young people feel that the way in which exams are spoken about in schools is largely negative. As a result of this, the researcher suggested that it may be helpful to shift the narrative around the way in which exams are currently spoken about. In addition to this, the results indicate that the intervention was largely helpful in improving young people’s well being and their ability to be able to manage exam anxiety.

"Everything was designed to make sure that this thing endured" : Processus de légitimation et la Responsabilité de protéger

L’objet de cette thèse est la « Responsabilité de protéger » (RdP), son émergence et les processus de légitimation qui ont contribué à son acceptation dans les arènes de la politique globale. Le principe d’une intervention militaire à des fins humanitaires gagne en légitimité dans les années 1990, bien qu’il soit marqué par d’intenses polémiques dans la pratique. Les situations de conflits où les civils sont brutalement persécutés et les interventions demandées et organisées pour y répondre sont maintenant largement justifiées dans les termes de la RdP. Est donc apparu d’abord un changement normatif. Ce changement s’est cristallisé dans le rapport de la Commission internationale sur l’intervention et la souveraineté des États (CIISE) qui a forgé l’expression « responsabilité de protéger ». Le point de départ ici est cependant que la RdP marque un changement discursif dans la manière de parler et de justifier ces pratiques. Je montre comment les termes de la RdP en sont venus à être ceux qui dégagent le plus large consensus autour de la question de l’intervention à des fins humanitaires. La thèse centrale de cette recherche est que le relatif succès de la RdP tient au fait que les architectes de la CIISE et les entrepreneurs de la RdP ont déployé un sens pratique aiguisé du champ de la politique globale. Le procédé principal employé est de mettre en lumière les processus de légitimation activement mis en oeuvre pour stimuler ce changement discursif. J’avance que les agents ont su placer la RdP, et par extension le principe de l’intervention à des fins humanitaires, dans le domaine du non problématique en déployant un langage et des pratiques vus comme ne posant pas problème. Concrètement, il s’est agi de choisir les agents à qui serait accordée la reconnaissance de parler, mais qui seraient aussi en mesure de proposer une solution d’une manière considérée comme légitime dans les arènes de la politique globale. Traquer les processus de légitimation est un procédé analytique qui permet de comprendre le succès de la RdP, mais qui révèle également des éléments fondamentaux du fonctionnement formel et informel de la politique globale.

Security through Obscurity: Layout Obfuscation of Digital Integrated Circuits using Don't Care Conditions

Contemporary integrated circuits are designed and manufactured in a globalized environment leading to concerns of piracy, overproduction and counterfeiting. One class of techniques to combat these threats is circuit obfuscation which seeks to modify the gate-level (or structural) description of a circuit without affecting its functionality in order to increase the complexity and cost of reverse engineering. Most of the existing circuit obfuscation methods are based on the insertion of additional logic (called “key gates”) or camouflaging existing gates in order to make it difficult for a malicious user to get the complete layout information without extensive computations to determine key-gate values. However, when the netlist or the circuit layout, although camouflaged, is available to the attacker, he/she can use advanced logic analysis and circuit simulation tools and Boolean SAT solvers to reveal the unknown gate-level information without exhaustively trying all the input vectors, thus bringing down the complexity of reverse engineering. To counter this problem, some ‘provably secure’ logic encryption algorithms that emphasize methodical selection of camouflaged gates have been proposed previously in literature [1,2,3]. The contribution of this paper is the creation and simulation of a new layout obfuscation method that uses don't care conditions. We also present proof-of-concept of a new functional or logic obfuscation technique that not only conceals, but modifies the circuit functionality in addition to the gate-level description, and can be implemented automatically during the design process. Our layout obfuscation technique utilizes don’t care conditions (namely, Observability and Satisfiability Don’t Cares) inherent in the circuit to camouflage selected gates and modify sub-circuit functionality while meeting the overall circuit specification. Here, camouflaging or obfuscating a gate means replacing the candidate gate by a 4X1 Multiplexer which can be configured to perform all possible 2-input/ 1-output functions as proposed by Bao et al. [4]. It is important to emphasize that our approach not only obfuscates but alters sub-circuit level functionality in an attempt to make IP piracy difficult. The choice of gates to obfuscate determines the effort required to reverse engineer or brute force the design. As such, we propose a method of camouflaged gate selection based on the intersection of output logic cones. By choosing these candidate gates methodically, the complexity of reverse engineering can be made exponential, thus making it computationally very expensive to determine the true circuit functionality. We propose several heuristic algorithms to maximize the RE complexity based on don’t care based obfuscation and methodical gate selection. Thus, the goal of protecting the design IP from malicious end-users is achieved. It also makes it significantly harder for rogue elements in the supply chain to use, copy or replicate the same design with a different logic. We analyze the reverse engineering complexity by applying our obfuscation algorithm on ISCAS-85 benchmarks. Our experimental results indicate that significant reverse engineering complexity can be achieved at minimal design overhead (average area overhead for the proposed layout obfuscation methods is 5.51% and average delay overhead is about 7.732%). We discuss the strengths and limitations of our approach and suggest directions that may lead to improved logic encryption algorithms in the future. References: [1] R. Chakraborty and S. Bhunia, “HARPOON: An Obfuscation-Based SoC Design Methodology for Hardware Protection,” IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems, vol. 28, no. 10, pp. 1493–1502, 2009. [2] J. A. Roy, F. Koushanfar, and I. L. Markov, “EPIC: Ending Piracy of Integrated Circuits,” in 2008 Design, Automation and Test in Europe, 2008, pp. 1069–1074. [3] J. Rajendran, M. Sam, O. Sinanoglu, and R. Karri, “Security Analysis of Integrated Circuit Camouflaging,” ACM Conference on Computer Communications and Security, 2013. [4] Bao Liu, Wang, B., "Embedded reconfigurable logic for ASIC design obfuscation against supply chain attacks,"Design, Automation and Test in Europe Conference and Exhibition (DATE), 2014 , vol., no., pp.1,6, 24-28 March 2014.

Biomimetic Scaffold with Aligned Microporosity Designed for Dentin Regeneration

Tooth loss is a common result of a variety of oral diseases due to physiological causes, trauma, genetic disorders, and aging and can lead to physical and mental suffering that markedly lowers the individual’s quality of life. Tooth is a complex organ that is composed of mineralized tissues and soft connective tissues. Dentin is the most voluminous tissue of the tooth and its formation (dentinogenesis) is a highly regulated process displaying several similarities with osteogenesis. In this study, gelatin, thermally denatured collagen, was used as a promising low-cost material to develop scaffolds for hard tissue engineering. We synthetized dentin-like scaffolds using gelatin biomineralized with magnesium-doped hydroxyapatite and blended it with alginate. With a controlled freeze-drying process and alginate cross-linking, it is possible to obtain scaffolds with microscopic aligned channels suitable for tissue engineering. 3D cell culture with mesenchymal stem cells showed the promising properties of the new scaffolds for tooth regeneration. In detail, the chemical–physical features of the scaffolds, mimicking those of natural tissue, facilitate the cell adhesion, and the porosity is suitable for long-term cell colonization and fine cell–material interactions.

Classic Nintendo games are (computationally) hard

We prove NP-hardness results for five of Nintendo's largest video game franchises: Mario, Donkey Kong, Legend of Zelda, Metroid, and Pokémon. Our results apply to generalized versions of Super Mario Bros.1-3, The Lost Levels, and Super Mario World; Donkey Kong Country 1-3; all Legend of Zelda games; all Metroid games; and all Pokémon role-playing games. In addition, we prove PSPACE-completeness of the Donkey Kong Country games and several Legend of Zelda games.

Variational ensemble Kalman filtering applied to data assimilation problems in computational fluid dynamics

One challenge on data assimilation (DA) methods is how the error covariance for the model state is computed. Ensemble methods have been proposed for producing error covariance estimates, as error is propagated in time using the non-linear model. Variational methods, on the other hand, use the concepts of control theory, whereby the state estimate is optimized from both the background and the measurements. Numerical optimization schemes are applied which solve the problem of memory storage and huge matrix inversion needed by classical Kalman filter methods. Variational Ensemble Kalman filter (VEnKF), as a method inspired the Variational Kalman Filter (VKF), enjoys the benefits from both ensemble methods and variational methods. It avoids filter inbreeding problems which emerge when the ensemble spread underestimates the true error covariance. In VEnKF this is tackled by resampling the ensemble every time measurements are available. One advantage of VEnKF over VKF is that it needs neither tangent linear code nor adjoint code. In this thesis, VEnKF has been applied to a two-dimensional shallow water model simulating a dam-break experiment. The model is a public code with water height measurements recorded in seven stations along the 21:2 m long 1:4 m wide flume’s mid-line. Because the data were too sparse to assimilate the 30 171 model state vector, we chose to interpolate the data both in time and in space. The results of the assimilation were compared with that of a pure simulation. We have found that the results revealed by the VEnKF were more realistic, without numerical artifacts present in the pure simulation. Creating a wrapper code for a model and DA scheme might be challenging, especially when the two were designed independently or are poorly documented. In this thesis we have presented a non-intrusive approach of coupling the model and a DA scheme. An external program is used to send and receive information between the model and DA procedure using files. The advantage of this method is that the model code changes needed are minimal, only a few lines which facilitate input and output. Apart from being simple to coupling, the approach can be employed even if the two were written in different programming languages, because the communication is not through code. The non-intrusive approach is made to accommodate parallel computing by just telling the control program to wait until all the processes have ended before the DA procedure is invoked. It is worth mentioning the overhead increase caused by the approach, as at every assimilation cycle both the model and the DA procedure have to be initialized. Nonetheless, the method can be an ideal approach for a benchmark platform in testing DA methods. The non-intrusive VEnKF has been applied to a multi-purpose hydrodynamic model COHERENS to assimilate Total Suspended Matter (TSM) in lake Säkylän Pyhäjärvi. The lake has an area of 154 km2 with an average depth of 5:4 m. Turbidity and chlorophyll-a concentrations from MERIS satellite images for 7 days between May 16 and July 6 2009 were available. The effect of the organic matter has been computationally eliminated to obtain TSM data. Because of computational demands from both COHERENS and VEnKF, we have chosen to use 1 km grid resolution. The results of the VEnKF have been compared with the measurements recorded at an automatic station located at the North-Western part of the lake. However, due to TSM data sparsity in both time and space, it could not be well matched. The use of multiple automatic stations with real time data is important to elude the time sparsity problem. With DA, this will help in better understanding the environmental hazard variables for instance. We have found that using a very high ensemble size does not necessarily improve the results, because there is a limit whereby additional ensemble members add very little to the performance. Successful implementation of the non-intrusive VEnKF and the ensemble size limit for performance leads to an emerging area of Reduced Order Modeling (ROM). To save computational resources, running full-blown model in ROM is avoided. When the ROM is applied with the non-intrusive DA approach, it might result in a cheaper algorithm that will relax computation challenges existing in the field of modelling and DA.

Synthesis and structural stability of metal-organic frameworks

Metal-organic frameworks (MOFs) have attracted significant attention during the past decade due to their high porosity, tunable structures, and controllable surface functionalities. Therefore many applications have been proposed for MOFs. All of them however are still in their infancy stage and have not yet been brought into the market place. In this thesis, the background of the MOF area is first briefly introduced. The main components and the motifs of designing MOFs are summarized, followed by their synthesis and postsynthetic modification methods. Several promising application areas of MOFs including gas storage and separation, catalysis and sensing are reviewed. The current status of commercialization of MOFs as new chemical products is also summarized. Examples of the design and synthesis of two new MOF structures Eu(4,4′,4′′,4′′′-(porphine-5,10,15,20-tetrayl)tetrakis(benzoic acid))·2H2O∙xDMF and Zn4O(azobenzene-4,4’-dicarboxylic acid)3∙xNMP are described. The first one contains free-base porphyrin centers and the second one has azobenzene components. Although the structures were synthesized as designed, unfortunately they did not possess the expected properties. The research idea to use MOFs as template materials to synthesize porous polymers is introduced. Several methods are discussed to grow PMMA into IRMOF-1 (Zn4O(benzene-1,4-dicarboxylate)3, IR stands for isoreticular) structure. High concentration of the monomers resulted in PMMA shell after MOF digestion while with low concentration of monomers no PMMA was left after digestion due to the small iii molecular weight. During the study of this chapter, Kitagawa and co-workers published several papers on the same topic, so this part of the research was terminated thereafter. Many MOFs are reported to be unstable in air due to the water molecules in air which greatly limited their applications. By incorporating a number of water repelling functional groups such as trifluoromethoxy group and methyl groups in the frameworks, the water stability of MOFs are shown to be significantly enhanced. Several MOFs inculding Banasorb-22 (Zn4O(2-trifluoromethoxybenzene-1,4-dicarboxylate)3), Banasorb-24 (Zn4O(2, 5-dimethylbenzene-1,4-dicarboxylate)3) and Banasorb-30 (Zn4O(2-methylbenzene-1,4-dicarboxylate)3) were synthesized and proved to have isostructures with IRMOF-1. Banasorb-22 was stable in boiling water steam for one week and Banasorb-30’s shelf life was over 10 months under ambient condition. For comparison, IRMOF-1’s structure collapses in air after a few hours to several days. Although MOF is a very popular research area nowadays, only a few studies have been reported on the mechanical properties of MOFs. Many of MOF’s applications involve high pressure conditions, so it is important to understand the behavior of MOFs under elivated pressures. The mechanical properties of IRMOF-1 and a new MOF structure Eu2(C12N2O4H6)3(DEF)0.87(H2O)2.13 were studied using diamond anvil cells at Advanced Photon Source. IRMOF-1 experienced an irriversible phase transtion to a nonporous phase followed by amorphization under high pressure. Eu2(C12N2O4H6)3(DEF)0.87(H2O)2.13 showed reversible compression under pressure up to 9.08GPa.

Asymptotic preserving and time diminishing schemes for rarefied gas dynamic

In this work, we introduce a new class of numerical schemes for rarefied gas dynamic problems described by collisional kinetic equations. The idea consists in reformulating the problem using a micro-macro decomposition and successively in solving the microscopic part by using asymptotic preserving Monte Carlo methods. We consider two types of decompositions, the first leading to the Euler system of gas dynamics while the second to the Navier-Stokes equations for the macroscopic part. In addition, the particle method which solves the microscopic part is designed in such a way that the global scheme becomes computationally less expensive as the solution approaches the equilibrium state as opposite to standard methods for kinetic equations which computational cost increases with the number of interactions. At the same time, the statistical error due to the particle part of the solution decreases as the system approach the equilibrium state. This causes the method to degenerate to the sole solution of the macroscopic hydrodynamic equations (Euler or Navier-Stokes) in the limit of infinite number of collisions. In a last part, we will show the behaviors of this new approach in comparisons to standard Monte Carlo techniques for solving the kinetic equation by testing it on different problems which typically arise in rarefied gas dynamic simulations.

Anti-Metastatic Properties of a Marine Bacterial Exopolysaccharide-Based Derivative Designed to Mimic Glycosaminoglycans

Osteosarcoma is the most frequent malignant primary bone tumor characterized by a high potency to form lung metastases. In this study, the effect of three oversulfated low molecular weight marine bacterial exopolysaccharides (OS-EPS) with different molecular weights (4, 8 and 15 kDa) were first evaluated in vitro on human and murine osteosarcoma cell lines. Different biological activities were studied: cell proliferation, cell adhesion and migration, matrix metalloproteinase expression. This in vitro study showed that only the OS-EPS 15 kDa derivative could inhibit the invasiveness of osteosarcoma cells with an inhibition rate close to 90%. Moreover, this derivative was potent to inhibit both migration and invasiveness of osteosarcoma cell lines; had no significant effect on their cell cycle; and increased slightly the expression of MMP-9, and more highly the expression of its physiological specific tissue inhibitor TIMP-1. Then, the in vivo experiments showed that the OS-EPS 15 kDa derivative had no effect on the primary osteosarcoma tumor induced by osteosarcoma cell lines but was very efficient to inhibit the establishment of lung metastases in vivo. These results can help to better understand the mechanisms of GAGs and GAG-like derivatives in the biology of the tumor cells and their interactions with the bone environment to develop new therapeutic strategies.