Flavivirus replication is mediated by a complex machinery that consists of viral enzymes, nonenzymatic viral proteins, and host factors. Many of the nonenzymatic viral proteins, such as NS4B, are associated with the endoplasmic reticulum membrane. How these membrane proteins function in viral replication is poorly understood. Here we report a robust method to express and purify dengue virus (DENV) and West Nile virus NS4B proteins. The NS4B proteins were expressed in Escherichia coli, reconstituted in dodecyl maltoside (DDM) detergent micelles, and purified to >95% homogeneity. The recombinant NS4B proteins dimerized in vitro, as evidenced by gel filtration, chemical cross-linking, and multiangle light scattering experiments. The dimeric form of NS4B was also detected when the protein was expressed alone in cells as well as in cells infected with DENV type 2 (DENV-2). Mutagenesis analysis showed that the cytosolic loop (amino acids 129 to 165) and the C-terminal region (amino acids 166 to 248) are responsible for NS4B dimerization. trans-Complementation experiments showed that (i) two genome-length RNAs containing distinct NS4B lethal mutations could not trans-complement each other, (ii) the replication defect of NS4B mutant RNA could be restored in cells containing DENV-2 replicons, and (iii) expression of wild-type NS4B protein alone was not sufficient to restore the replication of the NS4B mutant RNA. Collectively, the results indicate that trans-complementation of a lethal NS4B mutant RNA requires wild-type NS4B presented from a replication complex.


The internal noise spectrum in miniature electret microphones of the type used in the manufacture of hearing aids is measured. An analogous circuit model of the microphone is empirically fit to the measured data and used to determine the important sources of noise within the microphone. The dominant noise source is found to depend on the frequency. Below 40 Hz and above 9 kHz, the dominant source is electrical noise from the amplifier circuit needed to buffer the electrical signal from the microphone diaphragm. Between approximately 40 Hz and 1 kHz, the dominant source is thermal noise originating in the acoustic flow resistance of the small hole pierced in the diaphragm to equalize barometric pressure. Between approximately 1 kHz and 9 kHz, the noise originates in the acoustic flow resistances of sound entering the microphone and propagating to the diaphragm. To further reduce the microphone internal noise in the audio band requires attacking these sources. A prototype microphone having reduced acoustical noise is measured and discussed.


The barbarian of interpretation, in his barbarity, cannot be omitted from the line of 'the new barbarians'. In the following, I will underline not only the threatening side of the barbarian of interpretation, but also the fact that the entirety of modern hermeneutics appeared in order to offer a certain protection from 'the invasion' of these strange barbarians disguised as gentle scholars, commentators and interpreters. As an irony of fate, hermeneutics, the science that was supposed to protect civilization from the barbarity of interpretation, has become a terrible weapon used by these barbarians to intensify their attacks, as has always happened in history with the weapons captured by the barbarian hoards from the protectors of civilization.


The continuous waves in digital innovations over the past few years, and the sweeping changes anticipated by disruptive mobility, have inspired visions of a very different future as well as a good deal of hype. To distinguish between the hype and reality, this chapter discusses the role of disruptive technologies within low carbon mobility networks and describes how digital innovations are changing the urban mobility landscape, enabling real-time measurement and analysis of urban mobility, and promoting sustainable smart cities. The chapter maps the value of data-driven innovations in mobility and draws on practical applications, case studies and modelling results to demonstrate the benefits. The chapter also describes the major behavioural and technological changes, and the new mobility business models that would be required to achieve the desired targets and outcomes. Finally, the chapter provides a reflection of the value derived from typical smart mobility `use cases'. It then identifies the policy principles which are central to the success of smart mobility, and how it will give our cities an opportunity to modernise transport systems and help drive economic growth and create jobs for the twenty-first century.


IN THE FALL OF 2002 I received a call from Karen Kenton, an executive producer at WETA, the Washington, D.C., public television station. She asked me whether I would be interested in producing a film about the history of deafness in the United States. I live only a few minutes away from the Clarke School for the Deaf in Northampton, Massachusetts, and less than an hour's drive from the American School for the Deaf in Hartford, Connecticut, so I had heard more than a little about the issues of deaf education. I knew that the story was bound to contain drama, tension, characters, and emotion. In fact, I was well aware that if we were not careful we could be stepping into a hornet's nest. Of course, this sounded like good television, so I asked Karen to tell me more. She said that, in the summer of 2002, Dr. I. Kingjordan, president of Gallaudet University, had contacted Sharon Rockefeller, president and CEO of WETA, to discuss the possibility of collaborating on a documentary film inspired by the exhibition History through Deaf Eyes, which was on display at the Smithsonian Institution in Washington, D.C. Recognizing Gallaudet's access to a vast collection of archival materials and other resources, WETA readily agreed to take on the project. Believe me, this kind of thing doesn't usually happen. It can take years to convince a major PBS station to get interested, but WETA knew right away that this was no ordinary subject and that this should be no ordinary film. Then they called me. I had worked with WETA a few years before, producing a film called Divided Highways: The Interstates and the Transformation of American Life. The subject, not unlike the history of deafness in the United States, was vast, and I knew that there were more car and highway motion picture archives than any other kind in the country. But as we started scouting the locations for the film, I got more and more worried. The interstates, perforce, had been built to federal standards, and they all looked exactly alike. Another problem was that you can't just take interview subjects and plunk them down next to the highway and start asking questions. Besides the bugs and the noise and the police you could get yourself killed. So I came up with the idea to shoot everyone in the film against a green screen, the same kind that special-effects people use to make actors fly and meteorologists use to project maps. In that way I could place people wherever I wanted, keep the feeling of movement, which is important in a highway film, and do it all from the comfort of a hotel room. To give you a little sense of our style and the techniques we use to try to keep viewers' hands off their remote control buttons, here are the first few minutes of Divided Highways, [clip shown] This film did very well. It won an Emmy and a Peabody and is in use in schools across the country. It's a good example of how to take a history of a subject that parallels the history of our country and make it lively and relevant for a broad spectrum of the population. That is a challenge we face with History through Deaf Eyes as well. So, how do we approach a film about the history of deafness? History through Deaf Eyes will have a dual focus. Part of its subject is deafness from the inside: the personal experiences of deaf people (and hearing people with deaf children or parents). The film will take its viewers into the homes and lives of deaf people to show what is different-and what is just the same-in the Deaf world. However, the center of the film will be the larger picture: the history of Deaf culture as a whole-how a community came into being and what that circle has meant to its members for nearly two centuries. It is a history that has all of the elements of a classic American saga. It's a story with a perfect dramatic arc, complete with plot points-the long rise from near nonexistence, the sudden fall and resulting crisis, then the final triumph . …


This research tried to find the type of compliments and the compliment responses used by the main characters in the movie "What Women Want". The research tried to find the type of compliments produced by the main female character (Darcy). Furthermore, the research also tried to find the types of compliment responses produced by the main male character (Nick). The main theory of compliments and compliment responses was Herbert?s theory (1989). This research was a descriptive qualitative research. The writer got the data from the utterances in the conversations between the two main characters in the movie that the writer grabbed from the script. In her analysis, the writer classified the compliments into three, that is, compliments on appearance, compliments on skills/ abilities and compliments on possessions. However, the writer found a type of compliment that did not belong to Herbert?s theory. The type is compliment on personality. Moreover, the writer also classified the compliment responses. Finally, the writer concluded that social status and gender did not always influence the way Darcy as a female superior character gave compliments toward Nick as a male subordinate character. Moreover, social status and gender did not influence the way Nick responded Darcy?s compliment. Besides, the writer found that personal feeling was the one that influences the way Darcy complimented when the relationship between them (Nick and Darcy) was getting closer and closer.


In this dissertation I present three essays. The overarching theme of these projects is how price-discriminating sellers endogenously modify their pricing schemes in the face of regulatory interventions. The application I have in mind when writing the papers is that of a food retailer deciding menu characteristics, such as price and quantity, in the context of a given food policy environment. The particular policies I consider are portion cap rules and taxes, both designed by the policy-maker to reduce the consumption of certain foods and ingredients. My approach diverges from studies focusing on buyers' reactions to paternalistic food policies by placing the seller at the center of the analysis. I use models of nonlinear pricing to derive hypotheses, which I test in controlled laboratory experiments. In the first two essays I explore the economic impacts of taxes and portion cap rules when single-product sellers serve privately informed buyers. In the third, I examine the economic effects of portion cap rules when two-product sellers serve buyers with private preferences. In the first essay, collective work with Dr. Joseph Balagtas and Dr. Steven Wu, I compare the impacts of taxes and portion control rules on profit and consumer surplus. I model the pricing problem of a single-product seller serving two types of privately-informed customers. I aim to answer the following questions: i) what effects do taxes have on portion sizes, buyer surplus, and seller's expected profit; ii) how does the tax affect the seller's ability to screen the market, and iii) how the effects of taxes and portion cap rules compare. I find that under a tax regime, all package sizes are smaller; high willingness to pay buyers see a reduction in their surplus, and the retailer's expected profit is unambiguously diminished. Both policy instruments curb consumption. In contrast with tax regimes, however, cap rules leave buyer surplus unaffected. These outcomes suggest that portion control rules might be a preferred over tax regimes as methods to regulate consumption of calorie-dense and low-nutrient foods traded in settings where retailers engage in second-degree price discrimination.In the second paper, also joint work with Dr. Joseph Balagtas and Dr. Steven Wu, I report a controlled laboratory experiment designed to test the results of my first essay. In this project, human subjects take on the role of sellers and are free to decide their pricing strategies, including number of ``packages'', their price and their quantity. We vary the policy environment across treatments,and these include: unregulated baseline, cap rule, and specific tax. My principal goal is to test the theoretical outcomes of the first essay and find which regulation is associated with a smaller negative impact on consumers' economic surplus in the laboratory. My main finding is that the cap does not impact buyers' information rents regardless of the seller's segmentation scheme; while the effect of the tax is contingent on the seller's strategy and is neutral at best.In the last essay, I study the economic impacts resulting from enforcing a maximum-quantity limit on one of the two products offered by a seller facing demand from privately-informed heterogeneous buyers. Specifically, I look at impacts on: i) consumption of the regulated component, ii) purchases of the unregulated item, and iii) consumer surplus. Hypotheses derived from a bi-dimensional nonlinear pricing predict reductions in consumption of the target component, changes in consumption of the unregulated product by some buyers, and mixed impacts on consumer surplus. Data from a laboratory experiment corroborates the predictions regarding consumption of the regulated good; however, no significant changes in consumption of the unregulated product are found, surprisingly a subset of buyers are better-off after the cap rule while no buyer type is worse-off. The results have implications for food policy discussions around portion cap rules, where the assumption that these regulations negatively impact consumers' well-being largely drives public debate.


Globalisation of the economy has lead to an increased competition in what is rapidly becoming a universal market. While the manufacturing sector has been relatively quick in responding to the changing business environment, the construction industry has lagged behind. The manufacturing industry has derived great benefits from measuring its performance through critical success factors as a part of a regime of continuous improvement. The construction industry can adopt similar practices of performance measurement and comparison to develop a culture of 'lean construction' through continuous improvement. The objective of this approach is to lower costs and increase productivity, resulting in a sustained competitive edge. This approach will involve development of metrics for performance measurement and benchmarking them with the best. This paper looks at the elements of lean production and lean construction, as well as the current practices, issues and outcomes of performance measurement and benchmarking. Some of the key performance issues that could be targeted for improved productivity in the construction industry are highlighted along with the potential benefits that would accrue to the industry.


Beedi manufacturing is the second largest industry in India. It provides employment to millions of women mostly from the poor socioeconomic class. In Telangana, beedi rolling is a major occupation for illiterate women in many villages. They are exposed to unfiltered tobacco dust and volatile compounds containing hazardous chemicals while making beedis as they do not use any protective wear. The purpose of this study was to assess the reproductive outcome and health problems and haematological parameters among rural women beedi rollers of Jagitial district. A total of 230 women beedi rollers of reproductive age and 200 women in the same age group (controls) and not occupationally exposed to any chemical or physical agents were enrolled and a questionnaire based survey was conducted. A high frequency prevalence of abortions, premature births, neonatal births, still births and a significantly decreased fertility rate were observed among the beedi rollers. The study also indicated a high frequency of the health problems and haematological studies shown the decreased mean values in all the parameters except Lymphocytes in rural women beedi rollers when compared with the control group.


Research into developing effective computer aided techniques for planning software projects is important and challenging for software engineering. Different from projects in other fields, software projects are people-intensive activities and their related resources are mainly human resources. Thus, an adequate model for software project planning has to deal with not only the problem of project task scheduling but also the problem of human resource allocation. But as both of these two problems are difficult, existing models either suffer from a very large search space or have to restrict the flexibility of human resource allocation to simplify the model. To develop a flexible and effective model for software project planning, this paper develops a novel approach with an event-based scheduler (EBS) and an ant colony optimization (ACO) algorithm. The proposed approach represents a plan by a task list and a planned employee allocation matrix. In this way, both the issues of task scheduling and employee allocation can be taken into account. In the EBS, the beginning time of the project, the time when resources are released from finished tasks, and the time when employees join or leave the project are regarded as events. The basic idea of the EBS is to adjust the allocation of employees at events and keep the allocation unchanged at nonevents. With this strategy, the proposed method enables the modeling of resource conflict and task preemption and preserves the flexibility in human resource allocation. To solve the planning problem, an ACO algorithm is further designed. Experimental results on 83 instances demonstrate that the proposed method is very promising.


summary
The influence of a vesicular-arbuscular (VA) mycorrhizal fungus, phosphorus (P) fertilization, and soil microorganisms on growth and root architecture of big bluestem (Andropogon gerardii Vitroari) was investigated. In pasteurized soil, mycorrhizal inoculation significantly improved plant growth and increased root length and the number and the diameter of the primary, secondary and tertiary roots. These differences between mycorrhizal and non-mycorrhizal plants diminished with added P. In pasteurized soil amended with non-sterile soil sievate, differences between mycorrhizal and non-mycorrhizal plants were still obvious, but in many treatments these plants grew more poorly (had less dry weight, root length, number or diameter) than their counterparts in unamended pasteurized soil. Growth in non-sterile soil was also suppressed, and mycorrhizal responses were not detected since all of the plants in non-sterile soil became mycorrhizal whether or not they were inoculated. Two analyses of calculated parameters which describe root-system architecture were conducted. The first, specific root length (SRL), revealed that mycorrhizal symbiosis dramatically alters root morphology in soils of low fertility. These changes were similar to the changes evoked by added P. The second, path length (Pe) revealed that mycorrhizal fungi (and to some degree other soil microbes) significantly alter root architecture by reducing the relative amount of root branching. Apparently, mycorrhizal plants develop a more elongate, exploratory growth pattern which permits the fungal hyphae to extract nutrients from a larger volume of soil. In contrast roots of non-mycorrhizal plants maintain a more highly branched pattern of root growth, and the roots themselves play a more critical role in the direct extraction of nutrients from the soil. These differences in root topology were not directly associated with the concentration of exogenous P, but instead appeared to be controlled by the mycorrhizal fungi themselves. Thus, while internal P content of plants mediates the establishment of the mycorrhizal symbiosis, the fungi can alter the root architecture of the plant to a form which best accommodates the symbiosis under the prevailing fertility and rhizosphere conditions in the soil. By altering root-system architecture in this manner, the mycorrhizal fungi can control, at least to some degree, the dependence of the host on the symbiosis. Thus, the topology of the root system is contingent upon the microflora in the rhizosphere. The topological analysis revealed differences in root architecture not detected by any of the other measures of root morphology. These differences suggest that mycorrhizal fungi affect root architecture and plant growth in ways not directly associated with phosphorus uptake.


We present a new framework for sketch-based modeling and animation of 3D organic shapes that can work entirely in an intuitive 2D domain, enabling a playful, casual experience. Unlike previous sketch-based tools, our approach does not require a tedious part-based multi-view workflow with the explicit specification of an animation rig. Instead, we combine 3D inflation with a novel rigidity-preserving, layered deformation model, ARAP-L, to produce a smooth 3D mesh that is immediately ready for animation. Moreover, the resulting model can be animated from a single viewpoint --- and without the need to handle unwanted inter-penetrations, as required by previous approaches. We demonstrate the benefit of our approach on a variety of examples produced by inexperienced users as well as professional animators. For less experienced users, our single-view approach offers a simpler modeling and animating experience than working in a 3D environment, while for professionals, it offers a quick and casual workspace for ideation.


The Triangulation Problem consists in finding a simultaneous permutation of rows and columns of a given square matrix, so that the sum of the upper-diagonal entries is maximal. The researchers study this problem intensively, as it has major applications in broad domains. A new hybrid Ant Colony Optimization algorithm is introduced. The algorithm starts with a greedy search procedure. It is followed by an improved version of the Ant Colony System mixed with a problem-specific local search.


The Black Book (in Russian, Chernaia kniga) was an encyclopedic anthology compiled between 1943 and 1946 about Nazi crimes against Jews in occupied Soviet territory. This paper argues that the people who worked together to produce the book—editors and writers mainly based in Moscow, and survivors throughout Soviet territories—inadvertently created a community through the attempt to document the catastrophe. The creation of The Black Book allowed its compilers to express a sense of communal and familial responsibility, grieve for their losses, and demonstrate as Jews their loyalty to the Soviet state that had defeated the Nazis.


reproductive organs which enable an understanding of the more in-depth explorations of changes that occur during the menopause. The pros and cons of Hormone Replacement Therapy are discussed at length. Sound advice is given in the chapters on diet and life styles. The development of the dreaded osteoporosis is clearly explained, advice on how to avoid bone loss or further deterioration is given. As well as covering physical problems, there comes over a sensitive understanding of the psychological problems of the menopause not only for women but also for their partners. This book has much to commend it as a health


This paper presents a new low cost GNSS Software (SW) receiver for Microsatellites. Syrlinks (Bruz, FRANCE) has been chosen by CNES for developing and manufacturing this equipment which should be tested on board the scientific microsatellite named MICROSCOPE that will be launched in 2015. The GNSS receiver under development is a highperformance equipment specially designed and optimized for the needs and constraints of small platforms for which small volume, low mass and low power consumption are important parameters. This equipment is based on COTS (Commercials Off The Shelf) in order to exploit the performance of the advanced technology developed for terrestrial applications and to reduce significantly the global cost of the equipment. The structure of this GNSS receiver is organized around a reconfigurable architecture with the use of one FPGA (Field Programmable Gate Array) associated with one DSP (Digital Signal Processor). The GNSS function is then split in two main parts according to the real time requirements of the processing and navigation operations. The hardware (HW) architecture has been optimized to be able to support a low power mode through a fractioned activity that has been implemented by introducing standby time frames during the mission. An orbital extrapolator is also implemented for propagating position and velocity without pseudo range measurements. This receiver is able to process GPS (L1) and GALILEO (E1) signals simultaneously in the first version of the software and will be able to evolve in a second step to a dual frequency mode, compatible with E5a/E1, or with E5b/E1. This GNSS receiver dedicated to low earth orbit (LEO) satellites will withstand the radiation environment therefore the hardware and software architecture has been defined to reduce the single event effects (SEE) and to maximize the service availability.


Opened in 1946, the Linda Hall Library in Kansas City, Missouri, is world renowned for its collections in science, engineering, and technology. Just as well known is the strong user orientation of its dedicated staff. While the library certainly collects all types of materials, including books, patent specifications, engineering standards, maps, and more, a particularly strong emphasis is placed on the collection of current journals. The library, a privately funded public library, is situated on fourteen acres surrounded by the University of Missouri-Kansas City, although there is no affiliation with that institution. Serials Review made a visit on a lovely spring day in June, as the day lilies and other flowers were in full riot.


Multi-center neuroimaging studies have more power than smaller ones to conduct sophisticated studies of basic neuroanatomy and clinical disorders. One important confound of combining images obtained from different scanners is the potential for scanner effects to introduce systematic error, thus making the interpretation of results difficult. Differences in diffusion imaging measurements due to scanner-dependent inaccuracies may either mimic or obscure true changes. In the context of multicentric Swiss project on brain connectivity in patients with epilepsy, we used DSI (Diffusion Spectrum Imaging) acquired on different scanners to address the limitation of DTI (Diffusion Tensor Imaging) where imaging of multiple fiber orientation in a single voxel is not possible. Since DSI is a very recent development of MRI there is no information on inter- and intra-site reproducibility, while concerning the DTI there are very few studies on a 3T scanner and even less on cross center reliability measures.


In the year 2006, only 10 years after the steel- concrete composite bridge, Varby bridge was built, fatigue cracks were found during an inspection. To further investigate the reasons and the potential danger of the cracks, an investigation under the commission of the Swedish Transport Administration was issued in 2009. After the detection of fatigue cracks, several measurements were carried out in order to monitor the static behavior by the use of strain gauges at selected positions along the bridge. The measurements from the strain gauges monitoring the global behavior were then used to calibrate an finite element model. The present report is part of the research of understanding the behavior of steel-concrete composite bridges. Numerical analysis and model updating have been used in order to understand and determine how different parameters affects the strain range and the global behavior. The numerical analysis and parameter study were performed in the Finite Element software Abaqus and programming language Python. The outcome of the parameter study was then used to perform the model updating by the method of falsification in MATLAB. The results from the parameter study and the model updating showed that the measured strains could be reached with a wide range of parameter combinations. Even with unreasonable parameter values, the measured strains were obtained. To investigate the reason for this, a multiple linear regression analysis was performed which showed that the strain range is strongly correlated to the Young's modulus of steel and concrete and also to the connector elasticity, which resembles the studs in the real bridge. Two different finite element models, with two completely different input parameter values, obtain the same strain range for the global behavior. It is therefore not certain to assume that a model is accurate and valid based on the fact that the predicted strain range from the finite element model is close to the measured strain range since the global behavior of a steel- concrete composite bridge can be modeled by many different sets of parameters.


Purpose: Rhabdoid tumors are rare but aggressive pediatric malignancies characterized by biallelic loss of INI1/hSNF5. Reintroduction of INI1 causes cell arrest and senescence in rhabdoid cells. Our purpose was to identify INI1-downstream genes and to determine their functional and therapeutic significance for rhabdoid tumors. Experimental Design:INI1 downstream targets in rhabdoid cells were identified using a cDNA microarray analysis and the expression of selected INI1 targets was confirmed by quantitative reverse transcription-PCR, Western analysis, and/or immunohistochemical analysis of rhabdoid cells and primary rhabdoid tumors. To determine the functional significance of downstream targets, activated targets of INI1 were induced and repressed targets of INI1 were knocked down (by using RNA interference) in rhabdoid cells, in the absence of INI1. Consequence of altered expression of INI1 downstream targets for rhabdoid cell survival, cell cycle, and apoptosis was assessed. Results: Microarray studies indicated that INI1 activated IFN-stimulated genes at early time points and senescence markers at late time points and repressed mitotic genes such as Polo like kinase 1 (PLK1), selectively in rhabdoid cells. Treatment of rhabdoid cells with recombinant IFNs resulted in induction of IFN-stimulated genes, G1 arrest, and flat cell formation. PLK1 was overexpressed in primary human and mouse rhabdoid tumors. RNA interference–mediated knock down of PLK1 in rhabdoid cells resulted in mitotic arrest, aberrant nuclear division, decreased survival, and induction of apoptosis. Conclusions: Targeting downstream effectors of INI1 such as IFN pathway and mitotic genes leads to antiproliferative effects in rhabdoid cells. IFN treatment and down-modulation of PLK1 constitute potential novel therapeutic strategies for rhabdoid tumors.


In this work, titanium dioxide nanotubes were grown via anodization of sputtered titanium thin films using different anodization parameters in order to formulate a method of producing long anatase titanium dioxide nanotubes intended for solar cell applications. The morphological features of the nanotubes grown via anodization were explored using a Philips XL30 Field Emission Scanning Electron Microscope. Furthermore, the grown nanotubes were also subjected to X-ray diffraction and Raman spectroscopy in order to investigate the effect of the predominant crystal orientation of the parent titanium thin film on the crystal phase of the nanotubes. After optimizing the anodization parameters, nanotubes with anatase TiO2 crystal phase and tube length more than 2 microns was produced from parent titanium thin films with predominant Ti(010) crystal orientation and using ammonium fluoride in ethylene glycol as an electrolyte with a working voltage equal to 60V during 1-hour anodization runs. Keywords: Nanotechnology, titanium dioxide, nanotubes, anodization


An inadequate number of suitably qualified and experienced supervisors, an increase in the number of students, uncertainty regarding the suitability of supervision and academic rigour in dissertations and theses make it difficult to produce quality graduates within the prescribed time-frame as stipulated by the Department of Education. By implication, a strategy is needed to help both students and supervisors overcome these difficulties and produce quality research within the minimum time-frames. In this article, an intervention to assist students with writing their postgraduate research is presented and the need, planning, validation and implementation thereof are described. Reflection, inductive reasoning and observation initiated the need for this study and formed part of the needs assessment for the intervention. A template was designed as the intervention and was used as a guideline for students to use, presenting the basic format pertinent to writing dissertations\theses. To evaluate the intervention, a questionnaire was applied to ascertain students' opinions about the intervention and was validated using face-validity. Responses were deemed reliable using the internal consistency for determining reliability. The study concluded that an intervention such as the template is beneficial and is an improvement from the traditional style of supervision and text-book teaching.


Sin, Crimes and Vices The criminal in 19th Century Denmark This article deals with the criminological thinking in Denmark in the period between 1789 - when a highly influential legislation on larceny was passed - and 1866 when a grand Penal Reform was introduced. The article is predominantly based on published material in the form of religious, legal, philosophical, psychological and quasi-academic literature dealing with the nature of Man and the reason of crime. During the European Enlightenment, traditional Christian doctrines about Man as having no Free Will and being sinful in nature were challenged by modern ideas about Man as free, rational, and inherently good. Generally, three perspectives on the criminal emerged from the Enlightenment: 1) a liberal/ liberal-conservative perspective highlighting the criminal as a free and rational (and therefore) immoral individual; 2) a contextual perspective emphasising the criminal as shaped by the environment; and 3) a structural perspective, representing the criminal as a (natural) by-product of structural conditions. In Denmark the liberal-conservative view of Man and the criminal (primarily associated with the German philosopher Immanuel Kant) dominated from the 1790s and onwards, although more contextual ideas gradually became incorporated in this bourgeois understanding of crime. At the root of crime was 'lust' in all its manifestations e.g. gambling, drunkenness, and sexual desire. Fundamentally, the criminal was a person who acted on his immoral impulses emanating from either evil will or an undeveloped moral sense. This understanding of the criminal comprised the foundation of the Larceny Legislation of 1789. In the following decades, this conventional bourgeois understanding of Man was frequently challenged by more materialistic and deterministic perspectives. Particularly, Gall's Phrenology became popular, but never gained permanent influence on the dominant discourse on Man and the criminal. Likewise, in 1824, the Danish doctor F.G. Howitz challenged the dominant discourse by claiming that Man essentially was constituted by his biology and his milieu. Although his ideas did not catch on immediately, many of his ideas can be seen in later psychiatric-medical discourses. In spite of his and even others' fundamental critique of the Kantian principles underlying the liberal-conservative view of Man, the Penal Reform of 1866 was to a large extent founded on exactly these Kantian principles. Ultimately, the bourgeois understanding of Man and the criminal was challenged by the growing influence of the field of psychiatry and moral statistics. These newly constructed scientific disciplines rather successfully questioned the key assumptions underlying the previous understanding of man as malleable and possessing a free will. By using positivistic methods generated from the natural sciences, which by this time had been elevated in the scientific hierarchy, they managed what other deterministic systems before had not been able to. The above description of the development of criminological discourses may be seen in relation to the overall development of the 'scientification' of scholarly discourse in the field of humanities and the process of secularisation. Additionally, it seems reasonable to view the construction of the 'immoral criminal' in relation to the construction of a distinctly bourgeois cultural identity. Similarly, it can be argued that the construction of the bourgeois ideal and the criminal being immoral, but at the same time malleable is associated with a new ordering of the mechanisms of social control and discipline.


The use of environmental sensors in agriculture and precision agriculture applications is becoming more common, although implementation strategies and capital costs prohibit widespread adoption by many in the industry. Typical costs for agricultural monitoring systems can be in the tens of thousands of dollars per site. This paper presents low cost, wireless sensor nodes and a corresponding low power network. The nodes use biodegradable plastic to house the sensor, support electronics, RF transceiver and a 433 MHz antenna. In this paper the antenna design and network topology is discussed together with the propagation problems associated with a field environment in which the vegetation changes weekly. It is envisaged that such a platform could be ploughed in to the field at the end of its working life. The total cost of construction of the prototype platform is approximately $US10 per sensor. A communication protocol was also developed to allow many of these devices to be installed simultaneously and for the transmission of collected data and dynamic configuration and reprogramming. A receiver system allows for the collation and presentation of collected data. Low cost soil moisture sensors were coupled to the platform and installed in a commercial nursery wholesaler. Field trials of the network were successfully conducted.


Entanglement is sometimes regarded as the quintessential measure of the quantum nature of a system and its significance for the understanding of coupled electronic and vibrational motions in molecules has been conjectured. Previously, we considered the entanglement developed in a spatially localized diabatic basis representation of the electronic states, considering design rules for qubits in a low-temperature chemical quantum computer. We extend this to consider the entanglement developed during high-energy processes. We also consider the entanglement developed using adiabatic electronic basis, providing a novel way for interpreting effects of the breakdown of the Born-Oppenheimer (BO) approximation. We consider: (i) BO entanglement in the ground-state wavefunction relevant to equilibrium thermodynamics, (ii) BO entanglement associated with low-energy wavefunctions relevant to infrared and tunneling spectroscopies, (iii) BO entanglement in high-energy eigenfunctions relevant to chemical reaction processes, and (iv) BO entanglement developed during reactive wavepacket dynamics. A two-state single-mode diabatic model descriptive of a wide range of chemical phenomena is used for this purpose. The entanglement developed by BO breakdown correlates simply with the diameter of the cusp introduced by the BO approximation, and a hierarchy appears between the various BO-breakdown correction terms, with the first-derivative correction being more important than the second-derivative correction which is more important than the diagonal correction. This simplicity is in contrast to the complexity of BO-breakdown effects on thermodynamic, spectroscopic, and kinetic properties. Further, processes poorly treated at the BO level that appear adequately treated using the Born-Huang adiabatic approximation are found to have properties that can only be described using a non-adiabatic description. For the entanglement developed between diabatic electronic states and the nuclear motion, qualitatively differently behavior is found compared to traditional properties of the density matrix and hence entanglement provides new information about system properties. For chemical reactions, this type of entanglement simply builds up as the transition-state region is crossed. It is robust to small changes in parameter values and is therefore more attractive for making quantum qubits than is the related fragile ground-state entanglement, provided that coherent motion at the transition state can be sustained.


Over the past decade, government trade and finance ministries have increasingly turned toward negotiating bilateral and regional trading arrangements, and away from negotiations in multilateral forums like the WTO. There are several reasons for this shift, including changes in the global political environment and negotiating obstacles encountered by the multinational business community at the multilateral level. This shift appears to be an embedded phenomenon. Positive and negative aspects of preferential trading arrangements (PTAs) are in evidence. Trade creation-trade diversion economic analysis suggests the results may be net global welfare enhancing, although such analysis does not readily assess distributional effects. The global economy is enjoying a period of sustained and widely distributed economic growth, suggesting that the PTA phenomenon is not an immediate economic threat. On the negative side, the PTAs lead to administrative complexity, and may be somewhat destabilizing as businesses are encouraged to relocate. Some countries may suffer if left out, but this risk is ameliorated by the wide availability of potential negotiating partners. The PTA negotiating environment strongly favors powerful economic actors like the United States and European Union, which are largely dictating terms to developing (and developed) countries. Developing countries, particularly the less economically powerful, are losing autonomous decision-making authority. The consequences of this are difficult to quantify, and may raise questions better attuned to moral philosophers than economists. The WTO continues on its way, relegated to a less central status. A return to the WTO might reinvigorate the role of less powerful actors, but such return does not appear an immediate prospect. The PTA phenomenon, on balance, does not appear aggressively threatening. We may, however, be underestimating the positive role of multilateralism. , Oxford University Press.


Background and objectives: Discoid meniscus injury is a rare form of abnormal meniscus morphology with unknown pathogenesis. The complete disc-shaped meniscus is more prone than incomplete disc-shaped meniscus to tearing and adverse reactions such as joint degeneration and osteochondritis. Moreover, its clinical efficacy is not satisfactory. Arthroscopic meniscus surgery can enhance the stability of the meniscus and provide sufficient cushioning pressure to prevent recurrent meniscal tears. Therefore, this study will investigate the efficacy of arthroscopic surgery for discoid meniscus injury in knee joint and analyze risk factors that influence the efficacy of arthroscopic surgery. Methods: This single-center, self-control study will include 196 patients with discoid meniscus injury who will receive arthroscopic meniscus repair (Stryker) from December 2018 to December 2019 at the Department of Sports Trauma and Arthroscopy, First Affiliated Hospital of Anhui Medical University of China. This surgical procedure will include meniscus plasty and subtotal meniscectomy. After surgery, all included patients will be followed up for 6–18 months. Surgical efficacy will be evaluated by Lysholm score. Patients will be divided into an excellent-and-good group (Lysholm score ≥ 85) and a poor group (Lysholm score Results: The primary outcome measure of this study is the change in excellent-and-good rate of Lysholm score that reflects knee joint function measured at the last follow-up in patients undergoing arthroscopic meniscus surgery. Secondary outcome measures are Lysholm score; Outerbridge grade of chondral lesion; knee joint morphology by magnetic resonance images before surgery and at the last follow-up; age, sex, lesion region, and course of disease before surgery; and incidence of adverse reactions at the last follow-up. Clinical data from 115 patients with discoid meniscus injury (150 knees) who received treatment from April 2015 to September 2016 were retrospectively analyzed. Six to eighteen months of follow-up of 115 patients revealed a significant difference in Lysholm scores before surgery (65.80 ± 9.39) and at the last follow-up (89.15 ± 7.45; P Conclusion: Results from this study hope to confirm that arthroscopic surgery for discoid meniscus injury is a definitive treatment technique. Patient age and the degree of chondral lesion are closely related with efficacy, so it is recommended that patients with symptomatic discoid meniscus injury undergo surgery as soon as possible. Ethics and trial registration: This study was approved by the Medical Ethics Committee, First Affiliated Hospital of Anhui Medical University (approval No. PJ2018-02-03) on February 5, 2018. The version of the study protocol is 1.0. Patients and their family members will volunteer to participate in this study. Written informed consent will be obtained from each patient. This study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800019182) on October 30, 2018.


Discursive psychologists (Edley, 2001; Potter & Wetherell, 1987; Wetherell, 1998) have analysed identity work in talk, including the ways in which understandings which prevail in a wider social context are taken up or resisted as speakers position themselves and are positioned by others. In these terms, a narrative is generally understood in two ways. The first is as an established understanding of sequence or consequence, such as a potential life trajectory, which becomes a discursive resource for speakers to draw on (cf. Bruner's 'canonical narratives', 1991). The second is of a narrative as a situated construction, such as the biography produced by a speaker within a particular interaction. In this article, I propose an expanded analytic focus which considers how the versions of a biographical narrative produced in previous tellings become resources for future talk, thus setting constraints on a reflexive speaker's work to construct a coherent identity across separate interactions and contexts (Taylor & Littleton, forthcoming).


ABSTRACT Inevitably, there are a great number of methodological challenges and limitations to estimating the extent of human trafficking, which are largely due to definitional issues and the hidden nature of the trafficked population. To date, most national and global estimates of the problem have been discredited for using flawed, nontransparent, or nonexistent research methods; however, researchers have previously suggested that methodologies from public health, including those used to estimate hidden and transient populations, might also be useful to estimate the trafficked population. Specifically, research design, sampling strategies, and measures commonly used to estimate hidden populations in public-health research may hold promise for future human-trafficking studies, reducing bias and resulting in more narrow and precise range estimates of victims. This article presents examples of studies using public-health research methods to estimate various hidden and stigmatized populations (e.g., injection drug-users, homeless and runaway youth) and proposes a set of strategies that might be considered for future prevalence studies on human trafficking. Recent prevalence studies on human trafficking that have successfully implemented public-health research methods, such as Respondent-Driven Sampling and Venue-Based Sampling, are also discussed.


BACKGROUND Patients with untreated obstructive sleep apnoea (OSA) have increased motor vehicle collisions (MVCs). When successfully treated, they report improved driving and fewer mishaps, but there are few objective data to confirm this. A study was therefore undertaken to examine actual MVC data in a large group of patients with OSA before and after treatment with continuous positive airway pressure (CPAP) compared with a control group matched for age, sex, and type of driver's licence (commercial or non-commercial). METHODS Two hundred and ten patients of mean (SD) age 52 (11) years, body mass index (BMI) 35.5 (10) kg/m2, apnoea/hypopnoea index (AHI) 54 (29) events/h were treated with CPAP for at least 3 years. MVC records were obtained from the Ontario Ministry of Transportation (MTO) database for patients and an equal number of randomly selected control drivers. MVC rates were compared for 3 years before and after CPAP therapy for patients and for the corresponding time frames for controls. RESULTS Untreated patients with OSA had more MVCs than controls (mean (SD) MVCs/driver/year 0.18 (0.29) v 0.06 (0.17), p<0.001). Following CPAP treatment the number of MVCs/driver/year fell to normal (0.06 (0.17)) while, in controls, the MVC rate was unchanged over time (0.06 (0.17) v 0.07 (0.18), p=NS). Thus, the change in MVCs over time between the groups was very significant (change = –0.12 (95% CI –0.17 to –0.06), p<0.001)). The MVC rate in untreated patients (n=27) remained high over time. Driving exposure was not different following CPAP. CONCLUSIONS The risk of MVCs due to OSA is removed when patients are treated with CPAP. As such, any restrictions on driving because of OSA could be safely removed after treatment.


Vicky Duckworth and Jonathan Tummons co-authored the book "Contemporary Issues in Lifelong Learning" published in 2010 by McGraw-Hill Educational Publications in the UK. With a preface and eight chapters, the book brings readers a critical analysis of contemporary issues and debates in the lifelong learning sector. The topics discussed in the book are presented in an easily understandable format. The authors examine topics such as inclusive practices, employment agenda, curriculum, and research-led instruction that are important for the lifelong learning sector. There are practical strategies and reflective tasks in the book to help readers become better practitioners with a critical and inquisitive point of view. At the beginning of each chapter, learning outcomes, case studies, chapter summaries, and useful web sites, that are important for trainees, teachers, and stakeholders in continuing professional development programs, are presented.


We quantified herbivory on leaves of two mangrove species, Rhizophora mangle and Avicennia germinans, at eight sites in Belize. Amounts and types of damage were compared among three mainland sites and five mangrove cays off the coast. Several environmental and autecological factors that potentially influence herbivory were examined, including canopy cover, tree age, leaf age, tidal height, and nutrient enrichment. Herbivores damaged 4.3 percent to 25.3 percent of Rhizophora leaf area and 7.7 percent to 36.1 percent of Avicennia leaf area, figures comparable to other mangal throughout the world. On average, Avicennia was less frequently damaged than Rhizophora at all sites but one. Herbivory at a bird rookery was not significantly higher than elsewhere, indicating that nutrient enrichment of leaves did not stimulate herbivory at this site. Significant but inconsistent differences in damage were detected between the cays and mainland sites. Significant differences, dependent on tidal height, were found between seedlings and trees. Rhizophora seedlings growing under a canopy of adult conspecifics suffered twice as much damage as seedlings growing in areas where the adult canopy was removed. Damage types occurring on each species were consistent across all sites, but the two species did not share the same herbivores.


Background The proliferation signal inhibitors (PSIs) sirolimus (SRL) and everolimus (ERL) are the potent immunosuppressive drugs using in organ transplantation and has been used successfully in renal transplant recipients (RTX) as well. PSIs are the key factors to overcome the allograft rejections after successful organ transplantation since the immune system starts to react against the graft. SRL and ERL prevents the action of immune system b inhibits the proliferation of Tand B-cells by inhibiting the intracellular signaling of interleukin-2. The presence of excess amount of serum proteins including albumin in the urine is considered as proteinuria, which reflects the loss of kidney function. The occurrence of proteinuria can be the result of abnormal glomerular filtration and/or impaired tubular endocytic function of renal proximal tubular epithelial cells (PTECs). Megalin and cubulin are two scavenger receptors present on epical surface of PTECs and involved in reabsorption of proteins after glomerular ultrafiltration process in the kidney. Proteinuria appears too high in renal transplanted patients during ongoing treatment with PSIs. Aim Our study aimed to investigate and correlate the expression level of megalin and cubilin and albumin uptake in PTEC of renal transplanted patients before and after conversion to PSI. Methods To retrieve the maximal expression of our interest molecules in renal PTECs, we optimized antigen retrieval (AR) method and primary antibody dilution for each molecule separately. An optimization experiment was performed on 3 different normal patients renal biopsies were used. Later, human renal biopsy specimens originated from 4 different renal transplanted patients were used in this study. From all the 4 patients biopsy specimens were taken before and ongoing administration of PSIs (SRL, ERL). The expression of megalin, cubilin and albumin uptake in PTEC of renal transplant patients was determined by immunohistochemical staining. Results Based on the optimization experiments, we selected the AR method and primary antibody dilution for the expression of megalin, cubilin and albumin uptake. In 4 renal transplanted patients following administration of PSIs results in patients 1, 2, 3 expression of megalin, cubilin and albumin uptake during ongoing PSI treatment was not comparable or even more intense than before PSIs introduction. The expression of megalin, cubilin and albumin uptake was reduced in patient 4 during ongoing PSI treatment. Conclusion Our findings suggest that the renal transplant patient 4 developed proteinuria during PSI medication. The expression of megalin, cubilin and albumin uptake was markedly decreased during ongoing PSI treatment in patient 4. We concluded that there is a direct link between PSI medication and tubular dysfunction, which might cause proteinuria


To characterize trace metal cycling in marine systems as mediated by heterotrophic pro- tists, we conducted a series of laboratory experiments in 2-organism model systems consisting of bac- teria and protistan grazers. Trace metal isotopes ( 59 Fe and 234 Th), 14 C, and bulk organic carbon mea- surements were used to follow the chemical transformation of bacterial carbon and associated trace metals by several different grazer species. Results indicate that grazers were able to cause reparti- tioning of Th and regeneration of Fe from bacterial prey into the dissolved phase (<0.2 µm), even in particle-rich laboratory cultures. For both Th and Fe, protist grazing led to the formation of relatively stable dissolved and colloidal metal-organic species. Metal/carbon ratios of the particle pool in some model systems with grazers were significantly altered, indicating a decoupling of trace metal and organic carbon cycling through the grazing process. Different protist species exhibited substantial variation (up to a factor of 10) in their ability to quantitatively remobilize trace metals from bacterial prey. The implications of these findings for trace metal cycling in marine systems are discussed.


There has been much discussion in the literature regarding the determinants of ribosomal decoding speed during the mRNA translation process. Computational results based on mechanistic models for ribosomal kinetics have predicted a major role for near-cognate and non-cognate tRNA binding competitive behavior on translation elongation rate. In contrast, a recent experimental study proposed the difference between Watson-Crick and non-Watson-Crick type of tRNA decoding as the main determinant of translation speed. We model stochastically the translation process using a mechanistic model for ribosomal kinetics that accounts for both competitive tRNA behavior and Watson-Crick and non-Watson-Crick types of decoding. With this framework we identify the relative roles that tRNA binding competition and decoding interaction type play on translation elongation rate, and we explore the conditions that allow for optimal protein synthesis.


Summary Leptospirosis is a zoonosis of worldwide distribution, caused by Leptospira interrogans. It is a well known cause of bovine reproductive losses such as abortion, infertility, stillbirth and birth of weak calves. In this research, the relationship between the seroprevalence rate of Leptospira spp. infection and abortion in industrial dairy farms of Hamedan province, Iran was studied. A total of 80 blood samples were taken from aborted cows in six dairy farms. Sera were tested for antibodies against 6 serovars of Leptospira interrogans (hardjo, pomona, canicola, grippotyphosa, icterohaemorrhagiae and ballum) using microscopic agglutination test (MAT). Antibodies were detected in 18 (22.5%) of the aborted cows, including 17 (21.25%) against L. canicola and 1 (1.25%) against L. pomona. It is concluded that dogs (shepherd and stray) and wild carnivores may have an important role to maintain and transmit the L. canicola infection to the cattle population in this region, therefore, vaccination of cattle and shepherd dogs should be applied.


Laughter is a very interesting non-verbal human vocalization. It is classified as a semi voluntary behavior despite being a direct form of social interaction, and can be elicited by a variety of very different stimuli, both cognitive and physical. Automatic laughter detection, analysis and classification will boost progress in affective computing, leading to the development of more natural human-machine communication interfaces. Surface Electromyography (sEMG) on abdominal muscles or invasive EMG on the larynx show potential in this direction, but these kinds of EMG-based sensing systems cannot be used in ecological settings due to their size, lack of reusability and uncomfortable setup. For this reason, they cannot be easily used for natural detection and measurement of a volatile social behavior like laughter in a variety of different situations. We propose the use of miniaturized, wireless, dry-electrode sEMG sensors on the neck for the detection and analysis of laughter. Even if with this solution the activation of specific larynx muscles cannot be precisely measured, it is possible to detect different EMG patterns related to larynx function. In addition, integrating sEMG analysis on a multisensory compact system positioned on the neck would improve the overall robustness of the whole sensing system, enabling the synchronized measure of different characteristics of laughter, like vocal production, head movement or facial expression; being at the same time less intrusive, as the neck is normally more accessible than abdominal muscles. In this paper, we report laughter discrimination rate obtained with our system depending on different conditions.


The ability of non-equilibrium plasmas to modify surfaces has been known for many years. And a promising way to perform surface modifications without altering the bulk properties is plasma polymerization since this technique is versatile and can be applied to a wide range of materials. Plasma polymer films usually show good biocompatibility when compared to classical biomaterials. The possible biomedical use of plasma polymers motivates the study of their behavior during storage and in aqueous environment. Therefore, it is of major importance to understand the change of properties of these plasma polymers over time and when in contact with certain fluids. Recently, plasma polymer gradients (surfaces that display a change in at least one physicochemical property over distance) have attracted significant attention from the biomedical filed where the interaction of cells with a material surface is of major interest. This chapter discusses biomaterial functionalization via plasma polymerization focusing on their use in the biomedical field as well as their aging and stability behaviors. Plasma polymer gradients as valuable tools to investigate cell-surface interactions will also be reviewed.


In this issue of the Hastings Center Report, Tony Hope, Jacinta Tan, Anne Stewart, and Ray Fitzpatrick, reporting on twenty-nine interviews they conducted with women with so-called anorexia nervosa, note that the participants recurrently raised issues of authenticity. The paper reflects on the way their behaviors, experiences, and choices can be considered authentic (parts of their "real selves"), or inauthentic (parts of their anorexia). The authors also pose a question about the normative implications of their analysis—if some choices are inauthentic, then is it ethical to override them? For example, they suggest that "showing respect" for the sufferer "does not necessarily mean simply acceding to the person's requests to decline help or treatment." The paper is rich in suggestions and hypotheses and raises a number of questions, some methodological and others more "substantial." I will discuss only a couple of issues. On the methodological front, the authors' assumptions about anorexia are never made explicit, and this can bias the respondents' answers. The authors ask, for instance, "What is your understanding of what anorexia nervosa is?" "How has anorexia nervosa changed you"? and "Do you think anorexia is an illness?" In doing so, they assume that anorexia is a thing with the power to change people or cause behaviors. Thus rather than just ask a question, they provide an answer. One wonders whether the respondents' stress on authenticity is a function of the interviewers' perspective. What would the respondents have answered had they been asked questions such as, "How and when have you changed (if you have changed)?" rather than, "How has anorexia changed you?" "What is your understanding of your values, fears . . . ?" rather than, "What is your understanding of anorexia?" Of course, the interviewers cannot be expected to approach a subject without preconceptions and opinions about it. But it is important that these are spelled out clearly, especially because the relationship between researcher and participant is not on a par; the researcher is "the expert," and the sufferer, as the vulnerable party, may not be in the position to detect and critically evaluate the interviewer's hidden assumptions. Therefore, if, as the authors emphasize, it is important to remember the value of self-knowledge, as the Oracle of Delphi they cite advised, then it is perhaps even more important to remember Pyrrho's lesson, on the importance of skepticism and of suspending judgment as a means to attain knowledge. On a more substantial point, the authors (rightly) stress the importance of self-knowledge, but knowing and understanding are different: I may know that fat terrifies me and yet have no understanding of why. I may even predict that Sally will make herself sick after dinner, and still fail to understand why. Knowledge and ability to predict may be mistaken for understanding and for the ability to explain, and the authors seem to make such a mistake. They suggest that some behaviors or experiences may not be authentically a part of the sufferers' self, but rather caused by the anorexic side. In fact, they note that a recurrent theme in interviews is the "power struggle" between these different parts. This perspective may be reassuring (I am not doing this to myself, something is doing this to me), but it can be dangerous. "Pro-Ana" websites exist thanks to such reification: anorexia becomes "the best friend" or the worthwhile goal. Moreover, this approach may disempower some sufferers: if anorexia is something that happens to me, what can I do about it? And if the therapists themselves consider anorexia as an inauthentic and self-destructive force, then how can they propose to truly understand the sufferer's experiences? The sufferers are those with the real expertise: they are in the position to tell us why thinness and lightness are so important to them, what they symbolize, and why fat is dangerous. Values such as self-control, perfectionism, mastery of the body, and will-power have already been identified in the literature as among the core features that may explain the terror of fat and the relentless search for thinness. In Western morality, corpulence has traditionally symbolized vices such as indolence and lack of strength of character. In order to understand anorexia, the phenomenon must be examined in its various facets; in order to comprehend it, we should question not only our own beliefs about anorexia, but also the values that may underlie it, and be prepared to investigate the continuity between the set of values that inspire the search for lightness and the set of values that shape our own responses to thinness. Anorexia, Authenticity, and the Expert Perspective


Human amniotic membrane-derived mesenchymal stem cells (hAM-MSCs) are capable of differentiating into several lineages and possess immunomodulatory properties. In this study, we investigated the soluble factor-mediated immunomodulatory effects of hAM-MSCs. Mitogen-induced peripheral blood mononuclear cell (PBMC) proliferation was suppressed by hAM-MSCs in a dose-dependent manner as well as hAM-MSC culture supernatant. Moreover, interferon-gamma and interleukin (IL)-17 production significantly decreased from PBMC, whereas IL-10 from PBMCs and transforming growth factor beta (TGF-β) production from hAM-MSCs significantly increased in co-cultures of hAM-MSCs and PBMCs. Production of several MSC factors, including hepatocyte growth factor (HGF), TGF-β, prostaglandin E2 (PGE2), and indoleamine 2, 3 dioxygenase (IDO), increased significantly in hAM-MSCs co-cultured with PBMCs. These results indicate that the immunomodulatory effects of hAM-MSCs may be associated with soluble factors (TGF-β, HGF, PGE2, and IDO), suggesting that hAM-MSCs may have potential clinical use in regenerative medicine.


The level of aggregate excess reserves held by U.S. depository institutions increased significantly at the peak of the 2007–2009 financial crisis. Although the amount of aggregate reserves is determined almost entirely by the policy initiatives of the central bank that act on the asset side of its balance sheet, the motivations of individual banks in accumulating reserves differ and respond to the impact of changes in the economic environment on individual institutions. We undertake a systematic analysis of this massive accumulation of excess reserves using bank-level data for more than 7000 commercial banks and almost 1000 savings institutions during the U.S. financial crisis. We propose a testable stochastic model of reserves determination when interest is paid on reserves, which we estimate using bank-level data and censored regression methods. We find evidence primarily of a precautionary motive for reserves accumulation with some notable heterogeneity in the response of reserves accumulation to external and internal factors of the largest banks compared with smaller banks. We combine propensity score matching and a difference-in-differences approach to determine whether the beneficiaries of the Capital Purchase Program of the Troubled Asset Relief Program accumulated less cash, including reserves, than non-beneficiaries. Contrary to anecdotal evidence, we find that banks that participated in the program accumulated less cash, including reserves, than nonparticipants in the initial quarters after the capital injection.


Human enterovirus 71 (EV71) is an important human enterovirus which belongs
to the Enterovirus genus of the Picornaviridae family. Large outbreaks of EV71
have been associated with severe central nervous disease (CNS) manifestations
including the hand, foot and mouth disease (HFMD). To date, there is no
effective antiviral drug available to treat the infections. Therefore, the
development of an effective vaccine is considered as one of the best choice to
prevent the diseases caused by EV71.
The VP1 protein which is the most immunogenic capsid protein of EV71, can be
used in the development of subunit EV71 vaccines. The complete VP1 protein of
EV71 was truncated into six regions and fused to the full length nucleocapsid
protein (NPfl) and truncated NP (NPt; which lacks 20% amino acids from its Cterminal
end). Western blot analysis using rabbit anti-VP1 serum showed that the
N-terminal region of the VP1 protein contained a major antigenic region. Of all
the recombinant NP proteins, the ones carrying truncated VP1 protein, VP11-100
were efficiently expressed in Escherichia coli system. Electron microscopic
analysis of the purified NPt-VPl-loo revealed that this protein predominantly selfassembled
into intact ring-like structure whereas NPfl-VPl-loo showed disrupted
ring-like formations. Rabbits immunized with these purified recombinant proteins
exhibited a strong immune response against the complete VP1 protein. The
antisera of these recombinant proteins also reacted positively with the authentic
EV71 when analyzed by an immuno flourescence assay thus suggesting their
potential as subunit vaccine candidates against EV71 infections and also as
immunological reagents for the detection of anti-EV71 antibodies in serum
samples.


Is it possible to abstract a formal mechanism originating schisms and governing the size evolution of social conversations? In this work a constructive solution to such problem is proposed: an abstract model of a generic N-party turn-taking conversation. The model develops from simple yet realistic assumptions derived from experimental evidence, abstracts from conversation content and semantics while including topological information, and is driven by stochastic dynamics. We find that a single mechanism namely the dynamics of conversational party's individual fitness, as related to conversation size controls the development of the self-organized schisming phenomenon. Potential generalizations of the model including individual traits and preferences, memory effects and more elaborated conversational topologies may find important applications also in other fields of research, where dynamically-interacting and networked agents play a fundamental role.


Over the past 200 years, humans have dramatically altered our global environmental envelope accidentally through uncontrolled greenhouse gas emissions. Humans have also developed the technology to both stop emitting greenhouse gases and ultimately to remove them from the atmosphere through a combination of natural and engineered pathways. Ultimately, humanity must practice CO2 removal in addition to maximal reduction in greenhouse gas emissions through conventional mitigation to achieve net-zero greenhouse gas emissions and ultimately net-negative emissions. To accomplish this task will require enormous sums of money and substantial cooperation between groups of people who commonly do not work together: technical experts, financiers, and government officials. In addition to heightened and accelerated ambition, humility is required as well. The task requires frequent and extended achievement in arenas that many scientists and engineers commonly understand only tangentially (e.g., lawmaking, regulatory enforcement, and project finance).


We suggest new decoding techniques for diversity channels employing space time codes (STC) when the channel coefficients are unknown to both transmitter and receiver. Most of the existing decoders for unknown diversity channels employ training sequence in order to estimate the channel. These decoders use the estimates of the channel coefficients in order to perform maximum likelihood (ML) decoding. We suggest an efficient implementation of the generalized likelihood ratio test (GLRT) algorithm that improves the performance with only slight increase in complexity. We also suggest an energy weighted decoder (EWD) that shows additional improvement without further increase in the computational complexity.


It has been determined that the cause of the non-linear effect manifestation during Newtonian fluids flows as well as strengthening of the anomalous phenomena of non-Newtonian fluids in microcapillary cracks is value of crack opening. Non-Newtonian properties are manifested in the system of crack-fluid during viscous fluids flow into cracks with h  hcr opening, non-Newtonian properties are increased for anomalous fluids but these effects are absent at h > hcr. These effects occur in the crack-fluid system only at h  hcr. It has been determined experimen-tally that after fluids seepage from the crack, the above-mentioned effects are absent. The obtained microcracked effect for homogene-ous fluid purified from air or gas is an analog of Jamin effect and it is called as microcracked fluid effect. This effect can increase still further Jamin effect at two-three phase systems of fluids flow in microcrack. The critical values of the crack opening have been determined wherein the above-mentioned changes in the fluids properties are practically disappeared. The stimulation methods and bottom-hole zone due to powerful energy fields of oil-and-gas fields with fractured rocks should promote increasing the cracks opening of the oil-and-gas fields of the viscous and anomalous oils. DOI: http://dx.doi.org/10.5755/j01.mech.21.1.10128


Chronic pain is a major clinical problem. Target-derived growth factors have been implicated in the initiation and maintenance of persistent pain states. Artemin, a member of the glial cell line-derived neurotrophic factor (GDNF) family, binds to its GPI-anchored receptor, GFRa3, and initates intracellular signaling via the tyrosine kinase, Ret. Expression of the GFRa3 receptor is largely restricted to the peripheral nervous system and is found in a subpopulation of nociceptive sensory neurons of the dorsal root and trigeminal ganglia (DRG & TG) that coexpress the Ret and TrkA receptor tyrosine kinases and the thermosensitive channel TRPV1. To investigate the role of artemin in regulating nociceptor properties and function, we isolated transgenic mice that overexpress artemin in keratinized tissues (ART-OE). Expression of artemin increased DRG neuron number, confirming the survival promoting effects of artemin. In addition, ART-OE mice had increased mRNA encoding GFRa3, TrkA, TRPV1 and the putative noxious cold and mustard oil detecting channel, TRPA1. Immunolabeling showed that nearly all GFRa3-positive neurons expressed TRPV1 and most of these neurons were also TRPA1-positive. Somas of GFRa3/TRPV1-positive neurons in the ART-OE mice were hypertrophied and there was increased staining for these proteins in the periphery. Interestingly, increases in TRPV1 and TRPA1 mRNA were more robust in TG than DRG. Because of these differential effects, lingual afferents innervating the heavily keratinized tongue were also examined. Retrogradely-labeled lingual afferents from ART-OE tongues showed an increased percentage of GFRa3- and TRPV1-positive neurons. Behavior analysis showed that these anatomical changes were correlated with increased sensitivity to noxious heat, noxious cold, capsaicin and mustard oil applied to the hindpaw, as well as oral sensitivity to capsaicin and mustard oil placed in the drinking water of these mice. Functional analysis of dissociated sensory neurons using calcium imaging showed hypersensitivity to capsaicin and mustard oil in trigeminal neurons isolated from ART-OE mice, and even greater sensitivity in the lingual subpopulation. Taken together, these results indicate that artemin promotes the survival and modulates functional properties of a select population of TRPV1- and TRPA1-positive nociceptors critical for the detection of noxious thermal and chemical stimuli in both cutaneous and lingual systems.


Injections of parathyroid hormone (PTH) have been reported to stimulate skeletal accretion through increased bone formation in several species, and osteoblast proliferation is a critical component of bone formation. However, the biological mechanisms of PTH‐stimulated bone cell proliferation are largely unknown. In this study, we demonstrated that PTH stimulates proliferation of the osteoblast precursor cell line, TE‐85, in association with increasing cdc2 protein levels and its kinase activity. cdc2 antisense oligonucleotides blocked PTH‐induced DNA synthesis and cell cycle progression. Analysis of the time course of PTH‐stimulated cdc2 message levels demonstrated that cdc2 mRNA levels were increased 1.5‐ to 4‐fold between 3–18 h following release from cell synchronization. Transfections of TE‐85 cells with a series of cdc2 promoter‐luciferase deletion constructs revealed PTH stimulation of the cdc2 promoter. Promoter constructs containing a mutation in the E2F binding site were not stimulated by PTH. Gel mobility shift assays demonstrated increased free E2F levels in TE‐85 nuclear extracts in response to PTH. Furthermore, the ratios of hyperphosphorylated to hypophosphorylated forms of Rb protein were increased by PTH treatment. These results demonstrate that PTH‐stimulated cdc2 expression was associated with TE‐85 cell proliferation and that the mechanism of stimulating cdc2 gene expression involved increasing the levels of free E2F.


MOUSSONIA LARRYSKOGII (GESNERIACEAE), A NEW SPECIES FROM OAXACA AND VERACRUZ, MEXICO, IS DESCRIBED. THIS SPECIES RESEMBLES MOUSSONIA STRIGOSA (C. V. MORTON) WIEHLER, FROM COSTA RICA, BUT DIFFERS MAINLY IN THE VILOSE PUBESCENCEWITH ADPRESSED TRICHOMES ALMOST THROUGHOUT THE ENTIRE PLANT, 2 OR 3 LEAVES PER NODE, LOWER SURFACE OF THE LEAF NOT BULLATE, BRANCHED INFL ORESCENCE A COMPOUND CYME, NOT UMBELLIFORM, TUBULAR FL OWER, AND THE OBCONIC TUBE OF THE CALYX. POSSIBLE NATURAL HYBRID BETWEEN THIS SPECIES AND MOUSSONIA HIRSUTISSIMA IS PRESENTED.


Abstract The role of plasma membrane-localized sucrose transporter (NtSUT1) was investigated using cultured tobacco cell (Nicotiana tabacum L.) line BY-2. The wild type (WT) cells were first transformed with the NtSUT1 gene or its fragments cloned from tobacco cell line SL to form the over-expression (OX) and suppression (RNAi) cell lines, respectively. Using OX and RNAi transgenics, the role of NtSUT1 in growth capacity of actively growing cells and in aluminum (Al)-treated cells was examined. During the logarithmic phase of growth in nutrient medium containing 2,4-dichlorophenoxyacetic acid (2,4-D), both the rate of sucrose uptake measured with radio-tracer and the content of soluble sugars were higher in OX and lower in RNAi cell lines compared to WT. Overall, the content of soluble sugars negatively correlated with the time necessary for doubling mass (fresh weight). When cells were treated without (control) or with Al in a simple medium containing calcium, sucrose and 2-(N-morpholino)ethanesulfonic acid (MES; pH 5.0) for up to 18 h, the expression of NtSUT1 under its native promoter, or under the control of strong constitutive cauliflower mosaic virus (CaMV) 35S promoter, was strongly dependent on the presence of 2,4-D. Thereafter, the cells were preferentially treated in the presence of 2,4-D. During 6 h after a start of the control treatment, sucrose uptake rates were, compared to WT, slightly higher and lower in OX and RNAi lines respectively. The addition of Al reduced the sucrose uptake rates of OX and WT to the level of RNAi line, indicating that Al inhibits sucrose uptake via NtSUT1. During the post-Al culture of control and Al-treated cells in a nutrient medium, sucrose uptake rates were much higher in OX compared to WT and RNAi lines, which closely and positively correlated with the growth capacity of the cells. Judging from the growth capacity of Al-treated cells relative to that of control cells, OX cells were more tolerant to Al than WT and RNAi. In summary, we conclude that over-expression of NtSUT1 confers higher growth capacity in actively growing cells as well as in Al-treated cells.


Consider the career of an enduring if controversial icon of American entertainment: the genial circus elephant. In "Entertaining Elephants" Susan Nance examines elephant behavior - drawing on the scientific literature of animal cognition, learning, and communications - to offer a study of elephants as actors (rather than objects) in American circus entertainment between 1800 and 1940. By developing a deeper understanding of animal behavior, Nance asserts, we can more fully explain the common history of all species. "Entertaining Elephants" is the first account that uses research on animal welfare, health, and cognition to interpret the historical record, examining how both circus people and elephants struggled behind the scenes to meet the profit necessities of the entertainment business. The book does not claim that elephants understood, endorsed, or resisted the world of show business as a human cultural or business practice, but it does speak of elephants rejecting the conditions of their experience. They lived in a kind of parallel reality in the circus, one that was defined by their interactions with people, other elephants, horses, bull hooks, hay, and the weather. Nance's study informs and complicates contemporary debates over human interactions with animals in entertainment and beyond, questioning the idea of human control over animals and people's claims to speak for them. As sentient beings, these elephants exercised agency, but they had no way of understanding the human cultures that created their captivity, and they obviously had no claim on (human) social and political power. They often lived lives of apparent desperation.


Purpose: The use of high‐Z nano‐particles (NP) increases the dose in the nearby volume by absorbing more photons of keV energy. The resulting electrons deposit the dose locally. Additionally, Auger electrons are generated. In combination with tumor specific agents such a dose deposition mechanism could provide an efficient methodology to increase dose to microscopic disease. To quantify dose enhancement and spectral changes in the vicinity of these particles we propose the use of GaF‐chromic film which can be analyzed using scanning electron microscopes(SEM) to yield microscopic insight in the processes at hand. Materials Measurements were performed using a clinical RT‐simulator (40kVp). GaF‐chromic active layer only film was coated with a layer of gold NP's of about 30nm thick. The film and its control was irradiated with the NP downstream from the source to a dose of 0.01Gy. The samples were characterized by means of the SEM unit of the FEI Dualbeam Nova 600 Nanolab. The resulting images showed a landscape with a number of tracks which we hypothesize to be electron tracks. The images were processed using a skeletonization technique based on mathematical morphology, yielding the number of tracks and a quantification of the track length. A monte carlo simulation using a 40keV photon beam was performed. Spectral histograms were generated using CSDA tables converting track length to energy. Results :Good agreement between the two histograms exist. The low energy portion of the MC‐simulation fails as electrons with energies lower than 10keV are not tracked. We also see a larger peak at the track length histogram most probably due to the finite resolution of the film. Conclusions: We have shown that GaF‐chromic films can be used to gain insight in the overall dose deposition and enhancement at a microscopic level. Additionally, the spectral information was obtained.


Abstract. This paper aims to quantify the uncertainty in projections of future hydrological extremes in the Biala Tarnowska River at Koszyce gauging station, south Poland. The approach followed is based on several climate projections obtained from the EURO-CORDEX initiative, raw and bias-corrected realizations of catchment precipitation, and flow simulations derived using multiple hydrological model parameter sets. The projections cover the 21st century. Three sources of uncertainty are considered: one related to climate projection ensemble spread, the second related to the uncertainty in hydrological model parameters and the third related to the error in fitting theoretical distribution models to annual extreme flow series. The uncertainty of projected extreme indices related to hydrological model parameters was conditioned on flow observations from the reference period using the generalized likelihood uncertainty estimation (GLUE) approach, with separate criteria for high- and low-flow extremes. Extreme (low and high) flow quantiles were estimated using the generalized extreme value (GEV) distribution at different return periods and were based on two different lengths of the flow time series. A sensitivity analysis based on the analysis of variance (ANOVA) shows that the uncertainty introduced by the hydrological model parameters can be larger than the climate model variability and the distribution fit uncertainty for the low-flow extremes whilst for the high-flow extremes higher uncertainty is observed from climate models than from hydrological parameter and distribution fit uncertainties. This implies that ignoring one of the three uncertainty sources may cause great risk to future hydrological extreme adaptations and water resource planning and management.


Tremendous progress has been made over the last 2 decades to discover and develop approaches to control hepatitis B virus (HBV) infections and to prevent the development of hepatocellular carcinoma using various interferons and small molecules as antiviral agents. However, none of these agents have significant impact on eliminating HBV from infected cells. Currently the emphasis is on silencing or eliminating cccDNA, which could lead to a cure for HBV. Various approaches are being developed including the development of capsid effectors, CRISPR/Cas9, TALENS, siRNA, entry and secretion inhibitors, as well as immunological approaches. It is very likely that a combination of these modalities will need to be employed to successfully eliminate HBV or prevent virus rebound on discontinuation of therapy. In the next 5 years clinical data will emerge which will provide insight on the safety and feasibility of these approaches and if they can be applied to eradicate HBV infections globally. In this review, we summarize current treatments and we highlight and examine recent therapeutic strategies that are currently being evaluated at the preclinical and clinical stage.


Objective: This paper aims to determine the percentage of road crashes resulting in injuries requiring hospital care that are reported to the police and to identify factors associated with reporting such crashes to the police. Design: The data of one of two hospitals in the Road Casualty Information System were matched with the police's Traffic Accident Database System. Factors affecting the police-reporting rate were examined at two levels: the different reporting rates among subgroups examined and tested with χ2 tests; and multiple explanatory factors were scrutinised with a logistic regression model to arrive at the odds ratios to reflect the probability of police-reporting among subgroups. Results: The police-reporting rate was estimated to be 57.5–59.9%. In particular, under-reporting among children (reporting rate = 33.6%) and cyclists (reporting rate = 33.0%) was notable. Discussion: Accurate and reliable road crash data are essential for unveiling the full-scale and nature of the road safety problem. The police crash database needs to be supplemented by other data. In particular, any estimation about the social costs of road crashes must recognise the under-reporting problem. The large number of injuries not reflected in the police crash database represents a major public health issue that should be carefully examined.


Typological research suggests that double negation - the use of two negative markers to denote one negative meaning - is a popular strategy amongst a wide variety of languages. This paper focuses on two types of double negation. The first type, exemplified by Fr. Je ne chante pas 'I don't sing', consists of a discontinuous sentence negator. The second type consists of a sentence negator and a negative indefinite pronoun or adverb as in I don't see nothing . Iconicity is in the first type related to the language change known as Jespersen's Cycle leading towards the double negative structure. The second type is arguably one of two possible strategies to avoid the less iconic use of a negative indefinite pronoun.


A retrospective of National Wildlife Refuge System conservation shows a promising trajectory. The system has overcome persistent neglect to contribute to conservation policy. Haltingly, it has kept pace with conservation science to remain the chief American contribution to large-scale wildlife protection. Early on, it pioneered the use of habitat acquisition to protect imperiled species. More recently, it has begun to implement the cutting-edge ecological mandate to maintain biological integrity, diversity, and environmental health. Perhaps the most meaningful feature of the history of the refuge system is how closely it mirrors the development of conservation policy in the twentieth century. This article reviews the evolution of refuge system management and shows how it reflects the major conservation developments over the past century. It begins by surveying the system with special reference to the Pelican Island National Wildlife Refuge and the Arctic National Wildlife Refuge. The article conducts a historical review of conservation policy developments, with particular emphasis on their legal dimensions. It then discusses the current conservation framework for the refuges, which is a form of ecosystem management. The article concludes by observing the ways in which the national wildlife refuges are now the most important federal lands for demonstrating sustainability and ecosystem management on a large scale.


Despite the growing global acceptance of an individual's right to adequate food and nutrition, and the state's obligation to ensure that all its citizens are free from hunger, 805 million or one in nine people around the world today are still chronically malnourished; the majority live in developing countries. African states have had a particular problem with food insecurity. Food security on the continent has worsened since the 1970s and by the end of the century, the population in Africa is expected to be three times its current level. Hence, food insecurity in Africa will be much more severe than in other parts of the world. Traditionally, there have been three ways in which a country can achieve food security at the national level: domestic production, commercial food imports and food aid. But many developing countries in sub-Saharan Africa heavily rely on food imports to supply the growing demand for food. This study aims to test whether being dependent on imported food constitutes a hindrance to food security and therefore to sustainable development by assessing the agricultural policy of the two countries (Nigeria and Senegal) and analyzing the impact of food import dependency on poverty, which is seen as a measure of sustainable development. After discussing the problem of food security in Africa in detail, I perform several correlation analyses between the level of food imports and the level of poverty. I found that while in Senegal, there was a significant non-lagged relationship, suggesting that food is being imported to address poverty, there were no significant correlations for Nigeria or for a lagged relationship in either country. I therefore conclude that food imports do not cause poverty but that they also do not contribute to alleviating it. Indeed, other factors such as the cost of imported food must be examined to generate a complete picture of the way in which food imports affect development.


Primo Levi's account of life as a concentration camp prisoner falls into two parts. If This Is A Man describes his deportation to Poland and the twenty months he spend working in Auschwitz. The Truce covers his long journey to Italy at the end of the war through Russia and Central Europe. Levi never raises his voice, complains or attributes blame. By telling his story quietly, objectively and in plain language he renders both the horror and the hope of the situation with absolute clarity. Probing the themes which preoccupy all his writing - work love, power, the nature of things, what it is to be human - he leaves the reader drained, elated, apprehensive.


The 2016 US presidential election resulted in the populist Donald Trump becoming the 45th President of the United States. While many observers assume that this reflects a transitory phase of populism in the US, a closer analysis suggests that there will be a structural populist threat for the US, the West and the world economy. There is survey evidence that US voters consider the inequality which has emerged in the US over many years as unacceptable. At the same time the Lindh-McCall survey results show that the relative majority of US voters expect that big companies rather than government will correct this inequality. This is illusory and wishful thinking and will serve to create continued voter frustration for the lower half of households – this refers to the poorer half of US households – and populism could indeed expand on the basis of such frustration for many years to come. The main drivers of rising inequality in the US, namely ICT expansion, financial globalization and the rise of China's exports will continue in the medium term so that US voters' frustration is a structural problem that cannot easily be remedied and that has consequences for transatlantic and global economic relations as well as security policy implications. While the decline of the income share for the lower half of income earners in Western Europe has been rather modest in 1981-2015, the decline of that share in the US has been dramatic, namely from 20% to 13%. The EU is nevertheless threatened by US populism since its political representatives are trying to export their ideology and approach to Italy and other Western continental EU countries. In the UK, a subtle populism is already becoming more apparent under the heading of BREXIT. If the EU27 could defend the model of the Social Market Economy and export this system to Asia and Africa while joining political forces with ASEAN – and possibly China – to defend the multilateral economic order, European impulses could help to contain US populism.


Payment services offered by non-banks have flourished in recent years. The author provides an overview of the different kinds of non-bank retail payments schemes currently available in Canada, illustrating each by focusing on a specific example. Current players in the Canadian marketplace include electronic bill consolidators, such as epost; online payment providers, like PayPal; and pre-funded schemes, such as retailers' gift cards. The author also discusses the main risks associated with each of the schemes, such as bankruptcy, banker, security, market, and liquidity risks. While the author does not undertake a complete analysis of the market failures that may justify regulation of non-bank retail payment services, he does set out a broad framework for considering whether users and providers of these services have the incentives to manage the associated risks. Since any regulatory response, if deemed to be justifiable after a more complete analysis, must be balanced in its approach, some of the costs of regulation in this area are also considered.


Commentary on: Lincoff AM, Nicholls SJ, Riesmeyer JS, et al . Evacetrapib and cardiovascular outcomes in high-risk vascular disease. N Engl J Med 2017;376:1933–42.

High-density lipoprotein (HDL) cholesterol (HDL-C) is a robust predictor of cardiovascular disease (CVD) events; however, research into both rare monogenic HDL disorders and Mendelian randomisation studies of dysfunctional traits associated with HDL-C demonstrate that this biomarker is not involved in the causal pathway for atherosclerosis.1 Small-effect variants in the gene encoding cholesteryl ester transfer protein (CETP) associate with higher HDL-C and lower myocardial infarction rates, whereas large-effect variants associate with reduced survival. CETP loss-of-function variants also associate with low levels of low-density lipoprotein (LDL) cholesterol (LDL-C), which confounds the attribution of the atheroprotective effect of CETP-mediated HDL changes.

Small molecules that inhibit CETP activity have been previously investigated in two randomised clinical trials of CVD outcomes.2 3 Treatment with torcetrapib, in combination with atorvastatin increased HDL-C …