An 18Ni (C-250) maraging steel was successfully processed by equal channel angular pressing (ECAP) for a single pass at room temperature. Microstructural observations showed that the martensite laths of 18Ni maraging steel were elongated to more narrow bands with a width of 100-200 nm after ECAP deformation. After ageing treatment, many nano-sized precipitates distributed uniformly within the refined martensite lathes. In comparison with the tensile strength (1940 MPa) of general used steel (solution + aging treatment), the tensile strength of the sample processed by ECAP and subsequent aging treatment was enhanced for more than 100 MPa (above 2050 MPa). The enhancement of tensile properties was attributed to microstructural refinement and uniformly distributed nano-precipitates.


The time duration in continuous time Bayesian networks, i.e., the time that a variable stays in a state until it transitions to another state, follows an exponential distribution. The exponential distribution is widely applied to describe the waiting time between events in a Poisson process, which describes the distribution of the number of events in one unit of time. This distribution is parameterized by a single rate and has mode zero, implying that the highest probability mass for events to happen is attributed to the earliest times. To describe biological processes, the exponential distribution is not always natural. For example, if the immune system has not encountered a pathogen before, it most likely responds to a viral infection after a few days, rather than immediately. In this paper, we generalize our recently proposed hypoexponential continuous time Bayesian networks, by allowing any number of hypoexponential variables, i.e., variables having a hypoexponential time duration distribution. In addition, we propose and compare two learning methods to estimate parameters for the generalized models. Finally, the practical value of the generalized models is demonstrated by means of a realistic medical problem.


Ontologies are structured vocabularies for organising domain knowledge, and are widely used in biological and biomedical research. They frequently contain thousands of terms and are arranged hierarchically with numerous non-hierarchical associations between terms. Ontology users and developers need to understand combinations of associations that are distributed across the hierarchy—a task which is not well supported by existing tools.
This thesis presents a new approach for interactive visualisation of associations within ontologies. It employs visual compression techniques and novel visual representations to facilitate effective ontology exploration and analysis. These techniques are implemented in the web-based system OntoPlot.


Multiple myeloma (MM) is a model for using in vitro and in vivo models of the tumor in its bone marrow (BM) microenvironment to target tumor cells, tumor-host interactions, and the BM milieu in novel therapeutics. To date proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), histone deacetylase (HDAC) inhibitors, and monoclonal antibodies (MoAbs) have translated from the bench to the bedside and FDA approval, extending the survival of patients 3- to 4-fold. Further progress is advancing in novel strategies to target protein homeostasis, novel immune therapies, and treatments targeting genomic anomalies. PIs trigger apoptosis in MM cells, modulate adhesion molecule expression on tumor and BM cells, and regulate cytokine secretion in the BM milieu. They also promote osteoclast apoptosis and promote new bone formation. Ubiquitin proteasome receptor inhibitor and ubiquitylating agent inhibitors target the ubiquitin proteasome pathway upstream of the proteasome and can overcome PI resistance. HDAC6 selective inhibitors block aggresomal protein degradation and synergize with PIs. IMiDs bind and activate cereblon ubiquitin 3 ligase activity, with degradation of IZF1/3 in MM cells. Excitingly, prototype degronimids bind to ubiquitin ligase complexes including cereblon, VHL, or MDM2, as well as bind and selectively target substrates for degradation. Multiple immune therapies are promising in MM. IMiDs activate T, NK, and NK-T cells and target regulatory T cells, at least in part related to degradation of alios/ikaros and thereby stimulating IL-2 transcription and secretion. IMiDS also bind a novel substrate p-53 related protein kinase (PRPK) and mediate cereblon-independent MM cytotoxicity. MoAbs targeting SLAMF7 and CD38 have moved rapidly from the bench to the bedside, with enhanced activity in combination with IMiDs or PIs. B-cell maturation antigen (BCMA) is a selective plasma cell antigen currently targeted with immunotoxin and bispecific antibodies, as well as by targeting its ligands BAFF and APRIL to downregulate growth and survival signaling. Checkpoint inhibitors are expressed on MM cells, as well as immune effector cells and accessory cells (myeloid-derived suppressor cells and plasmacytoid dendritic cells), which promote MM cell growth and drug resistance. Importantly, checkpoint inhibitors can overcome the effect of these accessory cells and trigger autologous cytotoxicity of patient MM cells. Moreover, IMiDs can enhance checkpoint inhibitor-induced cytotoxicity. Vaccination of patients with smoldering MM with peptide-based vaccines can trigger autologous anti-MM immunity, which is enhanced by IMiDs and shifted to a central memory phenotype by HDAC 6 inhibitor. Finally, BCMA CART cell therapies are achieving complete responses even in MM refractory to all other therapies. Combinations of these immune approaches offer the most promise. Finally, MM is very genetically heterogeneous, with ongoing DNA damage. RAS mutations are most common, with transient responses to MEK/ERK inhibitor therapy. Patients with t(11:14) MM and overexpression of BCL-2 can respond to venetoclax. Ongoing efforts are presently delineating mechanisms underlying the extensive constitutive and ongoing DNA damage, including homologous recombination, APEX nuclease activity, pan-nuclease activity, and APOBEC activity, in order to develop selective inhibitors. Other strategies target the consequences of the genetic heterogeneity, such as targeting STK4 activity to restore p73-mediated apoptotic signaling in MM with decreased YAP1 copy number. Additionally, MM with MYC amplification has high levels of replicative stress and reactive oxygen species (ROS); ATR inhibitors to block replicative stress response in combination with agents to increase ROS trigger synergistic MM cytotoxicity. Finally, targeting fast-forward loops or regulatory loops in MM, such as KDM3A-KLF2-IRF4 axis, offers great promise to target both the tumor and its microenvironment. Citation Format: Kenneth Anderson. Novel therapeutic targets in multiple myeloma [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; Sao Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr IA13.


Abstract Objective: To review the evidence on diet and nutrition relating to osteoporosis and provide recommendations for preventing osteoporosis, in particular, osteopototic fracture. Approach: Firstly, to review the definition, diagnosis and epidemiology of osteoporosis, to discuss the difficulties in using bone mineral density to define osteoporosis risk in a world-wide context and to propose that fragility fracture should be considered as the disease endpoint. Secondly, to provide an overview of the scientific data, the strengths and weaknesses of the evidence and the conceptual difficulties in interpreting studies linking diet, nutrition and osteoporosis. The following were considered: calcium, vitamin D, phosphorus, magnesium, protein and fluorine. Other potential dietary influences on bone health were also discussed, including vitamins, trace elements, electrolytes, acid–base balance, phyto-oestrogens, vegetarianism and lactose intolerance. Conclusions: There is insufficient knowledge linking bone mineral status, growth rates or bone turnover in children and adolescents to long-term benefits in old age for these indices to be used as markers of osteoporotic disease risk. For adults, the evidence of a link between intakes of any dietary component and fracture risk is not sufficiently secure to make firm recommendations, with the exception of calcium and vitamin D. For other aspects of the diet, accumulating evidence suggests that current healthy-eating advice to decrease sodium intake, to increase potassium intake, and to consume more fresh fruits and vegetables is unlikely to be detrimental to bone health and may be beneficial.


rehabilitation (PR) management of patients with chronic obstructive pulmonary disease (COPD). The 6-minute stepper test (6MST) is a new, well-tolerated, reproducible exercise test, which can be performed without any spatial constraints. Objective: The aim of this study was to compare the results of the 6MST to those obtained during a 6-minute walk test (6MWT) and cardiopulmonary exercise testing (CPET) in a cohort of COPD patients. Methods: Ninety-one COPD patients managed by outpatient PR and assessed by 6MST, 6MWT, and CPET were retrospectively included in this study. Correlations between the number of steps on the 6MST, the distance covered on the 6MWT, oxygen consumption, and power at the ventilatory threshold and at maximum effort during CPET were analyzed before starting PR, and the improvement on the 6MST and 6MWT was compared after PR. Results: The number of steps on the 6MST was significantly correlated with the distance covered on the 6MWT ( r = 0.56; P , 0.0001), the power at maximum effort ( r = 0.46; P , 0.0001), and oxygen consumption at maximum effort ( r = 0.39; P , 0.005). Performances on the 6MST and 6MWT were significantly improved after PR (570 vs 488 steps, P = 0.001 and 448 vs 406 m, respectively; P , 0.0001). Improvements of the 6MST and 6MWT after PR were significantly correlated ( r = 0.34; P = 0.03). Conclusion: The results of this study show that the 6MST is a valid test to evaluate exercise tolerance in COPD patients. The use of this test in clinical practice appears to be particularly relevant for the assessment of patients managed by home PR.


Hyperspectral images of high spatial and spectral resolutions are employed to perform the challenging task of

brain tissue characterization and subsequent segmentation for visualization of in-vivo images. Each pixel is

high-dimensional spectrum. Working on the hypothesis of pure-pixels on account of high spectral resolution,

we perform unsupervised clustering by hierarchical non-negative matrix factorization to identify the pure-pixel

spectral signatures of blood, brain tissues, tumor and other materials. This subspace clustering was

further used to train a random forest for subsequent classification of test set images constituent of in-vivo and

ex-vivo images. Unsupervised hierarchical clustering helps visualize tissue structure in in-vivo test images

and provides a inter-operative tool for surgeons. Furthermore the study also provide a preliminary study of the

classification and sources of errors in the classification process.


The ILETC team collectively set out to define the notion of teacher mind frames through a literature-based reflection about the issues central to our project. The aim was to map out a common research landscape that the large multidisiplinary research team could navigate across, as well as to frame the study and provide a scope to respond to the project's key research question


Endophytic actinomycetes encompass bacterial groups that are well known for the production of a diverse range of secondary metabolites, including various antibiotics, antitumor, immunosuppressive agents, plant growth hormones, and have capacity of survive inside of plants tissues. Vochysia divergens is a Brazilian medicinal plant common isolated in the Pantanal region, and was focus of many researches, but the community endophytic remains unknown. Therefore, the goals of the present work were to carry out an initial assessment of antimicrobial, antitumor and antioxidant activities of crude extract produced by endophytic actinomycetes isolated from Vochysia divergens. Using 16S sequences, 10 isolates were classified as Microbispora sp. and two isolates were classified as Streptomyces sampsonii. The other two isolates were identified as Micromonospora sp. and are apparently undescribed species. The isolates were able to produce secondary metabolites with antioxidant activity, antitumor activity against of Glioblastoma cell and antimicrobial activity against bacteria Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Methicillin-Resistant Staphylococcus aureus and the yeast Candida albicans. Taking into consideration the lack of effective medicaments for the treatment of Glioblastoma multiforme, and the increasing number of bacterial strains expressing resistance, the basic research using microorganisms from unexplored environmental showed can be an alternative to discover new secondary metabolites to treat these diseases.


These key questions so eloquently put by Dick also underpin the aims of 'Evil and Human Wickedness.' Rob uses similar words in his words on themain aim of the project: "I was - and remain - convinced that the problems of evil are inseparably and intimately tied to the problems of what it is to behuman."
4
The project had, and still has, three mains aims. Firstly, to start adiscourse on the nature of evil and human wickedness, questions which arerelevant to our very being-in-the world. Secondly in order to do this, it isnecessary to open up a dialogue across disciplines and beyond our own areasof interest and/or specialism in order to bring a wider understanding to suchcrucial issues beyond personal interpretations and pre-existing intellectualinvestment. Lastly, while we may not come up with answers to questionssurrounding the continuing problem of evil and human wickedness in theworld, it is necessary to wrestle with the question of evil in its manifoldforms, as this is not a mere intellectual exercise but a personal expedition intothe very core of humanity that calls upon us personally wrestle with "our ownexperiences and feelings about events and actions.


ABSTRACT The denial that racism operates against Muslims qua Muslims has permeated public and media discourse of late. Intellectuals, commentators and legislators from across the political spectrum have explicitly rationalized this position by distinguishing involuntary racial identities from voluntary religious identities. Meer explores the nature of Muslim identity vis-à-vis the involuntary and voluntary dichotomy before examining the consequences of recognizing some 'racial' identities in anti-discrimination formulas while ignoring others. This is followed by a short case study of some of the 'commonsense' arguments about race and religion that surrounded the proposed incitement to religious hatred legislation in Britain. The findings suggest that Muslims in Britain are disadvantaged by the operation of a 'normative grammar' of race that materially (in terms of legal instruments) and discursively (in terms of public and media comment) treats their racialization with less seriousness than it does that of other minorities.


Simple economic principles tell us that investment begets investment and wealth creates wealth. Investment of money alone, however, is seldom enough to trigger this virtuous cycle, time, effort and substantial planning are also critical elements. This working paper captures the story of transformation of Manipur's electricity distribution sector which has laid the foundation for a slow but sure transformation of a state that has seen more than its share of troubled times. This paper is about a World Bank-supported Government of Manipur's initiative to improve and institutionalize efficient commercial, Operation and Maintenance (O&M), project-related systems and processes, institutional strengthening and creation of a robust review and monitoring mechanism for the electricity distribution sector. The result is that Manipur is, gradually but steadily, moving forward on the road to socioeconomic development.


Nefrologia 2014;34(3):413-24 423 interstitial scarring was also noted. On immunolourescence (IF), there was diffuse, bright (3+, on a scale of 0 to 3+) positivity of IgM in the mesangium and peripheral capillary loops, accompanied by C3 and C1q in similar location (Figure 2). IgG and IgA were negative. A diagnosis of IgMN was rendered and lupus serology and serum antineutrophil cytoplasmic antibodies (ANCAs) were advised, which returned negative.


A new nonlinear filtering and prediction (NFP) algorithm with input estimation is proposed for maneuvering target tracking. In the proposed method, the acceleration level is determined by a decision process, where a least squares (LS) estimator plays a major role in detecting target maneuvering within a sliding window. We first illustrate that the optimal solution to minimize the mean squared error (MSE) must consider a trade-off between the bias and error variance. For the application of target tracking, we then derive the MSE of target positions in a closed form by using orthogonal space decompositions. Then we discuss the NFP estimator, and evaluate how well the approach potentially works in the case of a set of given system parameters. Comparing with the traditional unbiased minimum variance filter (UMVF), Kalman filter, and interactive multiple model (IMM) algorithms, numerical results show that the newly proposed NFP method performs comparable or better in all scenarios with significantly less computational requirements.


This case study charts the progress of a two-year programme to build a coaching culture at a small Australian multinational organisation. The intervention consisted of executive coaching and coaching skills workshops aimed principally at potential successors to the senior leadership team. Over the course of the programme the organisation went through many changes, including an organisational restructure and a change in CEO. The outcome of the intervention is discussed with reference to previously published models for implementing a coaching culture and to work on complex adaptive systems.


Set in May 2008, this case reflects the separate perspectives of chief executive officers Tom Eliot and Bill Flinder as they approach the negotiations of RSE International Corporation to acquire Flinder Valves and Controls Inc. The task for the student is to complete a valuation analysis of the target and buyer and to negotiate a price and exchange ratio with the counterparty. The intent of the case design is for students to be organized into teams and assigned to play the part of either Flinder Valves or RSE International in the negotiation. The case provides supplementary private information for each side of the transaction. Therefore, a unique element of the case is negotiating the terms of acquisition in an environment of asymmetric information. The case is relatively simple and provides a first exercise in the negotiation of an acquisition. It could also be taught in the usual case-discussion fashion instead of the intended joint-negotiation exercise.


Considerable controversy exists as to the timing of the important Mississippian carbonate-hosted Irish-type Zn + Pb ± Ba ± Ag deposits. The Silvermines deposits have been defined as an end member of this style in that they have been interpreted to display textures indicative of sea-floor deposition. One of the strongest arguments in favor of this interpretation was the report of a hydrothermal vent field, including pyritic chimneys in the Ballynoe open-pit barite deposit. This paper adds to that body of evidence by describing a hydrothermal vent fauna from the same vent field, consisting of a delicately pyritized worm tube hosted by massive pyrite and hematized filaments of apparent microbial origin. The worm tube is remarkably similar to fossil worm tubes from modern and ancient volcanic-hosted massive sulfide deposits, and the filamentous microfossils have similarities to modern Fe-oxidizing bacteria. We have found no correlation between the worm tube and normal Mississippian fossils such as crinoids, whose replacement by pyrite in the immediately underlying Ballynoe footwall destroys original morphology. The sulfur isotope composition of the worm tube and host pyrite is essentially identical to that of the vent field pyrite and the main sulfide ore stage of Silvermines sulfides, all having a mean value about –20 per mil, indicating an open-system bacteriogenic sulfide source. These discoveries provide additional evidence for the exhalative nature of parts of the Silvermines orebodies, and imply that mineralization had begun in the Irish ore field by the late Tournaisian (~352 Ma).


Advanced Topics in Signal Processing: Eds. J. S. LIM and A. V. OPPENHEIM (Prentice-Hall, 1988,518 pp., £48.15) This volume is meant to be used by those who are already familiar with the fundamentals of digital signal processing and who wish to pursue advanced topics further. The book covers 8 advanced topics including parametric signal modelling, multirate signal processing, adaptive signal processing and two-dimensional signal processing. Each of the advanced topics is written by an expert in that field and kept in a separate self-contained chapter. Thankfully, the notation has been kept consistent and the different chapters suitably crossreferenced. The price of this book, although seemingly high, is quite average for a Prentice-Hall signal processing hardback. B.P.OODIT Department of Electrical Engineering and Electronics, UMIST


The main objective of this study was to investigate and compare the mechanical properties and processability of single-filler and hybrid poly(vinyl chloride) (PVC) composites. Calcium carbonate (CaCO3) was used in this study to improve the impact strength of PVC while talc was used to improve stiffness. Filler was added into PVC at a constant loading level of 30phr. SM90 showed the most optimum properties in terms of impact strength and flexural modulus among all grades of CaCO3 selected for hybrid study. Tests specimens were prepared by using dry blending, two roll milling and compression moulding processes. Flexural, impact and tensile tests were then performed to determine and compare the effect of fillers on mechanical properties of PVC composites. Talc filled PVC composite showed the highest flexural modulus but the lowest impact strength. The impact strength of hybrid PVC composites gradually increased with increasing SM90 content, but the flexural modulus showed an opposite behaviour. The flexural strength and impact strength were the highest among the hybrids when the talc/SM90 weight ratio was 20:10. The distribution and dispersion of the fillers in PVC matrix were observed by using SEM. The well dispersion and interfacial adhesion of SM90 and talc particles in PVC matrix had contributed and helped in improving the stiffness and the impact strength of PVC composite. The fusion time of hybrid talc/SM90 filled PVC composite gradually increased as the talc content was gradually replaced by SM90. However, the hybrid (10phr talc: 20phr SM90) filled PVC composite showed the longest fusion time among all PVC composites. TGA, DSC and HDT tests were also carried out to investigate the thermal properties of PVC composites. The incorporation of talc and CaCO3 were found to improve the thermal stability and rigidity of PVC composites.


SUMMARY: The species Pseudomonas aeruginosa is defined more precisely, and a method is presented whereby apyocyanogenic strains of this species can be correctly identified. This method depends upon the correlated characteristics: (1) ability to grow at 41° ± 1; (2) ability to oxidize potassium gluconate, in shaken culture, to a reducing compound presumed to be potassium 2-ketogluconate; (3) production of slime in static culture in a medium containing potassium gluconate as the principal carbon source.
All strains of P. aeruginosa tested, regardless of their pigment-forming capacity or their stage of growth, could be converted to a type of growth characterized by profuse sliminess in liquid potassium gluconate medium.
Detection of pyocyanogenic capacity is shown to be equally reliable in Gessard's glycerol peptone agar and in Burton's defined medium when negative results in one or the other medium are rechecked in both, and when the observation period in Burton's medium is lengthened.


A 53-year-old man presented with sudden posterior chest pain without any preceding causative events. He had no significant medical history, including conditions requiring antithrombotic medication. His consciousness was clear, blood pressure was 110/80 mmHg, heart rate was 70 beats per minute (bpm), respiratory rate was 14 per minute, and SpO2 was 98% in room air.


Service relations are not systematically fluid, and resistance is sometimes encountered in cases of non-take-up. The service relation model fails to take this into account. Therefore, as service agents' work consists in dealing with users' relations not only with themselves, but also with the offer, the analysis of non-take-up of rights and services requires a specific analytical model. This model would need to take users into account along with their relations to the offer and the normative content of that offer, over and above its delivery. In this respect, the social relation to the service model is more appropriate.


BACKGROUND
Lung transplantation for end-stage pulmonary disease is an established procedure and the number of transplantations is increasing worldwide even in developing countries. Usually donor lungs are transported in an inflated state and the bronchi are closed with a stapler device.

CASE REPORT
We present a technique that avoids costly stapler devices and is even less time consuming than reloading the staplers. After both lungs are inflated the separation of the two main bronchi is facilitated by using sterile umbilical cord clamps for the bronchus closure. We did not experience any air leaks and since the bronchi are resected prior to implantation there is always enough space to place the clamps.

CONCLUSIONS
The umbilical cord clamp technique reduces the explantation costs for lung retrievals significantly. The technique is less time consuming and offers equal safety compared to stapler devices.


Background Lymph node stromal cells (LNSC) play a crucial role in shaping the immune response and maintaining peripheral tolerance. We developed an experimental model for studying the functional capacities of human LNSC during the earliest phases of RA and compared their cellular and molecular characteristics to LNSC from healthy volunteers. Methods ACPA+ RA patients (n=24), ACPA+ RA-risk individuals (n=23) and seronegative healthy controls (n=14;HC) underwent ultrasound-guided inguinal lymph node biopsy. Human LNSCs were isolated and expanded in vitro for cellular (flow cytometry), molecular (methylome, transcriptome and microRNA) and functional (contraction) analyses. Results RNA sequencing was performed on LNSC of HC (n=5), ACPA+ RA-risk individuals (n=6) and ACPA+ RA patients (n=4). Of interest, LNSC from ACPA+ RA-risk individuals and ACPA+ RA patients were more similar to each other compared with HC. Pathway analysis of commonly increased genes in RA (-risk) LNSC showed, among others, significant enrichment of pathways affecting actin cytoskeleton, focal adhesion and cell junction. DNA methylation (Illumina HumanMethylation450 array) analyses revealed 459 differentially methylated CpG sites (DMS) in LNSC from ACPA+ RA patients (n=5) versus HC (n=4), 504 DMS between ACPA+ RA-risk individuals (n=3) versus HC and 665 DMS when comparing RA patients with RA-risk individuals (delta β-value >0.1, p<0.05). 34 DMS were different in both RA and RA-risk LNSC compared to healthy LNSC. 80% of these DMS were significantly hypomethylated and associated with antigen processing and presentation (HLA-DRB1), immune response and regulation of actin cytoskeleton. Accordingly, in a gel contraction assay LNSC from ACPA+ RA-risk individuals and RA patients showed impaired collagen contraction compared to healthy LNSC. Healthy LNSC (n=5) covered 26.5% +/-2.5 of the well, while RA-risk (n=4) and RA (n=5) LNSC only covered 33.9% +/-5.9 and 30.6% +/-6.5. Conclusions This data point towards alterations in the cytoskeleton and antigen-processing and presentation in LNSC from ACPA+ RA-risk individuals and RA patients. Further studies are required to investigate the influence of this LNSC abnormality on immune responses. Disclosure of Interest C. Ospelt: None declared, E. Karouzakis: None declared, J. Hähnlein: None declared, J. Semmelink: None declared, R. Gay: None declared, P. Tak Employee of: GSK, D. Gerlag Employee of: GSK, S. Gay: None declared, L. van Baarsen: None declared


One of the essential components of a virtual reality surgical simulation is deformation. Deformations in computer graphics and surgical simulations are commonly modeled with three different approaches e.g. geometry based methods, Finite Element method(FEM), and Mass-spring Method (MSM). The geometry based methods are quite fast and visually appealing. Late two methods take the physics of deformation into consideration. Even though the FEM results in more physically realistic deformations, a significant drawback of this method is its expensive computation cost and vulnerability to surgical procedures such as incision. However,MSM is relatively computationally inexpensive.Because of the real-time physics based behavior of MSM, it is widely accepted by surgical simulation community. This study summarizes deformation simulation methods and their pros and cons for surgical simulations. Moreover, because of wide usage of the MSM, optimized data structures for MSM are provided and analyzed under different deformation settings.


We propose to integrate performance analysis in the early phases of the model-driven development process for Software Product Lines (SPL). We start with a multi-view UML model of the core family assets representing the commonality and variability between different products, which we call the SPL model. We add another perspective to the SPL model, annotating it with generic performance specifications expressed in the standard UML profile MARTE, recently adopted by OMG. The runtime performance of a product is affected by factors contained in the UML model of the product (derived from the SPL model), but also by external factors depending on the implementation and execution environments. The external factors not contained in the SPL model need to be eventually represented in the performance model. In order to do so, we propose to represent the variability space of different possible implementation and execution environments through a so called "performance completion (PC) feature model". These PC features are mapped to MARTE performance-related stereotypes and attributes attached to the SPL model elements. A first model transformation realized in the Atlas Transformation Language (ATL) derives the UML model of a specific product with concrete MARTE annotations from the SPL model. A second transformation generates a Layered Queueing Network (LQN) performance model for the given product by applying an existing transformation named PUMA, developed in previous work. The proposed technique is illustrated with an e-commerce case study. A LQN model is derived for a product and the impact of different levels of secure communication channels on its performance is analyzed by using the LQN model.


The aim of this work is to enable the construction of artificial conversational agents capable of working in a multi-party setting. By an artificial conversational agent we mean a software agent (possibly with embodiment, personality etc.), capable of engaging in conversation with other conversational agents (human or artificial). By a multi-party setting we mean that more than two agents are engaged in the communication or dialogue. Components designed for two-party dialogue management including sequencing and turn management cannot, in general, handle multi-party dialogue phenomena, such as keeping track of the obligations regarding turn management and the rights and obligations to address an issue. We present an SCXML implementation of Issue-Based Dialogue Management, scaled up to handle more than two participants. The QUD-based dialogue manager makes a distinction between distributive questions (to be answered individually by each addressee) and collective questions (to be answered by the addressees collectively), in order to provide the right kind of grounding behaviour and in order to manage correctly the obligations put on the participants of the dialogue. The dialogue manager also features an SCXML implementation of the SSJ turn management model. We find that it is possible to scale up the Issue-Based Dialogue Management model from twoparty to multi-party dialogues, given that distributive and collective readings of questions can be identified.


Propped hydraulic fractures have enabled economic hydrocarbon production from organic rich shales. Laboratory testing of proppants can help in systematic evaluation of different factors that can affect proppant performance. This study is focused on long-term conductivity measurements of proppant-packs at simulated reservoir pressure and temperature conditions. Mechanisms like proppant crushing, embedment, and diagenesis are investigated.
 Testing was done using a conductivity cell made of Hastelloy; allowing simultaneous measurement of fracture compaction and permeability. The proppant filled fracture (concentration: 0.75-3 lb/ft2) is subjected to axial load (5000 psi) to simulate closure stress. Brine is flowed through the pack at a constant rate (3 ml/min) at elevated temperature (250° F) over an extended duration of time (from 10-60 days). 20/40 and 60/100 mesh Ottawa sand were used in this study. The proppant-pack performance is evaluated between shale platens fabricated from Eagle Ford rock (58% clay by wt.; Nanoindentation Young's modulus - 16 GPa).
 Experiments on the 20/40 and 60/100 Ottawa sand (1.5 lb/ft2 proppant concentration) at elevated pressure (5000 psi) and temperature (250° F), spanning 10 days demonstrate that proppant size strongly impacts proppant performance. The proppant-pack permeability for 60/100 sand drops dramatically within a few hours. The 20/40 proppant permeability is double the permeability of 60/100 sand even after 10 days of testing. Approximately 60% compaction is observed over the test duration, with 28% contribution from proppant crushing and rearrangement, and 32% contribution from embedment. Particle size analysis of proppant grains and SEM images verify proppant crushing, fines migration and embedment as dominant damage mechanisms. Proppant embedment and crushing are observed to be dependent on the shales being tested.
 Fracturing jobs involve maintaining a basic pH environment for optimal performance of fluid additives for better proppant placement via control on viscosity. A second study was conducted to compare performance on similar Eagle Ford shale by altering the fluid chemistry (pH ~ 10.5) to understand the impact on permeability and compaction over time. Over a duration of 20 days, the permeability dropped from 120 darcy to 200 md. After 8 days, the pH:10 brine permeability was 10 times lower than pH:7 brine permeability. After 18 days, the fracture width reduced by 90%, indicating a creep behavior. High silica content (>20 ppm) was observed in the outlet brine. The proppant and rock surface were studied under SEM to investigate the role of secondary mineral growth during the drastic reduction of permeability.
 This study is focused on understanding fracture conductivity under as realistic near in-situ experimental conditions. Testing between shale platens at reservoir temperature and pressure conditions is more representative of subsurface environment. Dynamic measurements in the current study were conducted for long duration (spanning 10-30 days) using brine. This allows the study of effects of mechanical and chemical degradation of fracture conductivity, which has been used to separate the effects of crushing and embedment. Our results demonstrate that the fracture conductivity is dependent on proppant size and pH of the flowing solution.


Abstract Objective numerical techniques are applied in analyzing constant altitude aircraft measurements obtained from coordinated research flights in thunderstorm inflow regions. The approach combines meteorological and flight track data from dual or single aircraft missions in a common frame of reference and transforms the observations from original analogue format to horizontal two-dimensional Cartesian coordinates. Operational procedures guiding the data collection, intercomparison techniques for refining instrument calibrations and corrections for aircraft navigation errors are all considered. Results of the interpolations are judged in the context of the storms' associated radar echo features. Primary applications include calculation of water vapor influx in cloud base updrafts. Evidence indicates that the fullest exploitation of the inflow mapping will come through combining kinematic fields observed concurrently by aircraft and multiple Doppler radars.


EAEC, are important diarrhoeal pathogens, being the most common cause of watery, persistent and
inflammatory diarrhoea (Okeke &Nataro, 2001). Several neurotransmitters such as 5-HT and
substance P have been implicated in the pathogenesis of diarrhoea induced by cholera toxin and clostridium difficile toxin A (Farthing 2000). The aim of the present study was to investigate the effect of EAEC on 5-HT, carbachol and EFS-induced contraction in the rat ileum.


The recent development of low cost wireless sensors enables water monitoring through dense wireless sensor networks (WSN). Sensor nodes are battery powered devices, and hence their limited energy resources have to be optimally managed. The latest advancements in compressive sensing (CS) provide ample promise to increase WSNs lifetime by limiting the amount of measurements that have to be collected. Additional energy savings can be achieved through CS-based scheduling schemes that activate only a limited number of sensors to sense and transmit their measurements, whereas the rest are turned off. The ultimate objective is to maximize network lifetime without sacrificing network connectivity and monitoring performance. This problem can be approximated by an energy balancing approach that consists of multiple simpler subproblems, each of which corresponds to a specific time period. Then, the sensors that should be activated within a given period can be optimally derived through dynamic programming. The complexity of the proposed CS-based scheduling scheme is characterized and numerical evaluation reveals that it achieves comparable monitoring performance by activating only a fraction of the sensors.


The aim of this study was to compare the frequency and intensity of burnout among nurses with high humor scores (n=30) and those with low humor scores (n=30) in Qazvin City, 2011. Subjects were selected by cluster random sampling and targeted sampling methods. The measurement tools included two questionnaires: the Sense of Humor Questionnaire (SHQ) and the Maslach Burnout Inventory (MBI). Data were analyzed by descriptive statistics and analytical statistics using ANOVA. Frequency and intensity of burnout was lower in nurses with high humor scores compared to nurses with low humor scores.


At present we see only one basic approach being considered by implementors and standards organizations for provisioning of dynamic protected lightpath services that make efficient use of shared protection capacity. This is the paradigm of a primary working path protected end-to-end by a disjoint backup path using shared spare capacity. Sharing is arranged among the backup paths associated with other primary paths that are failure-disjoint from the current primary path. This approach called shared backup path protection (SBPP) has many advantages but also provides a great deal of network state information to be available and current in every node. It also makes the arrangement of protection a per-connection task, rather than user-selectable service option supported by the network itself. We propose an alternative paradigm for consideration, partly summed up as provisioning over protected capacity rather than provisioning protection. Under a given distribution of spare capacity, locally acting protection or restoration schemes create an "envelope" of protected working channels. Dynamic provisioning within this envelope is simplified to a shortest path routing problem and (depending on the mode of operation) requires little or no dissemination of state changes on a per-connection basis. We explain how existing "static" capacity design methods can be adopted to the dimensioning of such a working capacity envelope and the envelope dimensions further adapted online to track evolution of the overall pattern of random demand. An important property is that nothing needs to be done to arrange protection for services on the per-connection timescale other than routing the service itself. Arbitrarily fast-paced demand arrivals and departures can be accommodated within a static distribution of spare capacity. Adjustments to the envelope itself are required only on the timescale on which the statistical parameters of the random demand changes. This may provide an inherently more scalable, less database-dependent, and higher-availability alternative than SBPP, or at least an additional service modality that can be offered to customers.


Genetic linkage analysis is a challenging application which requires Bayesian networks consisting of thousands of vertices. Consequently, computing the likelihood of data, which is needed for learning linkage parameters, using exact inference procedures calls for an extremely efficient implementation that carefully optimizes the order of conditioning and summation operations. In this paper we present the use of stochastic greedy algorithms for optimizing this order. Our algorithm has been incorporated into the newest version of superlink, which is currently the fastest genetic linkage program for exact likelihood computations in general pedigrees. We demonstrate an order of magnitude improvement in run times of likelihood computations using our new optimization algorithm, and hence enlarge the class of problems that can be handled effectively by exact computations.


The study of human-animal relationships in their myriad forms has the potential to answer some of
the most fundamental questions relating to human behaviour and cultural identity. It is therefore
surprising that zooarchaeology has rarely been utilised to its full potential to inform on the
significant changes that took place over the course of the Anglo-Saxon period, with analysis seldom
moving beyond socio-economic interpretations of animal husbandry. The large, well-dated
zooarchaeological assemblage from Anglo-Saxon Lyminge, Kent, offers an exceptional opportunity to
examine how human-animal relationships were shaped and reconfigured by key historical processes
encapsulated by a 500-year occupation sequence. Lyminge is a high-status Anglo-Saxon settlement
of international importance, incorporating a fifth – sixth century settlement, which developed into a
seventh century hall-complex, and finally evolved into a spatially distinct documented eighth – ninth
century pre-Viking monastery (Thomas 2017).
This thesis presents the results of the zooarchaeological analysis and interpretation of the faunal
assemblage from Lyminge, adopting an integrated multi-disciplinarily approach which includes the
results of a small-scale isotope study of the faunal remains. Thesis data is contextualised within a
broader synthesis of archaeological and zooarchaeological data from contemporary sites to assess
how shifts in animal husbandry, attitudes to the wild, treatment of companion animals and the
consumption of food, reflect changing world-views on both a site-based and regional scale.
The results of this analysis indicate that there were distinct diachronic trends in species
representation and, in the case of domesticated animals, management strategies, that coincide with
Lyminge's transformation from a pre-Christian royal vill into an affluent monastic community. These
transformations are particularly evident in the shift from the consumption of large quantities of pigs
in the fifth – seventh century to the consumption of high numbers of chicken in the eighth – ninth
century, a change that is accompanied by more intensive sheep husbandry and a new focus on
arable agriculture. Such dramatic shifts in dietary patterns identified through innovative
zooarchaeological research reflect wider changes in cultural practices and religious affiliations of the
Kentish elite at a pivotal moment in the formation of Christian kingdoms throughout Anglo-Saxon
England.


"Unquestionably Africa's most versatile writer and arguably one of her finest" (New York Times Book Review) These hilarious and vicious two plays examine the corruption of Nigerian society through a study of the rise and fall of one of its self-made charismatic preachers."Wole Soyinka's Nobel Prize for Literature is a triumphant affirmation of the universality of this novelist, poet, film-maker and political activist." (Guardian)


The study assesses the cells in platelet-rich fibrin using advanced platelet-rich fibrin and standard platelet-rich fibrin protocol between two age groups. Platelet-rich fibrin (PRF) is a fibrin matrix in which various cells are trapped including platelets and growth factors. It was first developed by Choukron et al. in France in the year 2001, It is a second-generation platelet concentrate developed for use specifically in oral and maxillofacial surgery. It is known to have various regenerative and healing properties including tissue regeneration, revascularization, osteogenic properties, etc. making it ideal for wound healing. PRF can be classified into two types based on the centrifugation protocol as standard–platelet-rich fibrin (S-PRF) and advanced platelet-rich fibrin (A-PRF). This study required volunteers from two different age groups: younger age group between 18–25 years and older age group which was more than 50 years. Histological analysis reveals the following: Monocyte quantity is similar in both S-PRF and A-PRF. Neutrophils are comparatively higher in the above 50 age group. Lymphocytes (S-PRF) more in older than younger age groups. Cells more distributed in A-PRF and concentrated in S-PRF. Loose fibrin in S-PRF and dense fibrin in A-PRF. Although it was found that the older age group could prove to have better properties in PRF, the results are inconclusive due to the limited sample size. Further research is required to enable optimal scaffold formation to be tailored for specific clinical applications.


This note considers Tobin's average Q in a framework where firms finance investment by equities and debt. The determination of its long-run equilibrium value Q° is based on positing equality of the loan rate and, adjusted for a risk premium, the return on equities. Q° can thus be characterized as a ratio of two rates representing the somewhat modified interest costs and profits of the firms. The familiar benchmark value Q° = 1 obtains if another condition on the risk premium holds true, which may or may not be the case. An elementary numerical check demonstrates that possible deviations of Q° from unity are not overly dramatic.


To what extent does the Constitution commit the United States to comply with international law? The question is a critical one, with implications for both the stature of international law and the conduct of U.S. foreign affairs. The question is also one of degree. Few would argue that the Constitution invariably commits the United States to comply with international law. Most scholars, for example, agree that Congress has discretion to violate international law by statute. At the same time, few would argue that the Constitution leaves the United States free to disregard international law entirely. Scholars agree, for example, that self-executing treaties preempt conflicting state laws, forcing the states to comply with these treaties' terms. The critical question is where along the spectrum between commitment and discretion the constitutional position toward international law lies. This Article asserts that the position tends closer to national discretion to violate international law than constitutional commitment scholarship might suggest.Scholars who claim a constitutional commitment to international law make both broad and narrow claims. Some argue that the Constitution as a whole reflects a strong commitment to international law compliance. Others find that while the Constitution does not require the United States to comply, it does bind either or both of its political branches to international law compliance. Scholars assert, for example, that the Take Care Clause obligates the President to adhere to the two primary sources of international law: treaties and customary international law ("CIL"). Others contend that the Supremacy Clause obligates U.S. treatymakers to enter self-executing treaties — that is, treaties that are immediately enforceable in U.S. courts — to preempt state law and prior inconsistent federal statutes.Not all scholars who claim a constitutional commitment to international law proceed from historical premises, but many do. They invoke Founding-era history to support constitutional obligations to international law. Moreover, to the extent Founding-era history is a relevant guidepost in constitutional interpretation, Founding-era history is relevant to the validity of claims that have not relied on it. Founding-era history yields at least two bodies of evidence in support of a constitutional commitment to international law. First, the Founding era provides a wealth of statements by leading figures underscoring the importance of compliance with international law. These statements are consistent with theories of law, especially natural law, common to the Founders.Second, Founding-era history yields the oft-repeated narrative that the drafting and ratification of the Constitution were motivated, in significant part, by state violations of international law during the period of Confederation. This conventional narrative is true as far as it goes. Under the Articles of Confederation, the states unquestionably violated U.S. treaties, including the Treaty of Peace with Great Britain, causing serious foreign relations problems for the nation as a whole. Moreover, the Confederation Congress lacked power to mandate compliance with CIL, leaving the states to prosecute CIL violations. A desire to control state violations of treaties and to empower the national government to respond to CIL violations undoubtedly influenced the terms and ratification of the Constitution.Yet a strong constitutional commitment to comply with international law does not follow as a matter of logic or history. Logically, the narrative of concern for state violations and state power provides a motive to centralize power. But, centralizing power is different than, and does not require, restraining the power that is centralized. Thus, it is illogical, without more, to rely on the conventional narrative of state violation and state control to find a constitutional commitment to international law compliance.Nor does history bridge the gap. The oft-times unspoken assumption behind the conventional narrative is that under the Articles of Confederation the national government, unlike the states, was committed to international law but simply lacked the power to comply. The Constitution, it is believed, gave the national government the authority to follow through on its commitment to adhere to international law. This catechism has emerged, however, from scholars' unrelenting focus on state practice during Confederation. When the focus broadens to include the national government, the catechism collapses.The national government under the Articles of Confederation did not manifest consistent compliance with international law. Focusing for the first time on the national government's behavior toward international law during Confederation, this Article reveals that the Confederation government, like the states, violated international law. More specifically, the national government departed from the law of nations governing treaty ratification and engaged in self-interested interpretation, if not violation, of the handful of treaties the United States had entered.When it came time to create the Constitution, there was unquestionably concern for compliance with international law. The principal documents bearing on the Constitution's creation — the debates of the Constitutional Convention, Federalist Papers, and records of state ratification conventions — clearly reveal, consistent with the conventional narrative, a concern for state violations of international law. But no similar concern was expressed for the national government's departures from international law. Had there been such a concern, it might have led to an express constitutional mandate of national compliance. Rather than adopt such a mandate, the Constitution embraced structural reforms to facilitate adherence to international law. That is, the Constitution transferred foreign affairs powers from the states to the federal government and assigned the exercise of those powers to players and processes that could improve compliance with international law. The result is that just as federalist interests are generally protected today through lawmaking players and processes, compliance with international law appears to be secured through constitutional structure.This is not to say that there is no evidence to support a commitment to international law compliance by the federal government or a subset of its actors. The focus of this Article is on the core Founding-era evidence that has been cited to support (or that might bear on, even if not cited by particular scholars) constitutional commitment to international law compliance. As to that evidence, once one takes into account the national government's departures from international law during Confederation, Founding-era statements in support of international law compliance and the conventional narrative of state noncompliance take on a different hue. The broader history suggests that these statements reflect a general commitment to international law that may yield in the face of concrete national interests. Similarly, the lack of concern during the Constitution's creation for the Confederation government's violations of international law coupled with the Constitution's adoption of structural protections, rather than a substantive mandate, of international law compliance undermine claims of a strong constitutional commitment to international law compliance. The upshot is increased support for constitutional discretion to violate international law.This Article reaches this conclusion as follows. Part I surveys prominent scholarly arguments for constitutional commitment to international law, noting, in particular, reliance on Founding-era evidence, including the conventional narrative of state violation of international law during Confederation. Section II.A briefly demonstrates that the logic of the conventional narrative — which is the logic of collective action — does not compel constitutional commitment to international law, leaving space for an alternative thesis. Section II.B steps into that space to offer such a thesis. Section II.B departs from the conventional, state-focused narrative to reveal the as-yet-untold story of the national government's actions toward international law under the Articles of Confederation. This Section documents ways in which the Confederation Congress departed from the law of nations and bent treaties to national advantage. Part III explores the primary records of the Constitution's creation — the Constitutional Convention debates, Federalist Papers, and state ratification records — to reveal that the focus during the Constitution's formation was on state, not national, violation of international law. The Framers did not express concern for the Confederation government's departures from international law. Consistent with this lack of concern, the Constitution embraced not a substantive mandate to comply with international law, but structural reforms that could facilitate international law compliance.As a general matter, the national government's violation of international law during Confederation, the absence of concern for that violation during constitutional creation, and the Constitution's ultimate adoption of structural protections rather than an obvious substantive mandate of national compliance suggest that claims of a constitutional commitment to international law compliance are overstated. The takeaway is not that the United States or its agents should violate international law. Compliance may, in fact, be the best policy and what the Framers and ratifiers generally anticipated. However, the evidence developed in this Article lends support for national discretion to violate international law.


We consider low-distortion embeddings for subspaces under \emph{entrywise nonlinear transformations}. In particular we seek embeddings that preserve the norm of all vectors in a space $S = \{y: y = f(x)\text{ for }x \in Z\}$, where $Z$ is a $k$-dimensional subspace of $\mathbb{R}^n$ and $f(x)$ is a nonlinear activation function applied entrywise to $x$. When $f$ is the identity, and so $S$ is just a $k$-dimensional subspace, it is known that, with high probability, a random embedding into $O(k/\epsilon^2)$ dimensions preserves the norm of all $y \in S$ up to $(1\pm \epsilon)$ relative error. Such embeddings are known as \emph{subspace embeddings}, and have found widespread use in compressed sensing and approximation algorithms. We give the first low-distortion embeddings for a wide class of nonlinear functions $f$. In particular, we give additive $\epsilon$ error embeddings into $O(\frac{k\log (n/\epsilon)}{\epsilon^2})$ dimensions for a class of nonlinearities that includes the popular Sigmoid SoftPlus, and Gaussian functions. We strengthen this result to give relative error embeddings under some further restrictions, which are satisfied e.g., by the Tanh, SoftSign, Exponential Linear Unit, and many other `soft' step functions and rectifying units. Understanding embeddings for subspaces under nonlinear transformations is a key step towards extending random sketching and compressing sensing techniques for linear problems to nonlinear ones. We discuss example applications of our results to improved bounds for compressed sensing via generative neural networks.


Abstract. A 21-yr record is presented of surface mass balance measurements along the K-transect. The series covers the period 1990–2011. Data are available at eight sites along a transect over an altitude range of 380–1850 m at approximately 67° N in West Greenland. The surface mass balance gradient is on average 3.8 × 10−3 m w.e. m−1, and the mean equilibrium line altitude is 1553 m a.s.l. Only the lower three sites within 10 km of the margin up to an elevation of 700 m experience a significant increasing trend in the ablation over the entire period. Data are available at: doi:10.1594/PANGAEA.779181 .


Language samples from 10 adults using an augmentative and alternative communication (AAC) system were analyzed for gender differences in performance measures. Participants (5 female; 5 male) were matched on device, access method, software, experience, age, and education. Each participant was asked to describe the "cookie theft" picture from the Boston Diagnostic Aphasia Examination (BDAE; Goodglass & Kaplan, 1983). The language samples were analyzed on the following two dependent variables: frequency of Semantic Compaction™ language representation use and average communication rate. A dependent samples t-test and the equivalent non-parametric matched-pair Wilcoxon tests were conduced on both variables. The effect size and the power were also calculated and used to support the following results. There was not a significant difference in the Semantic Compaction™ dependent variable, however there was a large effect size (d=1.11). A power analysis indicated a sample size consisting of 9 pairs (4 more males and 4 more females) would increase the power to 82%. Further research with an increased sample size of 9 pairs of participants may provide more support for the current finding in relation to the use of Semantic Compaction™.No significant difference was found between the average communication rates of the genders; however the presence of a female outlier was concluded to influence these results. A dependent samples t-test was conducted on the data excluding the pair containing the outlier. The results of the dependent samples t-test indicated a significant difference between the genders in the average communication rates. Overall, for both dependent variables, the majority of males were higher on the performance measures than their paired female participants. These observations support a need for future research addressing gender differences in individuals who use AAC. Clinical implications suggest that future research is needed to determine if intervention strategies need to accommodate for differences between genders in their ability to effectively use their device to communicate as fast as they are able. Caution needs to be used when interpreting and applying these results to this population due to the limitations (i.e., small sample size and lack of control of extraneous variable) of the current study.


ABSTRACT Macrolide treatment failure in syphilis patients is associated with a single point mutation (either A2058G or A2059G) in both copies of the 23S rRNA gene in Treponema pallidum strains. The conventional method for the detection of both point mutations uses nested PCR combined with restriction enzyme digestions, which is laborious and time-consuming. We initially developed a TaqMan-based real-time duplex PCR assay for detection of the A2058G mutation, and upon discovery of the A2059G mutation, we modified the assay into a triplex format to simultaneously detect both mutations. The point mutations detected by the real-time triplex PCR were confirmed by pyrosequencing. A total of 129 specimens PCR positive for T. pallidum that were obtained from an azithromycin resistance surveillance study conducted in the United States were analyzed. Sixty-six (51.2%) of the 129 samples with the A2058G mutation were identified by both real-time PCR assays. Of the remaining 63 samples that were identified as having a macrolide-susceptible genotype by the duplex PCR assay, 17 (27%) were found to contain the A2059G mutation by the triplex PCR. The proportions of macrolide-susceptible versus -resistant genotypes harboring either the A2058G or the A2059G mutation among the T. pallidum strains were 35.6, 51.2, and 13.2%, respectively. None of the T. pallidum strains examined had both point mutations. The TaqMan-based real-time triplex PCR assay offers an alternative to conventional nested PCR and restriction fragment length polymorphism analyses for the rapid detection of both point mutations associated with macrolide resistance in T. pallidum.


We used density functional theory calculations to investigate the catalytic potential of Ag7Au6 alloy nanoclusters for the reduction of NO by CO. The mechanism comprises two main reaction stages: reduction of NO to generate N2O followed by deoxygenation of N2O by CO to form N2 and CO2. These N2 and CO2 products desorb easily from the active Ag7Au6 site, thereby avoiding catalyst poisoning. Potential energy surfaces of the doublet- and quartet-states were systematically elucidated. No spin crossing was found during the entire reaction and our results show that the reaction preferably follows the doublet state pathway. The main reaction pathways take place at Ag7Au6 cluster facet sites, rather than at edge sites. The crucial step involves Ag7Au6-catalysed reduction of NO to generate N2O; deoxygenation of NO via the CO-reaction pathway is kinetically more favorable than that in the absence of CO. The NO reduction to generate N2O is the rate determining step with an energy barrier of 175.2 kJ mol−1. Our results reveal that this catalysed reaction is both thermodynamically and kinetically favourable. We conclude that the Ag7Au6 nanocluster has potential as a highly active catalyst for conversion of CO and NO pollutants into non-harmful products under ambient conditions.


In a land of ice, great warriors search for glory. When a dragon threatens the people of the north, only one man can destroy the fearsome beast. Elsewhere, a mighty leader gathers a court of champions, including a noble warrior under a terrible curse. The Earth's creation is described; tales of the gods and evil Frost Giants are related; and the dark days of Ragnarok foretold. This is a journey into a realm of legend, where heroes from an ancient age do battle with savage monsters, and every man must live or die by the sword.


Isotopic studies of the Rb-Sr and U-Th-Pb systems in whole-rock samples and the U-Pb systematics for zircons document the existence of two late Arehean intrusive events in the Wind River Range. All of the systems examined indicate an age of ∼2,630 ± 20 m.y. for the Louis Lake batholith. Apparent ages for the Bears Ears pluton range from 2,504 ± 40 m.y. to 2,575 ± 50 m.y. The scatter in apparent ages for the Bears Ears pluton does not appear to be primarily the result of disturbance by postintrusive events, but it may be explained by an isotopically inhomogenous magma at the time of intrusion. Data for a few samples indicate that the Wind River Range was affected locally by a postmagmatic hydrothermal event that was approximately Tertiary in age. This event lowered δ 18 O values and disturbed parent-daughter relationships in most of the isotopic systems investigated, but it was recent enough that there is no demonstrable effect in the Pb-Pb system. The Bears Ears pluton has some chemical and petrologic features that are similar to those reported for the granites in the Granite Mountains to the east. These granites are spatially associated with low-temperature uranium deposits of Tertiary age and have been shown to have lost large amounts of uranium during the early to middle Tertiary. U-Pb systematics indicate, however, that the low to moderate uranium contents and highly variable Th/U values noted for the Bears Ears pluton are best interpreted as being primary features. If uranium was lost after magma generation, the loss most likely occurred at the time of intrusion. Such a loss could account for uraniferous Precambrian pegmatites southwest of the main part of the Range. The two intrusive units apparently were derived from different protoliths that were formed during early to middle Archean. Initial isotopic ratios and petrochemistry for the Louis Lake batholith are consistent with an early Archean trondhjemitic to tonalitic source. The protolith for the Bears Ears pluton must have been more evolved and somewhat younger. Inconsistencies as to the degree of evolution of this protolith, as inferred from isotopic and trace-element data, suggest that the protolith may have been subjected to high-grade meta-morphism that caused loss of Rb and U prior to generation of the magma.


All 24 cases of confirmed and evaluable Stage I favorable histology (FH) Wilms' tumor (WT) relapsing to date on the Third National Wilms' Tumor Study (NWTS‐3) were compared with 48 matched control subjects who had not relapsed for at least 2 years after diagnosis. Fifteen of the clinical and pathological variables studied, including patient age and tumor size, had no significant relationship to the outcome of this study. Four histologic features, all related to the degree of tumor extension within the "tumor‐kidney unit" proved to be significantly associated with relapse. These were (1) invasion of the tumor capsule, (2) presence of an "inflammatory pseudocapsule," (3) renal sinus invasion, and (4) tumor in intrarenal vessels. One or more of these features was present in 100% of relapsed cases (excluding one for which two variables were unevaluable), but occurred in only 46% of controls (P < 0.0002). Therefore, no relapses occurred in the NWTS‐3 when all four variables were negative. This result was confirmed by a review of all Stage I cases in the NWTS‐1 who had relapsed and who were treated by single‐agent chemotherapy. Again, no relapses occurred when all four factors were negative. These results demonstrate the feasibility of "microsubstaging" and could serve as a basis for future refinements of therapy for Stage I favorable histology Wilms' tumor.


During inflammation, the liver responds to pro-inflammatory signals by producing and secreting acute phase reactants (APR) involved in the inflammatory process. The notable increase in the level of these proteins is due to transcriptional induction that is jointly mediated by the pro-inflammatory cytokines IL-1β, TNFα and IL-6. Although critical to restoring homeostasis during infection or trauma, the hepatic response to these cytokines can be deleterious in pathologies involving chronic inflammation such as cancer. We set out to decipher how pro-inflammatory cytokines cooperate to elicit a transcriptional response in hepatocytes. We examined the transcriptome of primary mouse hepatocytes treated with different combinations of cytokines and found several gene expression patterns showing a complex cross-talk between cytokine signaling pathways. Specifically, we found that a dual treatment of IL-1β and IL-6 results in a synergistic expression of 164 genes, many of which are APR genes. TNFα had an effect similar to IL-1β, albeit weaker. A sequential rather than a combined treatment attenuated the synergistic effect, suggesting direct cooperation between the two cytokines in inducing transcription (as opposed to a cascade of transcription). Assaying enhancer activity by H3K27ac ChIP-seq revealed the dynamic nature of cytokine-responsive enhancers, with hundreds of enhancers changing their activity level following either treatment. Importantly, enhancers becoming more active upon dual IL-1/IL-6 treatment were enriched with binding sequences for STAT3, CEBP, AP1 and NFkB. Because IL-6 is the major pro-inflammatory cytokine and its transcriptional effects are mediated by the STAT3 transcription factor (TF), we assayed STAT3 binding patterns by ChIP-seq. As expected, STAT3 binding was elevated following IL-6 treatment genome-wide. Surprisingly, in 351 enhancers, STAT3 binding was markedly increased in the dual treatment compared to IL-6 treatment alone, suggesting a supporting role for IL-1β in assisting STAT3 loading at a subset of enhancers. This sub-population of enhancers had lower motif scores compared to unassisted STAT3 binding sites, indicating optimal STAT3 binding at these enhancers might require some facilitation by other factors. Accordingly, these enhancers were less active at the untreated state, but increased in activity following IL-1β treatment, an effect we termed 'IL-1β priming'. Our results are consistent with a scenario whereby IL-1β-activated TFs (C/EBPβ, AP1 and/or NFκB) assist STAT3 loading by binding a subset of enhancers, activating them thereby augmenting STAT3 binding. This unexplored mechanism of transcriptional regulation by cytokines may be targeted to alleviate the deleterious effects of pro-tumorigenic inflammatory programs. Citation Format: Ido Goldstein, Songjoon Baek, Myong-Hee Sung, Gordon L. Hager. Pro inflammatory cytokines induce synergistic gene expression by assisted loading of STAT3 at a subset of primed enhancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5510. doi:10.1158/1538-7445.AM2017-5510


Thymectomy is often an extremely useful therapeutic procedure in myasthenia gravis (MG) and is usually indicated for adult patients with generalized disease. Because remnants of thymus may remain in extrathymic fat, an extended thymectomy is recommended. A new surgical approach without sternotomy: video-assisted thoracoscopic extended thymectomy (VATET) was performed in 30 MG patients. The weight of removed thymus ranged from 10.8 to 113 grams. The weight of fatty tissue removed from pretracheal, anterior mediastinal and costophrenic areas ranged from 6.3 to 74.8 grams. Histological examination revealed thymic remnants in 14.8% of pretracheal fat samples and in 33.3% of samples from anterior mediastinal plus costophrenic areas. These findings indicate that VATET is a radical procedure and may be the first choice surgery for young female MG patients, since aesthetic sequelae are reduced compared to procedures involving sternotomy.


This paper compares three estimation strategies: mixed regression, fixed-effect regression and random-effect regression, based on the provincial (municipal) panel data of China from 2006 to 2015. By examining the individual and structural effects of the data, it finds that the fixed effect model is suitable for this study. Using the variables of urban residents' basic endowment insurance fund expenditure, endowment insurance coverage rate and endowment insurance contribution rate, it establishes a fixed effect variable coefficient model to analyze the relationship between urban residents' basic endowment insurance system and urban residents' per capita consumption expenditure. The results show that increasing the expenditure of basic endowment insurance fund and improving the coverage rate of basic endowment insurance can improve the consumption level of urban residents. The marginal propensity to consume disposable income of urban residents in the current period is larger than that of the basic endowment insurance fund, which indicates that disposable income in the current period can affect the current consumption of urban residents more.


A novel computational method based on a genetic algorithm was developed to study composite structure of promoters of coexpressed genes. Our method enabled an identification of combinations of multiple transcription factor binding sites regulating the concerted expression of genes. In this article, we study genes whose expression is regulated by a ligand-activated transcription factor, aryl hydrocarbon receptor (AhR), that mediates responses to a variety of toxins. AhR-mediated change in expression of AhR target genes was measured by oligonucleotide microarrays and by reverse transcription-polymerase chain reaction in human and rat hepatocytes. Promoters and long-distance regulatory regions (>10 kb) of AhR-responsive genes were analyzed by the genetic algorithm and a variety of other computational methods. Rules were established on the local oligonucleotide context in the flanks of the AhR binding sites, on the occurrence of clusters of AhR recognition elements, and on the presence in the promoters of specific combinations of multiple binding sites for the transcription factors cooperating in the AhR regulatory network. Our rules were applied to search for yet unknown Ah-receptor target genes. Experimental evidence is presented to demonstrate high fidelity of this novel in silico approach.


Recent research suggests that major meteorite impact events into a Late Hesperian/Early Amazonian ocean likely produced a mega‐tsunami that would have resurfaced coastal areas in northwestern Arabia Terra. The orientations of the associated lobate deposits, a conspicuous type of landforms called Thumbprint Terrain, suggests that if an impact event triggered the mega‐tsunami, the most likely location of the source crater is within the northern plains regions situated north of Arabia Terra. This study focuses on the identification of impact craters that impacted into the ocean and are likely to have produced the tsunami. We selected 10 complex impact craters, based on their diameters, location, and geomorphic characteristics. Of those, the Late Hesperian ~120‐km‐diameter Lomonosov crater exhibits a unique topographic plan view asymmetry (compared to other similar‐sized and similar‐aged craters in the northern plains such as Micoud, Korolev, and Milankovic). We attribute its broad and shallow rim, in part, to an impact into a shallow ocean as well as its subsequent erosion from the collapsing transient water cavity. The likely marine formation of the Lomonosov crater, and the apparent agreement in its age with that of the Thumbprint Terrain unit (~3 Ga), strongly suggests that it was the source crater of the tsunami. These results have implications for the stability of a late northern ocean on Mars.


In a study on self-presentation in everyday social encounters, 100 undergraduate students described their social interactions for two weeks using a variant of the Rochester Interaction Record. For each interaction, participants described their self-presentational goals and perceived success in achieving these goals. A series of multilevel random coefficient modeling analyses found that wanting to be liked was a particularly important goal. Moreover, goals and perceived success depended strongly on the type of situation people were in. For example, people wanted to appear competent during work-related interactions but interesting and attractive during romantic interactions. Overall, participants were relatively satisfied with their self-presentations. Self-presentational goals were more important in interactions with close others (family and friends) than with strangers or acquaintances. Furthermore, interactions with close others were considered especially successful. Participants felt least successful about their self-presentational performance during work related interactions and most successful about their performance during romantic interactions. Overall, social goals were more important than performance goals, and more of the variance in aspirations and perceived success was within-person (i.e., across interactions) than between-persons.


Background: To mitigate the spread of the COVID-19 coronavirus, some countries have adopted more stringent non-pharmaceutical interventions in contrast to those widely used (for e.g. the state of Kuwait). In addition to standard practices such as enforcing curfews, social distancing, and closure of non-essential service industries, other non-conventional policies such as the total confinement of highly populated areas has also been implemented. Methods: In this paper, we model the movement of a host population using a mechanistic approach based on random walks, which are either diffusive or super-diffusive. Infections are realised through a contact process, whereby a susceptible host may be infected if in close spatial proximity of the infectious host. Our focus is only on the short-time scale prior to the infectious period, so that no further transmission is assumed. Results: We find that the level of infection depends heavily on the population dynamics, and increases in the case of slow population diffusion, but remains stable for a high or super-diffusive population. Also, we find that the confinement of homogeneous or overcrowded sub-populations has minimal impact in the short term. Conclusions: Our results indicate that on a short time scale, confinement restrictions or complete lock down of whole residential areas may not be effective. Finally, we discuss the possible implications of our findings for total confinement in the context of the current situation in Kuwait.


Investigation of Alternatives for Migrating the One-Stop-Shop (OSS) Application to a Single, Web-Based Offering that is Conducive for both Desktop and Mobile Use. by Sahiti Katragadda, Master of Computer Science Utah State University, 2018 Major Professor: Dr. Douglas Galarus Department: Computer Science The One-Stop-Shop (OSS) application provides real-time data which is helpful for travelers in the Western United States in planning their travel. Included is traditional information (routing, imagery, weather), as well as points of interest and other routespecific information (elevations, rest areas, etc.). The system displays real-time data streams in a web-based application and in a separate mobile web application, which are presented to end users in a user-friendly format. OSS web application and OSS mobile web application features have been examined and the best design features for the mobile application have been identified. Along with that, additional design features are recommended to make the mobile app user-friendly and intuitive. The first question that needs to be addressed before starting the redesign is, "Do we need a separate mobile web application, or can we directly convert a website into a mobile application?" This is addressed in the report. Google analytics reports were also used to identify predominant features in website and mobile app that can be emphasized in the prototype. A prototype for the application has also been developed considering the essential features of the web application that can be incorporated into the mobile application. The mobile web application cannot currently be deployed in an app store as it is not an Android or iOS app. Wrapping the mobile web application into native iOS and Android apps were examined. Different methods were evaluated to convert the application into a cross-platform, mobile application, including the usage of Apache Cordova and online app builders. Results were documented to develop an effective, user-friendly mobile web application that can be deployed in app stores. OSS – All Roads. All Routes. One Stop. (58 pages)


BACKGROUND
Levels of measles in England and Wales are at their highest for 18 years, and strategies targeting the different groups of parents who do not vaccinate their children continue to be needed. Decision aids for decisions regarding childhood immunisation appear to be effective in achieving an increase in vaccine uptake but their cost effectiveness is unknown.

AIM
To assess the cost effectiveness of a web-based decision aid to increase uptake of the MMR vaccine.

DESIGN AND SETTING
Economic evaluation conducted alongside a cluster randomised controlled trial using urban GP practices in the north of England.

METHOD
Fifty GP practices in the north of England were randomised to one of three trial arms: decision aid, leaflet, usual practice. A total of 220 first-time parents (child aged 3-12 months) were recruited. Parents self-reported their contacts with the NHS and other previous/expected resource utilisation; associated costs were calculated. Vaccine-uptake data were collected from GP practices. A cost-effectiveness analysis was undertaken and provided the incremental cost per first-vaccine uptake. Multiple imputation was used to account for missing data and findings were adjusted for baseline differences in parents' levels of decisional conflict regarding MMR vaccination.

RESULTS
Of the 220 first-time parents recruited to the study, 179 completed the baseline and post-intervention questionnaires. MMR uptake was highest for those receiving the decision aid (42 out of 42, 100%) versus usual practice (61 out of 62, 98%) and leaflet arm (69 out of 75, 92%), and was associated with lower cost (-£9.20 versus usual practice and -£7.17 versus leaflet).

CONCLUSION
The decision aid has a high chance of being cost effective, regardless of the value placed on obtaining additional vaccinations. It also appears to offer an efficient means of decision support for parents.


: Buprenorphine has pharmacologic advantages over methadone, especially buprenorphine ' s better safety pro fi le. The true signi fi cance of buprenorphine ' s introduction lies in returning the care of those suffering from opioid use disorder (OUD) to the hands of the physician. The clinical success of buprenorphine has been meager, in part because most physicians have not been exposed to treating these patients. For physicians inclined to treat OUD, the barriers to buprenorphine ' s implementation have been onerous and largely counter to the norms of medical practice. Some notable concerns pertain to buprenorphine ' s clinical pharmacology like street diversion, unintended use and accidental poisoning. Recently, injectable buprenorphine preparations have been introduced to mitigate these latter short-comings. Yet, the injectable preparations ' clinical and commercial success has fallen far short of expectation. Here, we review the clinical pharmacology of these products and their expected clinical advantages for the manufacturers, clinicians, policy makers and patients, and offer our perspective, as clinicians and researchers, on how things can improve. Questions remain whether clinicians are willing to overcome barriers to treat OUD using these medications.


Nowadays it is impossible to think about Schulz outside Drogobych. Wherever else he showed up, be it Vienna, Marienbad, Kudowa, Zakopane, Warsaw or Paris, he was a refugee, a patient, a visitor or a tourist – always a stranger. And he considered himself one, while others did the same. To an extent, it was his own fault. It could perhaps be otherwise if he did not so often write in his letters (and most likely said in conversations) that he was unable to live and work outside his hometown. But the words of the writer could only encourage others to contribute to a stereotype of a "modest schoolteacher from a small town." The provincial status of Schulz, however, is not so obvious. At the end of the 19th century, thanks to oil Drogobych reached the end of centuries long stasis from which even the salt mines opened in the Middle Ages could not save it. Oil changed the life of many people in Galicia. Without leaving Drogobych, Schulz could actually watch and personally experience in doses which let him keep his independence and inner stability the rise of a metropolitan mentality described by Georg Simmel. Yet Paris was too much for him – after three weeks he escaped from the French capital with not a single word of commentary. To live in the capital of the 19th century, as Walter Benjamin called it, would have been a torture for him. Thus Schulz did not cancel the opposition of center and periphery, the capital and the provinces, but turned such distinctions upside down. Thanks to writing, the center of the world moved to his hometown so that perhaps Drogobych became the capital of the 20th century.


The approach to quality and standards in Scotland is enhancement-led and learner-centred. It was developed through a partnership of the Scottish Funding Council (SFC), Universities Scotland, the National Union of Students in Scotland (NUS Scotland) and the Quality Assurance Agency for Higher Education (QAA) Scotland. The Higher Education Academy has also joined that partnership. The Enhancement Themes are a key element of a five-part framework which has been designed to provide an integrated approach to quality assurance and enhancement, supporting learners and staff at all levels in enhancing higher education in Scotland drawing on developing, innovative practice within the UK and internationally.

 The five elements of the framework are:
 * a comprehensive programme of subject-level reviews undertaken by the higher education institutions themselves; guidance on internal reviews is published by SFC (www.sfc.ac.uk)
 * enhancement-led institutional review (ELIR) run by QAA Scotland (www.qaa.ac.uk/reviews/ELIR)
 * improved forms of public information about quality; guidance on the information to be published by higher education institutions is provided by SFC (www.sfc.ac.uk)
 * a greater voice for students in institutional quality systems, supported by a national development service - student participation in quality scotland (sparqs) (www.sparqs.org.uk)
 * a national programme of Enhancement Themes aimed at developing and sharing good practice to enhance the student learning experience, which are facilitated by QAA Scotland (www.enhancementthemes.ac.uk).

 The topics for the Themes are identified through consultation with the sector and implemented by steering committees whose members are drawn from the sector and the student body. The steering committees have the task of developing a programme of development activities, which draw upon national and international good practice. Publications emerging from each Theme are intended to provide important reference points for higher education institutions in the ongoing strategic enhancement of their teaching and learning provision.
Full details of each Theme, its steering committee, the range of research and development activities, and the outcomes are published on the Enhancement Themes website (www.enhancementthemes.ac.uk). To further support the implementation and embedding of a quality enhancement culture within the sector, including taking forward the outcomes of the various Enhancement Themes, a new overarching committee has been established, chaired by Professor Kenneth Miller (Vice-Principal, University of Strathclyde). It has the important dual role of supporting the overall approach of the enhancement themes, including the five-year rolling plan, and of supporting institutional enhancement strategies and management of quality. We very much hope that the new committee, working with the individual topic-based Themes' steering committees, will provide a powerful vehicle for the progression of the enhancement-led approach to quality and standards in Scottish higher education.


In this work, the stiffness of a glass/epoxy composite material system subject to three-point bend fatigue is tracked throughout life. Linear curve fits of the data are used to develop phenomenological models of the response. Predictions of when failure will occur are made using the models and data for a particular specimen up to a prescribed number of cycles. Final fracture was predicted within 12%. The model based on the slope of the modulus vs. cycles curve was found to be less conservative than the model based on the intercept of the modulus vs. cycles curve. At 50% of life, the number of cycles to final fracture was predicted with an average error of 32%.


Communication over wireless links identifies significant challenges for routing protocols operating. This paper proposes a Cross-layer design based Multipath Routing Protocol (CMRP) for mobile ad hoc networks, by means of the node energy signal from the physical layer. The purpose is to optimize routing decision and path quality. The nodes' mobility behavior is predicted using a notion of "Signal Fading Degree, SFD". Especially, in combination of the IEEE 802.11e standard at the MAC layer, we determine that the IEEE 802.11e makes a significant contribution to performance improvement of CMRP. Performance evaluation of AODV in legacy 802.11 and CMRP in IEEE 802.11e shows that, as a function of speed of node mobility, a tremendous reduction achieved, in metrics such as the average end-to-end delay, route overhead, route discovery frequency, normalized routing load - almost more than 80%, 40%, 40%, and 40%. In the case of varying number of sessions, the reduction for route discovery frequency and normalized routing load are up to 70% and 80%.


In this paper, we analyze the error caused by the beamspace transform (BT) when it is applied to uniform circular array (UCA) configuration. Several algorithms for direction of arrival (DoA) estimation exploit this modal transform because it allows using computationally efficient techniques such as polynomial rooting and dealing with coherent sources. The BT is based on the phase-mode excitation principle. The performance of such DoA estimators is degraded if the array has a small number of elements. We introduce a modified beamspace transform (MBT) that performs mapping from element-space to beamspace domain taking into account the error caused by the transform. Justification of the difference in the statistical performances of MUSIC and root-MUSIC algorithms for UCA is also given. Moreover, we show that there is a significant difference in the performance of the UCA root-MUSIC technique depending on whether an even or odd number of elements is used. We derive an expression approximating the bias in the DoA estimates that is caused by the beamspace transform. Some design guidelines are provided for choosing the key UCA configuration parameters such as number of sensors, array radius, and interelement spacing in order to reduce the error. Finally, we propose a novel technique for bias removal. It allows practically bias-free DoA estimation


Social Capital is an emergent field of study that has the potential of applications in a wide variety of fields, from public health to economics, but most widely for human well-being. This study is a spatial and statistical analysis of the relation between commonly accepted indicators of wellbeing, commonly accepted indicators of social capital, and socio-economic factors within Toronto, as well as their respective spatial patterns. This research discovered that within Toronto there does not exist a clear link between wellbeing and social capital indicators, both in terms of statistical regression analysis and spatial pattern comparison. The results suggest that, at least within the context of Toronto, much of the research surrounding the effects of high social capital on wellbeing are not applicable, at least using the methods demonstrated in this study.


OBJECTIVE
This study examines parents' and children's exposure to short-term political violence and the relation between childrearing violence and child adjustment following widespread violence that erupted in Kisumu, Kenya after the disputed presidential election in December 2007.

METHOD
Mothers of 100 Luo children (mean age = 8.46 years, 61% female) reported on their own use of childrearing violence at Time 1, approximately 4 months after the disputed election, and again at Times 2 (n = 95) and 3 (n = 95), approximately 12 and 24 months later, respectively. At Time 2, mothers reported about post-election violence directed at them and about their children's exposure to post-election violence. Children reported about their own externalizing behaviors at Times 1, 2, and 3.

RESULTS
Children's exposure to post-election violence was related to Time 2 externalizing behavior, and childrearing violence at Time 1 predicted child externalizing behavior at Time 2. Exposure to post-election violence was not directly related to either childrearing violence or children's externalizing behavior by Time 3, although children's externalizing at Time 2 predicted more childrearing violence at Time 3.

CONCLUSION
These results support earlier work that links childrearing violence and children's exposure to political violence with increases in child externalizing behavior, but examined these links in the under-studied area of short-term political violence. Even though sudden and severe political violence may subside significantly in weeks or months, increased attention to long-term effects on parenting and child adjustment is warranted.


Since the turn of the 21 century there has been a prolific interest in the wellbeing of children and young people globally, nationally and regionally. The interested parties have ranged from politicians, academics, educators and third sector organisations. The sometimes emotionally charged concern of the interested parties has resulted in education being given a greater responsibility for improving the wellbeing of children and young people. A plethora of interventions have been created and implemented to solve the 'problem' of childhood fragility, whilst the United Kingdom has experienced severe cuts to children's services. This study explored what wellbeing means to young people in one secondary school and how this relates to policy discourses on wellbeing. The literature review provided insights into the research practices carried out in the area of wellbeing and schools and showed the different levels of participation in the chosen methods. Child centred practices emerged from the United Nations Convention on the Rights of the Child (1992) and participatory approaches with young people in schools have been embedded to various levels of authenticity in the research studies included in the review. The study illustrates the complexity of the wellbeing agenda and the need for policy making and research practices to be more authentically participatory in nature. Following analysis of the discourses on wellbeing evident in key education policies such as Getting it Right for Every Child and Curriculum for Excellence, the case study design used a thematic analysis to explore how sixteen young people in one secondary school in Scotland understand the term 'wellbeing'. Young people firstly completed a creative task and then participated in four focus groups to explore their interpretation of the term 'wellbeing', specifically the eight wellbeing indicators of 'Safe; Healthy; Achieving; Nurtured; Active; Respected; Responsible; Included'. The participants were selected from the S1 and S2 cohort in one rural secondary school in the north of Scotland (mean age 12 years and one month in S1 and 13 years in S2). Eight females and eight males participated in the single sex focus groups. The study aimed to gain an insight into the participants' understanding of wellbeing and to explore how this compared to the definitions used in the Scottish policy context. The policy analysis highlighted the complexity of the definitions used in the Scottish policy context and illustrated how the term 'wellbeing' is often ambiguous and interpreted in multifaceted ways, sometimes in one context. The study demonstrated that the young people participating in the focus groups and creative task were fully able to contribute to, and participate in, conversations with their peers which illustrated their understanding of the holistic term 'wellbeing'. The data analysis revealed that young people in this study referred to a multi-faceted definition of wellbeing with a strong focus on love and trust. Suggestions for the implications flowing from my research data include that the contrasting narratives located in the policy discourses need to be critiqued more deeply to ensure that schools and other educational establishments are making the right choices for those they aim to serve. This could be explored more deeply in specific contexts through working in a participatory manner with those the wellbeing agenda impacts on, facilitating opportunities to capture minority voices.