A ROADMAP FOR DEVELOPMENT OF NOVEL ANTIPSYCHOTIC AGENTS BASED ON A RISPERIDONE SCAFFOLD By Urjita H. Shah, Ph. D. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2017 Major Director: Dr. Richard A. Glennon, Ph. D. Professor and Chairman, Department of Medicinal Chemistry Schizophrenia is a chronic psychotic illness affecting ~21 million people globally. Currently available antipsychotic agents act through a dopamine D2 receptor mechanism, and produce extrapyramidal or metabolic side effects. Hence, there is a need for novel targets and agents. The mGlu2/5-HT2A receptor heteromer has been implicated in the action of antipsychotic agents, and represents a novel and attractive therapeutic target for the treatment of schizophrenia. A long-term goal of this project is to synthesize bivalent ligands where a 5HT2A receptor antagonist is tethered to an mGlu2 PAM via a linker. The goals of the investigation were to study the SAR of risperidone (an atypical antipsychotic agent) at 5-HT2A receptors using a "deconstruction-reconstructionelaboration" approach to determine the minimal structural features of risperidone that contribute to its 5-HT2A receptor affinity and antagonism, and to determine where on the "minimized risperidone" structure an mGlu2 PAM can be introduced. Additional goals included studying the binding modes of various mGlu2 PAMs and identifying where on an mGlu2 PAM a risperidone "partial" structure could be introduced. Biological studies of deconstructed/elaborated analogs of risperidone suggest that the entire structure of risperidone is not necessary for 5-HT2A receptor affinity and antagonism, and that a fluoro group contributes to 5-HT2A binding. 6-Fluoro-3-(4-piperidinyl)-1,2benz[d]isoxazole that has only half the structural features of risperidone retains 5-HT2A receptor affinity and antagonist activity, and represents the "minimized risperidone" structure with the piperidine nitrogen atom representing a potential linker site for eventual construction of bivalent ligands. Molecular modeling studies at 5-HT2A receptors suggest that risperidone and its analogs have more than one binding mode. Modeling studies to evaluate binding modes of various PAMs at mGlu2 receptors, coupled with known SAR information, were used to identify a PAM (JNJ-40411813), and the pyridone nitrogen atom of JNJ-40411813 as a potential linker site. Additionally, potential synthetic routes for JNJ-40411813 were explored that might be of value in the synthesis of bivalent ligands. Based on the structural features of 6-fluoro-3-(4-piperidinyl)-1,2-benz[d]isoxazole, a new pharmacophore for 5-HT2A receptor antagonists, consisting of one aromatic region, a basic protonated amine and hydrogen bond acceptors, has been proposed.


Patients with chronic kidney disease (CKD) are particularly susceptible to cardiovascular complications, and cardiovascular disease (CVD) accounts for more than 50% of all deaths in this population. Cardiac diseases are independently associated with a deterioration of renal function and worsening of existing kidney disease. On the other hand, chronic kidney disease is an independent risk factor for increased cardiovascular morbidity and mortality. It has a complex pathogenesis, and traditional risk factors are not able to fully explain its high incidence and prevalence. Several substances have been identified, and they seem to play important roles in different physiological functions. This chapter will review traditional risk factors such as hypertension, diabetes, dyslipidemia, and left ventricular hypertrophy. The most relevant bibliography will be referred, and also interventional studies will be discussed. Other new emerging factors associated with the osteomineral metabolism have been described, mainly in advanced stages of CKD, and frequently are associated with higher cardiovascular risk, which in turn will contribute to the unfavorable prognosis of this population.


There are two issues of social importance in relation to nutrient cycling. The first is the depletion of nutrients in croplands and rangelands. The second is the overabundance of nutrients through the enhancement of inputs, particularly in freshwater bodies and coastal systems, which results in loss of biodiversity and ecosystem services through eutrophication. Nutrient cycling encompasses 15 or so elements, each with multiple chemical forms and phases, four media (air, soil, biomass and water) and many transformation and transport processes. It is not cost-effective to monitor them all, even in intensive research sites. The two key elements involved in both fertility loss and eutrophication are nitrogen and phosphorus; thus their changes in nutrient pools and fluxes need to be monitored. Key anthropogenic nitrogen contributions are through atmospheric deposition and liquid waste streams. A sensitive impact indicator is the nitrogen saturation index, which rises abruptly when the absorptive capacity of the landscape is exceeded. Key anthropogenic phosphorus inputs are agriculture and, in certain locations, mining and industry. Monitoring phosphorus fertilizer application rates and local-to-regional nutrient balances is useful because phosphorus is highly conserved in ecosystems. Measurement of nutrients associated with sediment fluxes in rivers is important for both nitrogen and phosphorus, as well as for carbon balance. To place current fluxes and perturbations in perspective, historical records have to be established. Additionally, tools such as isotopic tracers, which can be used unequivocally to differentiate between the natural and anthropogenic components of nutrient cycles, need to be explored.


Human being destined to install, so that human being each other interesting between type or is other of type, interest to others intertwin on the basis of taking a fancy to each other between oposite gender is so-called Interest between person. As does at child entering adolescent world of them start to interest with friend coeval or of him, adolescent even also start to have requirement there will be his of friend able to comprehend about x'self. Interest factors causing adolescent each other interesting, for example contiguity, equation and others. Adolescent term or adolescence come from Latin Ianguage is adolescence meaning is adolescent, in broader congeniality include;cover maturity bounce emotionally, social, and physical. Do not only is adolescent of adolescent habit even mute deaf people sometimes interest with oposite gender, congeniality of deaf people and is mute itself is someone which cannot hear and talk with goodness so that become resistance everyday activity competently or is fair. In this research of researcher use research qualitative. That research qualitative is research having the character of or owning characteristic, that its data is told in a state of appropriately or
as it is, without altered in number or symbols. So that researcher obtain;get with interview, documentation and observation. Result of from research of adolescent interest of deaf people and mute with oposite gender is they are early with each other making friends, and very often meet causing interest, because them have equation so that process easy and quicker interest to take a fancy to a. And they is couple prefer to with deaf people child and mute or a group of because of them feel balmyly, near by, and can be trusted. They limit scope life of his social adolescently ordinary because in communicating them very difficulty.


We explore the constraints on the history of reionization from Planck 2015 Cosmic Microwave Background (CMB) data and we derive the forecasts for future CMB observations. We consider a class of monotonic histories of reionization as parametrized by two additional extra parameters with respect to the average optical depth used in the instantaneous reionization modeling. We investigate the degeneracies between the history of reionization and selected extensions of the standard cosmological model. In particular, we consider the degeneracies with the total mass of the neutrino sector and we discuss the possible correlation between the dark matter annihilation and the duration of reionization in the CMB. We use an extension to poly-reion model that was proposed in [1]. We compare the constraints from Planck 2015 data with the predicted constraints from possible future CMB mission as LiteBIRD, and we also use the proposed CORE-like specifications as an example of what higher resolution can bring in addition. We find that the degeneracy between the averaged optical depth and the duration of reionization will be substantially removed by both concepts. Degeneracies between the reionization history and either the total neutrino mass and properties of dark matter annihilation will also be improved by future surveys. We find only marginal improvement in the constraints on reionization history for the higher resolution in the case of long duration of reionization.


This document was originally conceived as a description of the radium studies that took place at Argonne National Laboratory. It soon became evident, however, that to document the widespread use of radium, a brief review of the application of radium in medicine and in the US dial painting industry is required. Further, because the Argonne studies were not the only such efforts, brief overviews of the other radium programs are included. Even so, much material has been omitted. The extensive references included will allow the interested reader to find additional information. The effects of internally deposited radium in humans have been studied in this country for more than 75 years. Some 2,400 subjects have had their body contents of radium measured, and a majority of them have been followed for most of their adult lives, to understand and quantify the effects of radium. Many more individuals acquired radium internally but were never measured. Some of this group have been located and followed until death; in these cases the cause of death is known without a body content measurement. As a consequence of the efforts made to locate, measure, and follow exposed individuals, a great deal of information about the effects of radium is available. Nevertheless, great gaps remain in the knowledge of radium toxicity. The Argonne study is the largest every undertaken of the effects on humans of an internally deposited radioelement, in which the insult has been quantitated by actual measurements of the retained radioisotope. The study has now been terminated, even though more than 1,000 subjects with measured radium burdens are still alive. This document is written as a brief summary of current knowledge accumulated in this incomplete study.


The Adi Granth ('original book'), the primary scripture of the Sikhs, comprises approximately 3,000 hymns. Although the authorship of the hymns is well recorded, the history of the compilaiton of the Adi Granth - the creation of the Sikh 'canon' - is the subject of considerable speculation and debate. In this book, Gurinder Mann attempts to construct a comprehensive picture of the making of Sikh scripture, drawing on the recently discovered early manuscriots as well as the extensive secondary literature on the topic. His findings on some key issues differ from the traditional Sikh position and from the hypotheses of the other 20th-century scholars, as well as raising some entirely fresh questions. Mann's revised and expanded picture of the history of the text and institution of Sikh scripture will be of interest not only to scholars of Sikhism and Sikh religionists, but to scholars of comparative canon formation.


The development of higher education in the Western countries involves ideas of internationalisation, included in curricular objectives. Policy-makers stipulate internationalisation ideologies, from a politico-economic perspective, where ideas about flows of various cultural elements are incorporated in visionary idealistic terms. Nevertheless teachers and students and others concerned with higher education, experience the nature and meaning of "internationalising higher education" and "an internationalised teaching and learning" as vague, ambiguous and difficult to transfer into educational practice. This thesis investigates the phenomenon of internationalisation through an empirical approach, focusing on the experiences of teachers and students.

The aim was to describe teachers´ and students´ experiences of internationalisation related to their educational context, as well as their experiences of aspects of internationalisation in a wider sense. Precise predefinitions were avoided due to an explorative research approach. An empirical investigation comprising four studies was conducted, involving interviews with students (studies I and II) and teachers (study IV) and a survey study involving teachers (study III) all participating in the basic program in the Swedish nurse education within higher education. A phenomenographic approach was used in the data collections and analyses.

The main results of the empirical study show that students hold qualitatively different understandings of internationalisation, also, the ways they structure their thinking about the phenomenon varies (studies I and II). The results show, that teachers understanding of internationalising higher education and their approach to an internationalised teaching and learning did not represent a shared culture and there was no shared curriculum including a distinct understanding of internationalisation (studies III and IV). Some students and teachers related personal growth to the learning of intercultural content.

Internationalisation of higher education has primarily been related to a broader post-industrial worldwide policy development, and to processes of techno-structural political and economical worldwide forces, and forces of internationalisation ideologies in terms of intentions and objectives. The presence of a pedagogical and didactical perspective on the issue, "internationalisation of higher education", is clearly insufficient represented as a basis for understanding and concretising curricular objectives of internationalisation. Drawing from the thesis results, arguments are put forward emphasising a need to change/turn the focus towards how we deal with internationalisation of higher education. It is asserted that from a pedagogical and didactical stance there is a need for a development of a curriculum theory including internationalisation. The overall conclusion is that it will be a great challenge for policymakers as well as teachers, to address internationalisation of the Swedish nursing education within higher education from a pedagogical and didactical stance, when aiming at supporting students in their development of international competencies and capabilities.


Elections have emerged as a leading area for the application of biometric technology in developing countries, despite its high costs and uncertainty over its effectiveness. One-off voter registrations, as practiced in many countries and supported by donors, also often leave nothing behind in terms of permanent, sustainable, identification assets. Why then do donors support such programs? The paper considers the costs and benefits of technology, where the latter involves its potential to reduce the probability of seriously disputed elections that escalate into violence. Based on the limited data available, it finds that a reduction in the probability of post-election violence by only a few percentage points could offset the cost of the technology. However, this is possible only in particular situations where political parties value the legitimacy conferred by elections that are sufficiently credible to provide an acceptable basis for governing, but where democracy is not yet well-institutionalized. One priority is therefore to screen potential cases carefully. Another step towards using technology more effectively would be to build on the powerful momentum created by voter registration drives to strengthen permanent identity assets such as civil registration and national ID programs, so that they can provide a more sustainable foundation for subsequent voter rolls. This is possible with careful planning but may require some reconsideration of institutional mandates.


Abstract A professor's experience of attending the 17th annual Reconceptualizing Early Childhood Education (RECE) Conference on pedagogies of hope demonstrates her desire to experiment on an immanent plane. As she looks back on her past experiences of depression, working in a revolutionary psychiatric clinic, experiencing a near catatonic state, and an action research study of women in early childhood education at the precipice of an immanent plane, the reader is led on their own journey to consider deeply the differences between transcendence and immanence. In the end, the author's story of returning from a catatonic state through bodily movements and triumph in human relationships and connections demonstrates how one moves out of his or her own disconnection between mind and body. Further, the meaning in the experiences of the action research project - the phenomenon - occurs when a misrepresented group of early childhood workers discovers their own power and voice in overcoming transcended expertise. They rise in immanence like the Humpty Dumpties that needed to exchange and word their new agency, connecting in a worldwide rhizome (image of thought). Finally, the reconceptualists in early childhood education are asked to take in these experiences and play with them in order to resist transcendence and to determine their own outcome as an organization.


The nature of discrimination has been changing - over the past few decades – loosing its usual overt shapes (see Gaertner & Dovidio, 1986; McConahay, 1983; Swim, Aikin, Hall, & Hunter, 1995). According to Deitch et al. (2003), negative attitudes and discrimination are still persistent occurrences for members of stigmatized groups, even though they have turned into more subtle and interpersonal expressions (Frazer & Wiersma, 2001; Hebl, Foster, Mannix, & Dovidio, 2002; Hebl, King, Glick, Singletary, & Kazama, 2007; Heilman, Martell, & Simon, 1988). Thus, it is important to examine strategies that might reduce or avoid the display of such biases, because the effects of discrimination (e.g., formal, interpersonal) influence both persons who belong to stigmatized groups (e.g., lower self-esteem, avoidance of frustrating interactions, isolation, distress, depression) and non-stigmatized individuals (e.g., difficulties in interactions, frustration, tension).
The goal of the present research was to understand normal-hearing listeners' emotional responses to the speech of hearing impaired individuals, and examine the extent to which these stigmatized persons themselves are able to reduce negative emotions felt by able people while listening to them, by acknowledging their disability and showing an accepting, positive outlook with respect to their impairment and the personal and social difficulties that they have to face in they everyday life. Hearing impaired individuals, unlike individuals who are deaf, do receive limited auditory feedback. Because they are limited in their ability to hear—even when they use hearing aids or cochlear implants—they develop a unique style of oral communication, which is different from that of either normal-hearing or deaf individuals' (Gerard et al., 2010). The speech style of the hearing impaired may lead to problems in communication, such as non-normative style of speaking, difficulty in understanding other people and in being understood (Mackenzie & Smith, 2009). As a result, they face social and personal challenges that can affect their psychological well-being as well as social life, which are distinct from the challenges faced by deaf individuals. It is important to note that we do not believe that stigmatized persons should be only responsible for thwart the discrimination they experience in their everyday life; instead, social policies should also take such responsibility. As such, they may benefit interpersonally and socially from engaging in compensatory strategies (see Branscombe, Schmitt, & Harvey, 1999; Kessler, Mickelson, & Williams, 1999).
Our research represents an important contribution to the study of the intergroup bias which involves hearing impaired individuals as part of the normal-hearing community, that is a largely under researched field in Social Psychology. Moreover, it is the first time – to our knowledge – that a research focuses specifically on the study of the emotional reactions evoked by the speech of individuals with a partial hearing loss: this is a sensorial disability, which is deeply different – in terms of ability to hear, language development, communication difficulties, group identity, and social inclusion issues – from deafness. Finally, along with the clear importance of using specific compensatory strategies in order to reduce negative responses in normal hearing persons, findings of this study spread a light on the fact that more research is needed in this field. Thus, future investigations might inform interventions aimed to reduce tension and facilitate positive interactions between normal hearing persons and hearing impaired individuals, since an inclusive culture is more likely to develop when discrimination, in all of its forms, ceases to exist (Human Rights Campaign Foundation, 2004).


The Long History of field research at Grasshopper, a massive, 500-room pueblo in an isolated mountain meadow in east-central Arizona, has produced a wealth of architectural information. Drawing on this extensive research, Charles Riggs reconstructs the pueblo and provides a glimpse into the everyday life of the community at a critical time in Southwest prehistory.Between AD 1300 and 1330 a group consisting mainly of newcomers to the area established and then enlarged Grasshopper. From the architectural remnants excavated by the University of Arizona Archaeological Field School it is possible to determine that the earliest arrivals settled Grasshopper relatively quickly and that subsequent groups from the region and the Colorado Plateau built their houses next to kinsmen. The houses of locals and immigrants remained separate in discrete room blocks despite their occupants' participation in communal groups.Ultimately short-lived, by AD 1330 the influx of immigrants tapered off and the architecture came to reflect a more seasonal, less intensive use of the area. Eventually the community was abandoned and the walls were left to crumble. In The Architecture of Grasshopper Pueblo, Riggs gives us a new view of community life at this ancient Puebloan site.


In participants' narratives, observers' accounts, and scholarly analyses of U.S. counterhegemonic social movements, one frequently encounters the term 'faith' in characterizations of participants' engagement with a movement and its goals. In such references, people use the term 'faith' and related terms to signal that participants engage with the movement in a manner that is traditionally associated with religion and religious faith (even when a movement is overtly secular in orientation); that is, participants give themselves over to the cause with which they are involved. Using 'faith' as a starting point, I address the following questions: What is the nature of participants' engagement in a counterhegemonic social movement? How is that engagement perceived and confronted by outside observers? How do this engagement and perceptions of it influence the dynamics within counterhegemonic social movements? In order to answer these questions, I examine three U.S. social movements between 1890 and 1940. The first case surveys news coverage of the 1890 Lakota Ghost Dance, focusing on outsiders' perceptions of Ghost Dance faith, examining charges of delusion and fanaticism, and considering the ways in which these perceptions affected responses to the movement. The second case tracks messianism in three books by W. E. B. Du Bois in order to understand his attempts to theorize the nature and role of faith in the cause of racial liberation. The third case explores the dynamics of 1930s U.S. communism by investigating participants' own understandings of the category of 'faith,' as well as examining critics' and historians' analyses of the movement, given their own use of the term 'faith.' Based on these case studies, I argue that taking a collective counterhegemonic stand in order to achieve substantive social change often involves a quality of engagement that: opens one up to charges of delusion and fanaticism; requires conscious and self-critical cultivation on the part of participants and leaders; and treads a find line between prophetic vision and dogmatic blindness. Throughout this dissertation, I demonstrate the centrality of this kind of engagement---this phenomenon of 'giving oneself over to a cause'---in the dynamics of counterhegemonic social movements.


1. The green gland of Palaemonetes (and Palaemon) at the time of hatching of the larva has not developed a lumen, although the external opening can be detected. When the larva leaves the egg the lumen commences to open, and the gland consists of an end-sac and a U-shaped tube, of which the distal portion gives rise to the bladder. The bladder then enlarges greatly, growing at first inwards towards the middle ventral line, then upwards, within the oesophageal nerve-ring and anterior to the oesophagus, to the middle dorsal line, where it meets its fellow of the opposite side. The two bladders grow backwards over the stomach and beneath the dorsal sac, subsequently fusing together in the middle line to form the unpaired nephro-peritoneal sac. 2. The shell-glands are the functional excretory organs at the time of hatching and during the latter part of the embryonal period. They open at the bases of the second maxillae, and each consists of an end-sac and a Y-shaped renal tube, which have the typical structure of a crustacean nephridium. 3. A dorsal sac, which is completely enclosed by an epithelial lining, persists in adults of Palsem on, Palaemonetes, and Crangon. This sac, which does not contain blood, lies upon the nephro-peritoneal sac and the front end of the ovary, being much enlarged at its posterior end. The cephalic aorta (ophthalmic artery) lies within the dorsal sac. 4. At its anterior end the dorsal sac is surrounded by a mass of tissue which appears to be producing blood-corpuscles. 5. The dorsal sac is formed as a hollowing out in masses of mesoderm-cells, which lie on either side of the cephalic aorta. Two lateral cavities are thus formed, which increase in size and unite below the aorta. Taking into account this mode of development, a comparison with Peripatus shows that the dorsal sac is homologous with the dorsal portions of the mesoblastic somites of that animal, and must therefore be regarded as a true cœlom. 6. The body-cavity of these Crustaceans varies in different regions. ( a ) In the anterior part of the thorax it consists of a true cœlom (the dorsal sac and nephridia) and a haemocœle. The haemocœle consists of (1) a central cavity, in which the stomach and intestine, the liver and the nerve-cord lie; (2) two lateral cavities, which contain the end-sac and proximal end of the tube of the shell-gland, and which communicate with the central cavity and with the cavities of the legs; and (3) these leg-cavities, which, in the second maxillae, contain the tube of the shell-gland. (b) In the posterior part of the thorax the body-cavity is entirely a haemocœle. It consists of (1) the pericardial cavity, in which lies (2) the heart, and which is separated by the pericardial septum from (3) the central cavity of the body, which contains the genital organs, liver, intestine, and nerve-cord; (4) the lateral cavities, which communicate with the central cavity and with (5) the cavities of the legs. (c) In the abdomen the body-cavity is entirely a haemocœle. It consists of a dorsal and a ventral sinus, which communicate with one another by lateral sinuses.


There is increasing recognition of the role of local government in the protection and realisation of human rights obligations. Recent studies on links between local government, decentralisation and human rights are evidence of this growing recognition. In Africa, there are newly-formed pan-African institutions on local government. Local authorities and national local government associations have also formed a regional association. National ministries in charge of local government have formed a regional inter-ministerial forum on local government and decentralisation. This trend is replicated at sub-regional levels in Africa. While the place and role of local government in international human rights law are not yet fully understood, the formation of these institutions provides an appropriate avenue for the same. The article makes a case for institutional collaboration between these regional institutions, sub-regional institutions and the African Commission on Human and Peoples' Rights in order to achieve more effective rights protection. While this article presumes that such institutional collaboration will lead to better protection of human rights, it makes a further argument that this will only happen where the specific gaps identified are addressed to strengthen the role of local government in human rights.


This article considers the introduction of the partial defence to murder of loss of control in England and Wales. It examines whether the structuring of one of the triggers of the defence around the need for fear of serious violence will be helpful to jurors. The article looks at the case law of three jurisdictions: England and Wales, Germany and Australia. It considers a case from each jurisdiction which required the evaluation by the court as to whether someone who killed his or her abusive partner deserved to be excused criminal responsibility. The article considers how the fear of serious violence might be interpreted in the future by the English courts; and whether the jury will be able to appreciate the circumstances of an abused person when evaluating his or her actions. It will also consider how expert evidence may or may not help and what neuroscience tells us about the emotional states of anger and fear. Finally, it concludes by considering the question are these emotional states separable and, if they are not, will that pose a difficulty for jurors?


— This paper focuses on the new approach to develop an efficient Boost Converter by using coupled inductors. In order to eliminate voltage spikes, a buffer circuit is used in the converter. Coupling coils generate leakage flux, and energy in the leakage flux causes voltage spikes. With a high boost ratio, the active switches in the converter can maintain the proper duty cycle, which can significantly reduce voltage and current stress. Since the main switch and the auxiliary switch can be turned on by the zero voltage switching, the switching loss is reduced, and the conversion efficiency is significantly improved. In this paper, an experiment was conducted by building a 200W boost converter model. The results show that the conversion efficiency is greater than 90%, and the surge phenomenon can be effectively suppressed. Finally, the feasibility of low-voltage input systems was verified by photovoltaic and battery system.


BACKGROUND
The search of suitable indicators for estimating the risk of road traffic injuries is nowadays a relevant topic. The objective of this study was to carry out a comparative description of mortality and inhospital morbidity by age and sex, using population rates and mobility exposure related indicators.

METHODS
Cross sectional study in the Community of Madrid, 2003-2005. Population rates and mortality and morbidity rates per billion of persons-kilometers travelled and per million of persons-hours travelled were estimated and compared by age and sex. The Minimum Basic Hospital Discharge Data Set, the 2004 Mobility House Survey of the Community of Madrid and the mortality register of the Statistic Institute of the Community of Madrid were used as information sources.

RESULTS
7,413 hospital discharges and 1,046 deaths were identified. Morbidity and mortality population rates in men were 62.24 and 9.20 respectively, and in women 23.80 and 2.97 per 100,000 inhabitants, being the highest rates those for men aged 16-24 years (119.27 hospital discharges and 12.00 deaths per 100,000 inhabitants). Women of 65 years and older showed the highest mobility related rates: 649.78 hospital discharges and 96.72 deaths per 10(9) km, and 13.11 hospital discharges and 1.95 deaths per 10(6) travelled hours.

CONCLUSIONS
Morbidity and mortality were higher in men for the three indicators. Rates referred to mobility exposure, faced to population rates, decrease mortality and morbidity due to road traffic injuries in men and young ages and increase both in advanced ages.


Aerospace structures manufacturers find themselves frequently engaged in large-scale 3D metrology operations, conducting precision measurements over a volume expressed in meters or tens of meters. Such measurements are often done by metrologists or other measurement experts and may be done in a somewhat ad-hoc fashion, i.e., executed in the most appropriate method according to the lights of the individual conducting the measurement. This approach is certainly flexible but there are arguments for invoking a more rigorous process. Production processes, in particular, demand an automated process for all such "routine" measurements. Automated metrology offers a number of advantages including enabling data configuration management, de-skilling of operation, real time input data error checking, enforcement of standards, consistent process execution and automated data archiving. It also reduces training, setup time, data manipulation and analysis time and improves reporting. This paper draws on experiences from a recent automated metrology project and examines some of the challenges and benefits of successful measurement automation.


Masters thesis MA program in the History of the Decorative Arts and Design Cooper-Hewitt, National Design Museum, Smithsonian Institution and Parsons The New School for Design


PURPOSE
To compare caries experience and periodontal status between two U.S. populations that lived a century apart.

MATERIALS AND METHODS
The University of Pittsburgh, School of Dental Medicine possesses a collection of skulls that was organised in the first half of the 20th century. Those individuals are likely to have lived in the northeast United States during the late 19th century and the early 20th century. The present study measured caries and periodontal disease morbidity in the collection of skulls and compared the data with current prevalence rates of these diseases in the United States (from the third National Health and Nutrition Examination Survey 1988-94).

RESULTS
Periodontal health appears to have improved since this population resided, over 150 years ago. On the other hand, Americans between the ages of 16 and 39 appear to have the same prevalence of caries as a group of individuals that lived 150 years ago.

CONCLUSIONS
The periodontal health of Americans has probably improved in the last 100 years. The individuals identified that were free of caries and periodontal disease among the group that lived during the 19th century may have some protective factor against these diseases.


Productivity growth in virtually all west European countries exceeded that of the United States throughout the period 1950 to 1995. Since then American productivity performance has strengthened and that of the EU has weakened. The most important reason is contrasting experiences with Information and Communications Technology (ICT). The article argues that this may reflect a failure of European countries to update their 'social capability' to the requirements of a new technological epoch and points in particular to weaknesses in human capital formation and to excessive employment protection as obstacles to rapid realization of the productivity potential of ICT.


Speciation is the process in which reproductive barriers evolve between populations. In this thesis I examine how sexual signals contribute to the maintenance, reinforcement or breakdown of reproductive barriers.Male pied flycatchers (Ficedula hypoleuca) and collared flycatchers (F. albicollis) differ in song and plumage traits. However, where the two species coexist, several pied flycatchers sing a song resembling the collared flycatcher (mixed song). Mixed song is not caused by introgression from the collared flycatcher but is due to heterospecific copying. Mixed song provokes aggressive behaviour in collared flycatcher males and leads to heterospecific pairing and maladaptive hybridization. The species differences in song were found to be larger in an old than a young hybrid zone. This was due to a reduction in the frequency of mixed song in the pied flycatcher and a divergence in the song of the collared flycatcher. Apparently, mixed song causes maladaptive hybridization, which over time leads to reinforcement of reproductive barriers by a song divergence.Previous studies have shown that a character displacement in male plumage traits reinforces species barriers. Hence both plumage and song divergence reduce the incidence of hybridization. The evolution of male plumage traits has been so rapid, or selection has been so strong that rapidly evolving molecular markers are unable to trace it.Hybrid females mate with a male of the same species as their father. Previous studies have shown that females use male plumage traits controlled by genes linked to the sex chromosomes (the Z) in species recognition. An association between preference and a sex-linked trait through the paternal line may render reinforcement of reproductive barriers more likely.In conclusion, sexual signals are affected by species interactions that cause breakdown or reinforcement of reproductive barriers.


Epidemiology studies can be used to establish only general causation, but there are many criteria that can be employed to test those studies EPIDEMIOLOGY studies examine populations--generally smaller subsets or samples of populations--in an attempt to determine whether there is an association between exposure to a substance or factor and subsequent disease or injury. These studies are commonly used in the courts to support or refute claims that exposure to a substance or factor caused a disease or an injury in a specific plaintiff or group of plaintiffs. The problems are (1) on what issues are epidemiological studies properly used and admitted in evidence, and (2) how a particular study was carried out and effect that may have on its admissibility.(1) USE AND ADMISSION A. Relevance Epidemiology studies are relevant only to general causation. To satisfy the burden of proving causation, plaintiffs must show both (1) general causation--that is, whether the exposure or substance is capable of causing the alleged disease or injury, and (2) specific causation--that is, whether the exposure or substance actually caused the disease or injury in the specific case at issue.(2) Results from epidemiology studies are relevant only to the issue of general causation and cannot establish whether an exposure or factor caused disease or injury in a specific individual.(3) Unless general causation has been established evidence of specific causation in an individual plaintiff is not relevant and not admissible. B. Necessity Human epidemiology studies are a primary and generally accepted methodology to investigate the existence of a causal relationship between exposure to a factor and subsequent disease or injury. They have been held to be the most useful and conclusive type of evidence and that they must be taken into account.(4) Depending on philosophical views and the facts of particular cases, courts have made varied pronouncements regarding the necessity of epidemiology studies in causal analysis. Many courts have held that it is necessary to offer epidemiology evidence to prove causation.(5) Courts have held that epidemiological studies are necessary to prove causation, but only if there is no biological evidence of a causal mechanism for the disease. For instance, in Daubert v. Merrell Dow Pharmaceuticals Inc. at the district court level, the court stated: "Absent a scientific understanding of the cause of [the injury or disease], causation may be shown only through reliance upon epidemiological evidence."(6) Courts also have held that epidemiology studies are valuable but not dispositive of the causation issue. Epidemiology studies do not always prevail over non-epidemiological evidence.(7) In inexplicable rulings that seem to beg the question of the necessity of epidemiology studies, a few courts have stated that epidemiology evidence should be required only when they are available or if it is possible to gather the data.(8) The far better view, and that consistent with the Supreme Court's directions in Daubert, is that tort cases must be decided on the basis of the best available scientific evidence at the time of trial. Dispute resolution in the tort system cannot wait or be undermined by the creation of lower standards simply because epidemiology evidence is not currently available. As the Fifth Circuit said in Moore v. Ashland Chemical Co.: "In sum, the law cannot wait for future scientific investigation and research. We must resolve cases in our courts on the basis of scientific knowledge that is currently available."(9) To round out all permutations, some courts have flatly held that epidemiology evidence is not required to prove causation in an exposure case.(10) CONDUCT Epidemiology studies must be conducted properly and utilized in the legal context following the scientific method. This approach contemplates at least five steps in the reasoning process: * Formulation of the hypothesis or research question; * Preparation of a written protocol or study plan that provides, in advance of gathering any data, the methodology to be followed in the study; * Execution of the protocol, that is, gathering data from the population specified using the methodology prescribed in the research plan; * Analysis of the data using the statistical methodology prescribed in advance in the protocol; and * Drawing permissible conclusions, if any, from the study results, including determining whether the study results ought to be utilized at all in forming conclusions or generalizing findings to the population at large. …


Alkyl and tertiary amine functionalized α-methyl styrene (AMS) monomers have been synthesized via reactive coupling of 3-isopropenyl-α,α-dimethylbenzyl isocyanate (TMI) with primary amines. Primary amines utilized include hexylamine, octadecylamine and N,N-dimethylethylenediamine to synthesize monomers, 3-hexyl-1-[1-(m-isopropenylphenyl)-1-methylethyl]urea (AMSC6), 3-octadecyl-1-[1-(m-isopropenylphenyl)-1-methylethyl]urea (AMSC18) and 3-(2-(dimethylamino)ethyl)-1-[1-(m-isopropenylphenyl)-1-methylethyl]urea (AMSDMA), respectively. The structures of these functionalized AMS monomers have been confirmed by 1H-NMR, 13C-NMR and FT-IR. AMS, AMSC6 or AMSC18 was then successfully copolymerized with maleic anhydride (MalA) via free radical polymerization initiated by azobisisobutyronitrile to synthesize alternating copolymers. Free radical homopolymerizations of AMS, AMSC6, AMSC18 and MalA were performed to reveal no monomer conversion by gas chromatography and no formation of polymer chains by gel permeation chromatography (GPC). Alternating copolymers were characterized by GPC, 1H-NMR, FT-IR and MALDI-TOF MS. Finally, post-polymerization modification of P[(AMSC18)-a-(MalA)] by imidization of the MalA repeat unit with a primary amine was performed. This leads to the synthesis of alternating dual functionalized copolymers in an efficient and simple way.


With more than 5,000 works cited, Handbook of Avian Hybrids of the World is the greatest compendium of information ever published on hybridization in birds. Worldwide in scope, it provides information on all reported avian crosses, not only those occurring in captivity, but also in a natural setting (approximately 4,000 crosses are covered). This book is a basic reference, intended both for the serious birder and the professional biologist. McCarthy's work fills a need for reference material that takes into account the last half century of data. It will be of interest to workers in a wide variety of fields, ranging from animal behavior to genetics, ecology, zoology, and systematics. In fact, it will make fascinating reading for anyone interested in birds and the natural world.


We investigated the thermal stability and interdiffusion behavior of new amorphous ZrAl-based spin valves (SVs) and compared them with similarly structured Ta-based top (T) and bottom (B) SVs. The magneto-resistance (MR) ratios of ZrAl-based T-and B-SVs were enhanced from 8.49 to 9.14% and from 6.91 to 7.54%, respectively. The Ta-based SVs degraded relatively quickly at elevated temperatures because of interlayer diffusion. In contrast, the MR ratio of the ZrAl-based T-SV decreased by only 6.6% (9.14 /spl rarr/ 8.54%), while that of the B-SV increased by 2.3% (7.54 /spl rarr/ 7.71%), after annealing at 300/spl deg/C for 240 min. This result and the Auger electron spectroscopy (AES) depth profile clearly showed that ZrAl-based SVs have high interdiffusion resistance. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) analyses of the root-mean-square (rms) roughness indicated that the ZrAl layer (0.162 nm) has a smoother interface than the Ta layer (0.431 nm). The ZrAl-based SV has a fine, dense microstructure. It resists interdiffusion at elevated temperature and results in superior thermal stability over traditional Ta-based SVs.


We have undertaken a deep (σ∼ 1.1 mJy) 1.1-mm survey of the z= 0.54 cluster MS 0451.6−0305 using the AzTEC camera on the James Clerk Maxwell Telescope. We detect 36 sources with signal-to-noise ratio (S/N) ≥ 3.5 in the central 0.10 deg2 and present the AzTEC map, catalogue and number counts. We identify counterparts to 18 sources (50 per cent) using radio, mid-infrared, Spitzer InfraRed Array Camera (IRAC) and Submillimetre Array data. Optical, near- and mid-infrared spectral energy distributions are compiled for the 14 of these galaxies with detectable counterparts, which are expected to contain all likely cluster members. We then use photometric redshifts and colour selection to separate background galaxies from potential cluster members and test the reliability of this technique using archival observations of submillimetre galaxies. We find two potential MS 0451−03 members, which, if they are both cluster galaxies, have a total star formation rate (SFR) of ∼100 M⊙ yr−1– a significant fraction of the combined SFR of all the other galaxies in MS 0451−03. We also examine the stacked rest-frame mid-infrared, millimetre and radio emission of cluster members below our AzTEC detection limit, and find that the SFRs of mid-IR-selected galaxies in the cluster and redshift-matched field populations are comparable. In contrast, the average SFR of the morphologically classified late-type cluster population is nearly three times less than the corresponding redshift-matched field galaxies. This suggests that these galaxies may be in the process of being transformed on the red sequence by the cluster environment. Our survey demonstrates that although the environment of MS 0451−03 appears to suppress star formation in late-type galaxies, it can support active, dust-obscured mid-IR galaxies and potentially millimetre-detected LIRGs.


Basophilia is a frequently observed hematological abnormality in chronic myeloid leukemia (CML), but its pathophysiological roles are undefined. We previously demonstrated that an inflammatory chemokine, CCL3, preferentially acts on normal hematopoietic stem/progenitor cells and crucially contributes to the maintenance of leukemia initiating cells (LICs) in bone marrow (BM) during the initiation process of CML. However, the major cellular source of CCL3 in BM and the precise mechanism of CCL3-mediated maintenance of LICs remain to be investigated. To delineate the cellular process facilitating this CCL3-mediated crosstalk between normal and leukemic hematopoiesis, we precisely examined CCL3-expressing cells and their functions in both normal hematopoiesis and CML leukemogenesis. Herein, we demonstrate that basophils can constitutively express CCL3 to negatively regulate the normal hematopoietic process, especially hematopoietic reconstitution after BM transplantation. Moreover, CCL3-expressing basophil-like leukemia cells were found to accumulate in CML BM and supported the predominant expansion of LICs therein. These observations suggest that intra-BM basophil expansion can favor leukemia-tropic hematopoiesis in CML by providing CCL3, a potent inhibitor of normal hematopoiesis and that basophil-derived CCL3 may be a novel target molecule for the treatment of CML.


A combined linear-response-frozen electron-density model has been implemented in a molecular-dynamics scheme derived from an extended Lagrangian formalism. This approach is based on a partition of the electronic charge distribution into a frozen region described by Kim-Gordon theory [J. Chem. Phys. 56, 3122 (1972); J. Chem. Phys. 60, 1842 (1974)] and a response contribution determined by the instantaneous ionic configuration of the system. The method is free from empirical pair potentials and the parametrization protocol involves only calculations on properly chosen subsystems. We apply this method to a series of alkali halides in different physical phases and are able to reproduce experimental structural and thermodynamic properties with an accuracy comparable to Kohn-Sham density-functional calculations.


PURPOSE
A novel method for in vivo proton beam range verification is presented, using energy-resolvable proton-induced prompt gamma lines.

METHODS
Prompt gamma-rays emitted near the end-of-range of a clinical proton beam originate from transitions between the lower states of excited nuclear reaction products. We developed a prompt gamma-ray detection system with the aim of resolving the resulting discrete gamma lines. The ability to quantify the strength of these lines can provide valuable information for in vivo range verification: known cross sections may be used as prior knowledge, and uncertainties resulting from differences in tissue composition could be reduced. A LaBr3:Ce scintillation detector was used, which provides high energy resolution. The pulses from the photomultiplier tube were acquired with analog-to-digital converters at high sampling rates, synchronized to the cyclotron radiofrequency to separate the quasi-continuous neutron-induced background from the prompt gamma signals of interest.

RESULTS
Preliminary measurements were performed with a 150 MeV proton pencil-beam targeted on the center of a water phantom with a 15 cm diameter. A 1 cm lead slit collimator was used perpendicular to the beam direction, centered at the end-of-range. The acquired gamma spectra show the 6.13 MeV gamma line from oxygen-16, and its escape peak, can be clearly resolved with an energy resolution of ∼1% FWHM.

CONCLUSION
Our results show the feasibility of measuring discrete prompt gamma lines using a practical detection system. These gamma lines can be attributed to specific nuclear reactions with established properties, potentially enabling accurate proton range verification using a small number of measurement points. Experiments with different collimators and proton energies are currently being performed to determine an optimal configuration for range verification.


ABSTRACT For more than 40 years, health and physical education (HPE) academics in universities and teacher education colleges have drawn attention to issues of social justice specific to the context of PE and advocated for teachers in fields, gymnasiums and other physical activity spaces to do a better job of promoting more equitable outcomes for all students. Building on this advocacy, in the late 1990s, countries such as Sweden, Norway and New Zealand designed HPE curricula that address social justice. However, limited research has focused specifically on the enactment of social justice in HPE practice. Drawing on a larger international project involving Sweden, Norway and New Zealand the aim of this article is therefore to explore the constitution of social justice pedagogies across these three different HPE contexts and more specifically how HPE teaching practice may be understood from regulative, normative and cultural perspectives on social justice. The data reported on in this paper were generated from educational acts, curriculum documents, observations of HPE lessons in each of the three countries and follow-up teacher interviews. In order to analyse the data, we employed Scott's (2008. Institutions and organizations: Ideas and interests (3rd ed). Sage) institutional theory to further understand and discuss the enactment of social justice across the three different countries in HPE practice. In our representation and analysis of the findings we draw attention to how social justice pedagogies are informed differently by institutionalised governing systems and therefore they may be enacted differently by teachers in different societies. In particular, we highlight the influence of (i) regulative; (ii) normative; (iii) cultural-cognitive elements on practice. We conclude by pointing out the complex interplay between regulative, normative and cultural-cognitive elements that both enable and constrain HPE teachers' enactments of social justice in HPE practice.


PURPOSE/OBJECTIVES
To understand the process used by surrogate decision makers who have chosen to withhold and withdraw life-sustaining measures in intensive care units (ICUs).

DESIGN
Grounded theory.

SETTING
Multihospital system in central Texas.

SAMPLE
17 surrogates who decided to withhold and withdraw life-sustaining measures from patients with a variety of diagnoses, including cancer.

METHODS
Surrogates were identified by review of charts of patients in ICUs. Interviews were recorded on audiotape and analyzed using the process of constant comparison. Saturation of data occurred when no new themes emerged.

MAIN RESEARCH VARIABLE
The surrogate decision-making process.

FINDINGS
Domains and their respective themes included: (a) the personal domain: rallying family support, evaluating the patient's past and present condition, and viewing past and future quality of life; (b) the ICU environment domain: chasing doctors, developing relationships with the healthcare team, and confirming probable medical outcomes; and (c) the decision domain: arriving at a new belief, getting alone to make the decision, and communicating the decision.

CONCLUSIONS
Surrogates use a definite process to make decisions regarding withholding and withdrawing life-sustaining measures for patients in ICUs.

IMPLICATIONS FOR NURSING
The results reveal opportunities for healthcare providers to improve education and change practice when supporting surrogates. Additional opportunities exist for further research to expand nursing knowledge related to end-of-life issues.


Children's books can vary greatly in the type of and depth of interaction that is required from the reader. The types of interaction demanded by different types of books can be explored using contrasting paradigms. Previously Timpany & Vanderschantz (2012) proposed a categorisation of interactive children's books that used two continuums that took into consideration Physical Enhancement and Content Sequencing. This paper looks at those categorisations made by Timpany & Vanderschantz (2012) and considers how the multitude of formats addresses either the physical or intellectual aspects of children's reading and how this then may be used to engage the reader. To do this, a database of 132 books was audited to assess the interactivity of these books against those categorisation systems. The range of books surveyed is discussed in terms of what methods are used to create the interaction within each of the interactivity levels and across types of books. Findings from this audit demonstrate interesting interactions between age, physical enhancement versus content sequencing, and the relationship of these to mechanisms for interactivity such as paper engineering, illustration and story structure. The majority of the books in the sample have no interactive qualities on one of the two-categorisation scales. Physically enhanced books were marginally more highly represented on the scale at higher levels of interactivity. Counter intuitively, the physically interactive pop up books were seen to fall predominantly in lower categories (1 or 2) for physical enhancement, while books requiring image search, an intellectual activity, were also predominantly in the lower categories (1 or 2) for content sequencing.


Globally, life expectancy is increasing, as is the need for effective care responses to chronic health conditions, global emergencies and health disparities. Alongside this is a shortage of skilled caregivers. This four-country qualitative study investigates the views of 'care' and 'care careers' of Generation Z (the next generation to join the workforce). Four cross-cultural themes emerged: conceptualising care; objects and subjects of care; recognising the challenges of care; and appreciating care work. Discussed in relation to Tronto's analysis of care, these themes illuminate Generation Z's commitment to care and highlight the need for organisational and political action to attract young people to care careers.


WITH A FORWARD BY J. G. BALLARD In 1953, in the presence of an investigator, Aldous Huxley took four-tenths of a gramme of mescalin, sat down and waited to see what would happen. When he opened his eyes everything, from the flowers in a vase to the creases in his trousers, was transformed. Huxley described his experience with breathtaking immediacy in The Doors of Perception. In its sequel Heaven and Hell, he goes on to explore the history and nature of mysticism. Still bristling with a sense of excitement and discovery, these illuminating and influential writings remain the most fascinating account of the visionary experience ever written.


Towards understanding the dynamics and eddy evolving processes in the greater Agulhas Current system, a Hybrid Coordinate Ocean Model (HYCOM) system has been set up to simulation the ocean circulation around Southern Africa in a hindcast experiment. In a region characterised by a general paucity of hydrographic observations, model validation from satellite remote sensing data products play an important role. In particular, radar altimetry observations from satellites are of beneficial use in the Agulhas Current regime, since it is known to exhibit some of the strongest mesoscale variability in the global ocean. Model validation from available in-situ data is presented with the focus on evaluating and implementing satellite altimetry data products for the purpose of validating the model mesoscale variability. An initial comparison of along-track sea level anomaly data from the Jason-1 satellite to merged gridded multi−altimeter data for the Agulhas Current suggested no significant loss of information in the generation of the merged maps. Thus allowing the use of the gridded data product in further model evaluation. It was found that the altimeter data provides good temporal and spatial comparisons, and as a by-product to the validation process, a frequency and variability study of the Agulhas Current regime was undertaken. Additionally to confirming strong seasonal signals in the region, they revealed that mesoscale eddies in the Mozambique Channel frequently interact at the Agulhas Retroflection. These observations are quantified statistically with the application of a Fourier analysis, which additionally provided a further method of validating the model simulation. The model simulation was able to represent the general characteristics of the circulation in the Agulhas regime, and supports many of the findings in the altimetry variability study. However, with the development of a large anticyclonic circulation feature upstream of the Agulhas Plateau in the current proper, the model simulation deteriorates in the later years. Available hydrographic data suggests a salinity deficit in the model fields, resulting in reduced baroclinic gradients, which in addition to other numerical instabilities may provide an explanation for the development of this feature. With continuously improving numerical schemes, increased computing power, and improved data assimilation techniques these models become increasingly realistic. As an oceanographic tool, the development of numerical models is vital, the first steps towards setting up and validating a regional HYCOM model for the oceans around Southern Africa are presented.


This study focuses on characteristics, challenges, and benefits of practicing social work in the Upper Peninsula (UP) of Michigan. Using a mixed-methods design, data were analyzed to determine demographic descriptors, seek differences between groups, and learn why social workers pursue and remain in social service employment in the UP. In addition, challenges and benefits of rural practice and perceptions of living and working in this region are addressed. Quantitatively, differences were found between younger and older social workers regarding where they currently live and where they grew up, and whether or not they were raised in a rural location. Qualitative findings suggest that professional challenges to practice include responding to the effects of persistent poverty and unemployment, lack of specialty care for children and families, and inadequate transportation. Benefits of practice include quality community experiences, proximity to familial systems, and professional connectedness.


Cloud computing is an emerging technology which provides the computing and data storage services in the form of clusters. User can share data from one cluster to other or in same cluster. Data integrity is the major security issues in the shared cloud environment because after store/share data in cloud, user lose their control. This paper describes the data traceability methodology, when the user share data in a shared cloud from one location to another location. In this methodology user make a random challenge to third party like public verifier to check the metadata. This public verifier improves the data integrity of the cluster which contains the identification of the signer and information of metadata. This mechanism can be referred as Shared Data Traceability Protocol (SDTP) in cloud environment.


In order to realize a versatile high throughput production of micro-optical elements, UV-curable polymer composites containing titanium dioxide nanoparticles were prepared and characterized. The composites are based on an industrial prototype epoxy polymer. Titanium dioxide nanoparticles smaller than 10 nm were synthesized by the nonaqueous sol method and in situ sterically stabilized by three different organic surfactants. The composites exhibit high transparency. Distinct alteration of optical transmission properties for visible light and near IR wavelength range could be avoided by adaption of the stabilizing organic surfactant. Most importantly, the refractive index (RI) of the composites that depends on the fraction of incorporated inorganic nanoparticles could be directly tuned. E.g. the RI at a wavelength of 635 nm of a composite containing 23 wt% titanium dioxide nanoparticles is increased to 1.626, with respect to a value of 1.542 for the pure polymer. Furthermore, it could be demonstrated that the prepared inorganic–organic nanocomposites are well suited for the direct fabrication of low-cost micro-optical elements by nanoimprint lithography. A low response of the optical composite properties to temperature treatment up to 220 °C with a shrinkage of only about 4% ensures its application for integrated micro-optical elements in industrial production.


The Indian State of Kerala with a per capita income of around 1% of that of the wealthiest countries, has achieved good health comparable to theirs. For example the infant mortality rate for Kerala in 2000 was 14/1000 live births (1) compared with 7/1000 for the USA (2). Life expectancy at birth was 76 years for women and 70 for men in Kerala; in the United States these figures were 80 and 74 respectively (2). However, Kerala's per capita expenditure on health was only US$ 28 whereas that of the USA was USS 3925 (3). The most important reasons for this good health in Kerala are probably the following: its high level of female literacy (87%); access to health care (e.g. 97% institutional deliveries); a good public distribution system (PDS), which provides essential food items at subsidized rates (the system covers 96% of the population); political commitment (40% of the state budget went to the social sector till recently -- 15% to health, and 25% to education); good communication and transport (newspapers, telephones, rural roads); land reforms (land distributed to the poorest and the landless) which helped reducing inequality in land and income; and Christian missionaries who started schools and hospitals, mostly in rural areas (4). Overall, the achievements of Kerala seem to result from a relatively fair distribution of wealth and resources across nearly the entire population of the state (5). Globalization as promoted by the World Trade Organization (WTO), the World Bank, the International Monetary Fund and the transnational corporations has created a new world order. One of its major impacts is increasing inequality, which is detrimental to Kerala's health achievements. The Indian government initiated a major economic reform in June 1991 to increase economic growth. Social sector expenditure declined considerably during the first few years of this reform, resulting in stagnation in the development of public sector facilities. In spite of the high demand for health care, the Kerala government could not increase its hospital beds substantially, for lack of resources for the health sector. During the 10 years from 1986 to 1996, public sector hospital beds in Kerala increased by only 5.5%, from 36 000 to 38 000, while in the private sector there was a 40% increase, from 49 000 to 67 500. Furthermore, the quality of the public health sector decreased because the financial restrictions affected supplies, including drugs, more than the salaries of the well-organized and militant employees (6). Taking advantage of this situation, the unregulated private sector in Kerala opened many hospitals with high-tech equipment, thereby increasing the cost of health care. For example, in 1995, 22 out of the 26 computerized tomography scan centres in the state were in the private sector (6) and even the small remainder in the public sector is decreasing now. The introduction of user charges in the public hospitals as part of the reform process increased the out-of-pocket expenses of those using public health facilities. Household health expenditure in Kerala has increased over five times (517%) during a 10-year period of 1987-96. This increase was significantly higher (768%) among the poorest people than among the richest (254%). Even after adjusting for inflation the increase in health expenditure was about 4 times higher than the increase in consumer price index (7). The major reasons for this increase in health care costs are the increasing privatization of health care in the state, the increasing and often unnecessary use of technology, and a rise in drug prices. For example, Kerala has one of the highest rates of caesarean deliveries in the world now. Caesarean rates were reported to be 22% of all deliveries in rural areas and 34.5% in urban areas (8). The extra cost of caesarean deliveries in the state was estimated to be Rs 25 million (US$ 540 000) in the year 2000. Around 75% of the pregnant mothers had at least one ultrasonography test without any notable change in the management or outcome of pregnancy (9). …


For philosophers of science interested in elucidating the social character of science, an important question concerns the manner in which and degree to which the objectivity of scientific knowledge is socially constituted. We address this broad question by focusing specifically on philosophical theories of evidence. To get at the social character of evidence, we take an interdisciplinary approach informed by categories from argumentation studies. We then test these categories by exploring their applicability to a case study from high- energy physics. Our central claim is that normative philosophy of science must move beyond abstract theories of justification, confirmation, or evidence conceived impersonally and incorporate a theoretical perspective that includes dialogical elements, either as adjuncts to impersonal theories of evidence or as intrinsic to the cogency of scientific argumentation.


The Appalachian elktoe (Alasmidonta raveneliana) is endemic to the Blue Ridge Physiographical Province in western North Carolina and eastern Tennessee. Populations are small and geographically isolated in the headwaters of 10 streams in western North Carolina. Appalachian elktoe populations face a range of threats including climate and land use change, population fragmentation and modification of in-stream habitat. I examined long term (1970-2009) water chemistry and temperature data obtained for 19 streams that historically supported Appalachian elktoe populations. Streams were grouped into two categories: those with apparently stable populations and those with extirpated or severely declining populations. I found that streams with stable Appalachian elktoe populations were cooler with higher dissolved oxygen and lower specific conductance levels compared to streams with declining or extirpated populations. Next, in 2015, I surveyed Appalachian elktoe populations across the Nolichucky drainage at 25 sites and quantified in-stream habitat variables. I used USGS land use data for 1992 and 2011 for all sites. Land use in all streams was predominantly forest with some catchments having >90% forest in both 1992 and 2011. I found that streams with suitable Appalachian elktoe habitat have significantly more forest cover and less disturbance than streams with declining or extirpated populations.


We report on THz time-domain spectroscopy on multiferroic GeV4S8, which undergoes orbital ordering at a Jahn-Teller transition at 30.5 K and exhibits antiferromagnetic order below 14.6 K. The THz experiments are complemented by dielectric experiments at audio and radio frequencies. We identify a low-lying excitation close to 15 cm-1, which is only weakly temperature dependent and probably corresponds to a molecular excitation within the electronic level scheme of the V4 clusters. In addition, we detect complex temperature-dependent behavior of a low-lying phononic excitation, closely linked to the onset of orbitally-driven ferroelectricity. In the high-temperature cubic phase, which is paramagnetic and orbitally disordered, this excitation is of relaxational character, becomes an overdamped Lorentzian mode in the orbitally ordered phase below the Jahn-Teller transition, and finally appears as well-defined phonon excitation in the antiferromagnetic state. Abrupt changes in real and imaginary parts of the complex dielectric permittivity show that orbital ordering appears via a structural phase transition with strong first-order character and that the onset of antiferromagnetic order is accompanied by significant structural changes, which are of first-order character, too. Dielectric spectroscopy documents that, at low frequencies, significant dipolar relaxations are present in the orbitally ordered, paramagnetic phase only. In contrast to the closely related GaV4S8, this relaxation dynamics that most likely mirrors coupled orbital and polar fluctuations does not seem to be related to the dynamic processes detected in the THz regime.


Synthetic forsterite samples were shear-deformed at 11 GPa, 1400°C in the multianvil apparatus. The deformation microstructures have been characterised by SEM, EBSD, X-ray diffraction peak broadening and strain anisotropy analysis, and TEM. Different time durations have been characterised with a view to follow the evolution of strain and stress in high-pressure deformation experiments. A high density of [001] dislocations is introduced during pressurization at room temperature although no significant macroscopic shear or crystal preferred orientations are induced at this stage. The deviatoric stress is probably on the order of 1.5 GPa. Heating at 1400°C leads to a rapid decrease of the density of these dislocations. The shear deformation at high-temperature leads to measurable strain and development of crystal preferred orientations after one hour. Stress and strain-rate continue to decrease with time, such that eight hour experiments exhibit microstructures where recovery is apparent. At this stage, the stress level is estimated at ca. 100 MPa from dislocation density measurements. Crystal preferred orientations and TEM characterisation show that glide of [001] dislocations on (100) or (010) is the dominant deformation mechanism. Further investigation is needed to determine whether inhibition of [100] glide in these experiments is due to the role of water or whether a physical effect of pressure is also contributing.


SYNOPSISIn this paper the characteristics of the self light of the retina are reviewed and compared with those of the light formed by reflex stimulation of the fundamental color sensations. For this purpose the numerous references to self light in Peddie's recent work on Colour Vision are made the basis of study. Reasons are given to show that the reflex theory will satisfactorily account for the self light; its color tone; the possibility of an invariable color in the spectrum; the smaller degree of saturation of a color formed by mixture of two or more colors on the retina compared with that of its simple spectral equivalent; the threshold values of colors; and the effect on self light phenomena of changes in mechanical pressure in the retina due to variations in blood pressure.


Recently, three-dimensional (3D) object reconstruction using photon counting integral imaging (PCII) based on grayscale elemental images has been reported. In this paper, we present a multispectral PCII system using Bayer elemental images for multispectral visualization of photon limited 3D scenes. We measure the accuracy as well as the speed of demosaicing algorithms to estimate multispectral 3D scenes at low light levels. Experimental results demonstrate that the gradient corrected linear interpolation technique achieves better performance in terms of peak-to-SNR (PSNR) and faster computation.


Abstract Kamotoite-(Y) is a rare supergene product of uraninite hydration-oxidation weathering and its structure is unknown. Based on single-crystal X-ray diffraction data collected with high-redundancy using a microfocus source, kamotoite-(Y) is monoclinic, has space group P21/n, with a = 12.3525(5), b = 12.9432(5), c = 19.4409(7) Å, β = 99.857(3)°, V = 3069.8(2) Å3 and Z = 4. Crystals are pervasively twinned (two-fold rotation around [0.75 0 0.75]), giving a strongly pseudo-orthorhombic diffraction pattern. The pseudoorthorhombic pattern can be described with an orthorhombic super-cell (transformation matrix 0,1,0/1,0,1/ 3,0,1), approximately four times larger in volume then a true monoclinic unit cell. This unit-cell is the same as the cell given elsewhere for the structure of bijvoetite-(Y), another (REE)-containing uranyl carbonate. The successful structure solution and refinement (R = 0.044 for 6294 unique observed reflections), carried out using our choice of unit cell, as well as the superstructure refinement and comparison of the original structure data for bijvoetite-(Y) reveal that these two crystal structures are identical. The crystal structure of kamotoite-(Y) consists of electroneutral sheets of the bijvoetite-(Y) uranylanion topology and an interlayer with H2O molecules not-coordinated directly to any metal cation. Despite determination of the kamotoite- (Y) structure and demonstration that bijvoetite-(Y) has the same structure, the identity of these two minerals cannot be proved without additional study of the holotype material.


This paper investigates the history and concept of liberalism from its first uses to its most modern incarnations. The paper aims to serve as a primer for educators and educational researchers to better understand liberalism and its place as a foundational and controversial discourse in politics, social science, and education. Through reference to diverse sources, the essay inquires into the origins, nature, and usage of the term in multiple contexts. The paper concludes by speculating on the future use and applicability of this term. Liberalism has become a controversial term in large part because its meaning can vary so much depending on its use and context. Its most common usage at present is as a term of derision in American political debates. In the current politicai environment of the United States, conservatives often try to tarnish Democratic candidates by calling them "liberal." The implication is that "liberal" is a political epithet; it implies that the Democratic candidate has a "bleeding heart" and believes in the excesses of "60s era liberalism." The use of liberalism in this context (however deplorable) is not the primary concern of this essay. Further, dus essay is not particularly concerned with liberalism's former use in British politics per se, even though the present Conservative Party in the British government formerly went by the moniker of the "Liberal Party." The concern of this paper is to give the history of what is more accurately described as political liberalism. The context, in which I wish to proceed to describe liberalism, is in the field of political theory. The paper moves forward in the following sections: 1) basic definitions and underiying concepts of the term; 2) definitions from reference sources in political theory and political philosophy literature; 3) historical and recent works that address or critique the concept of liberalism; and 4) speculation on the future^of the idea of liberalism in the United States and the world. The OED: Where Else Could One Start in Defining Liberalism? The first task in better understanding liberalism is to define the word and then to look at its etymology. Obviously, the first place to look is die Oxford English Dictionary (OED). Unfortunately, the OED's definition of liberalism is not particularly enlightening. The OED states that liberalism is: "The holding of liberal opinions in politics or dieology; the political tenets characteristic of a Liberal" (OED, 1989a, para. 1). The first use of die term was in 1819; during this period, the term was most commonly employed in religious and political conflicts. Clearly, to better understand liberalism, one must take die next step and investigate, at least briefly, die definition of the term "liberal." In this case, the OED explodes with its usual assortment of definitions, etymologies, quotations, and timelines. The term, liberal, was first used around 1375, over 400 years before the term, liberalism, was first used in print In these early references, die meaning of liberal was associated with a certain societal position and its reflection in education. The OED defines it as: Originally, the distinctive epithet of those 'arts' or 'sciences' (see ART T) that were considered Nvorthy of a e opposed to servile or mechanical. In later use, of condition, pursuits, occupations: Pertaining to or suitable to persons of superior social station; 'becoming a gendeman' 0.). Now rare, exc. of education, culture, etc., with mixture of senses 3 and 4: Directed to general intellectual enlargement and refinement; not narrowly restricted to the requirements of technical or professional training. Freq. in uberai arts. (OED, 1989, para. 2) The earliest entries for this definition come to us in Old English, making their meaning more difficult to discern. One of the first clear uses of the word comes in die late 170Os from Burke and appropriately illustrates the hierarchal history of the term: "1757 BURKE Abridgm. …


Ground-penetrating radar (GPR) is being increasingly used over the last years in a wide range of applications, due to its flexibility and high potential to provide characterization and imaging of structures and materials. Overall, several reasons are contributing to increase the demand for the use of this tool and non-destructive testing techniques (NDTs) in general. Amongst all, it is worth citing technological advances of both hardware and software elements, an intrinsic lower significance of measurements provided by traditional monitoring techniques along with their greater invasiveness in measuring processes and, last but not least, the impacts of Global Economic Crisis on the use of economic resources affecting for years countries worldwide. The combination of such factors has led the interest of several skill profiles spanning from researchers, practitioners and end-users in general, and focused the attention of governments and local authorities on the high capabilities to gather a large amount of information in a relatively short time of surveying.
In the field of pavement engineering, GPR has been used since the early 1980s mostly focusing on the geometrical characterization of road structure, by evaluating layer thicknesses. Minor care has been given to the analysis of the main causes of damage and performance properties of pavements, in order to improve management of infrastructural asset through effective and efficient maintenance and rehabilitation actions, as well as to provide best conditions in design of new roads.
In that regard, this thesis is aimed to give a useful contribution also in the perspective of road safety issues by improving current processes of management and maintenance of road asset, along with the design of new roads, and provide effective support for the application and practical use of the tools described. Efforts have been spent in order to detect and quantify those physical and strength characteristics of road materials and subgrade soils that are relevant causes of damage, such that an effective planning of supporting actions for maintenance, rehabilitation and design of new roads may be timely performed.
Three main topics are addressed, namely: i) the evaluation of moisture spatial field in subgrade soils through a self-consistent frequency-based technique and the analysis of radar support scale in small-scale measurements of water content; ii) the potential to detect and quantify clay content in load-bearing layers and subgrade soils through different GPR tools and signal processing techniques, and iii) the possibility to infer strength and deformation characteristics of both bound, unbound pavement structures, and subgrade soils from their electric properties.
The results are encouraging for applications in the field of pavement engineering.


It remains a challenge to provide accurate and timely flood warnings in many parts of the western United States. As part of the Advanced Quantitative Precipitation Information (AQPI) project, this study explores the potential of using the AQPI gap-filling radar network for streamflow simulation of selected storm events in the San Francisco Bay Area under a WRF-Hydro modeling system. Two types of watersheds including natural and human-affected among the most flood-prone region of the Bay Area are investigated. Based on the high-resolution AQPI X-band radar rainfall estimates, three basic routing configurations, including Grid, Reach, and National Water Model (NWM), are used to quantify the impact of different model physics options on the simulated streamflow. It is found that the NWM performs better in terms of reproducing streamflow volumes and hydrograph shapes than the other routing configurations when reservoirs exist in the watershed. Additionally, the AQPI X-band radar rainfall estimates (without gauge correction) provide reasonable streamflow simulations, and they show better performance in reproducing the hydrograph peaks compared with the gauge-corrected rainfall estimates based on the operational S-band Next Generation Weather Radar network. Also, sensitivity test reveals that surficial conditions have a significant influence on the streamflow simulation during the storm: the discharge increases to a higher level as the infiltration factor (REFKDT) decreases, and its peak goes down and lags as surface roughness coefficient (Mann) increases. The time delay analysis of precipitation input on the streamflow at the two outfalls of the surveyed watersheds further demonstrates the link between AQPI gap-filling radar observations and streamflow changes in this urban region.


Approximate closed-form expressions are developed for predicting the effect of volume and interface absorption in thin films on the performance of quarter-wave multilayer coatings at normal incidence. For highly reflecting coatings the resulting expressions are an extension of Koppelmann's equation. The contribution of both dielectric and metal substrates is included explicitly in these equations as is the contribution of interface absorption and scattering losses. Closed-form expressions are also developed for the transmittance of absorbing and scattering antireflection coatings. Techniques for experimentally separating and determining interface and volume absorption in single-layer films and for estimating interfacial and volume scattering have recently been reported in the literature. The expressions developed in this paper make it possible using this experimental data to predict the performance of quarter-wave high-reflectance and antireflectance multilayer stacks at the design wavelength without recourse to a computer.


The Gakkel Ridge in the central Arctic Ocean was the object of an international expedition in the boreal summer 2001. This part of the mid-ocean ridge system is of particular geoscientific interest because of its extremely slow spreading rates and the variety of morphologic forms and features that are produced in this tectonic environment. Therefore, the multibeam bathymetric measurements were of special importance to the scientific goals of the exploration of this deep-sea ridge. The data was collected in the frame of a two-ship expedition by RV "Polarstern", equipped with the multibeam echosounder Hydrosweep DS-2, and by USCGC "Healy", which utilised a Seabeam-2112 multibeam system for the seafloor survey. This contribution deals with data editing and cleaning using CARIS HIPS. For the digital terrain modelling and mapping of the seafloor topography appropriate GIS tools (ArcInfo) were used. A comparison of the results from the two utilised multibeam systems will be presented. Finally products in form of bathymetric charts prepared with ArcMap in the western part of the Gakkel Ridge will be shown.


Since the onset of automation, industry has relied on adjustable speed drives to accurately control the speed of motors. Recent advances have increased the number of adjustable speed drives hitting the market. The proper operation of the speed drives requires electrical supply with relatively high power quality which is not the case in most industrial facilities. Power quality problems such as harmonic, sag, swell, flicker, and unbalance can trip the speed drive with a wrong message, which is referred as a premature tripping. Although the power quality problems can be mitigated by using custom power devices, they are bulky and costly. Moreover, they themselves might adversely affect the operation of the adjustable speed drive. A comprehensive study done in this thesis presents the overlooked effect of the custom power devices on the speed drive stability. It is found that the speed drive system might trip due to its interaction with custom power devices. Obviously, it is vital to increase ASD immunity to premature tripping because of poor power quality or custom power. This thesis offers fast, efficient and robust algorithms to achieve this immunity by retrofitting the ASD control unit and integrating the power conditioning function with the adjustable speed drive. Therefore, the power quality problem is mitigated and the drive system performance is significantly enhanced. Such integration requires the modification of the control unit by considering various elements such as envelope tracking, phase-locked loop, symmetrical component extraction, and the controller. Simple but robust and fast algorithms are proposed for such elements based on a newly developed energy operator algorithm. The developed energy operator and the developed algorithms overcome the drawbacks of the existing algorithms.


It has long been acknowledged within the scientific community that in the mid-term future the Earth will undergo important changes beyond those deduced from the past behaviour of known physical phenomena. For example, climate change due to rising temperatures is expected to influence several systems, like ocean levels, wind current and rain regimes. Global travel, urbanisation, biomedical manipulation and intensive agriculture are additional factors affecting natural systems which together in turn influence the diversity of plant, animals, and microorganisms in general. As a result, zoonoses represent 60,3% of emerging infectious diseases, more than 70% of which are caused by pathogens of wildlife origin (Jones et al. 2008). Whatever the action suffered by these subsystems (increase or reduction in species number), the fact is that currently we are unable to predict the exact outcomes of these changes.

This limitation to forecast the future does not prevent us to sketch scenarios for probable events, such as the emergence of unknown and lethal infectious agents. Advances in research of infectious disease and epidemiology have empowered society to respond quickly to this kind of threat, though not so effective as to the point of controlling or completely eliminating a disease. The Ebola epidemics is an example of such an event and its response.

Now we have another threat: the Zika virus (ZIKV) and its vector, the mosquito Aedes aegypti. The Director-General of the World Health Organization, on 1 February 2016, declared this to be a Public Health Emergency of International Concern (PHEIC). We can only speculate that the spread of both this virus and vector might be seen as signs of the changes anticipated by climatologists and ecologists. However, one thing is beyond any question or doubt: we have to start new ways to accelerate scientific collaboration, including access to data and exchange of research findings.

Recently, the Forum of Scientific Editors of FIOCRUZ decided collectively to give priority to the publication of papers regarding the Zika epidemic in their journals. In the context of this decision and the declaration of the Director-General of the World Health Organization, we, as the editors of the Memorias do Instituto Oswaldo Cruz (MIOC), have decided to create a section on the MIOC website called "Zika Fast Track", where research manuscripts relevant to the Zika epidemic will be posted. We have also decided to follow the example of the Bulletin of WHO (Dye et al. 2016) and make the data in these papers freely available for unrestricted use, distribution and reproduction provided that the original work is properly cited as indicated by the Creative Commons Attribution license (CC BY).

All research manuscripts concerning the Zika epidemic, after submission to the Memorias do Instituto Oswaldo Cruz, will be evaluated by an Editor and those considered relevant will be assigned a digital object identifier and posted online in the "Zika Fast Track" section of the Web-site within 24 hours. At the same time, manuscripts will be evaluated by peer review. Data in these manuscripts will thus be attributed to the authors while being freely available for reader scrutiny and unrestricted use, distribution and reproduction provided that the original work is properly cited as indicated by the Creative Commons Attribution license (CC BY 3.0). In papers accepted by the MIOC following peer review, this period of open data within the Zika Fast Track will be mentioned in the final publication. In case of rejection after peer review, authors are free to seek publication elsewhere.

Manuscripts can be submitted via the MIOC website memorias.ioc.fiocruz.br.


Recent decades have seen a focus on quality in healthcare. Quality has been viewed across 6 dimensions—safe, effective, patient‐centred, timely, efficient and equitable. As IT has enabled the transformation of other industries, there has been an increasing interest in the potential for learning health systems (LHS) to improve quality in healthcare. We are not aware of any systematic attempt to investigate the potential impacts of different types of LHS on quality within healthcare providers.


Last year at OOPSLA we presented a methodology, vertical profiling, for understanding the performance of object-oriented programs. The key insight behind this methodology is that modern programs run on top of many layers (virtual machine, middleware, etc) and thus we need to collect and combine information from all layers in order to understand system performance. Although our methodology was able to explain previously unexplained performance phenomena, it was extremely labor intensive. In this paper we describe and evaluate techniques for automating two significant activities of vertical profiling: trace alignment and correlation. Trace alignment aligns traces obtained from separate runs so that one can reason across the traces. We are not aware of any prior approach that effectively and automatically aligns traces. Correlation sifts through hundreds of metrics to find ones that have a bearing on a performance anomaly of interest. In prior work we found that statistical correlation was only sometimes effective. We have identified highly-effective approaches for both activities.For aligning traces we explore dynamic time warping, and for correlation we explore eight correlators based on statistical correlation, distance measures, and piecewise linear segmentation. Although we explore these activities in the context of vertical profiling, both activities are widely applicable in the performance analysis area.


Abstract. Despite a multitude of studies, overall erosion rates as well as the contribution of different erosion processes on Chinese Loess Plateau (CLP) remain uncertain, which hampers a correct assessment of the impact of soil erosion on carbon and nutrient cycling as well as on crop productivity. In this paper we used a novel approach, based on field evidence, to reassess erosion rates on the CLP before and after conservation measures were implemented (1950 vs. 2005). We found that current average topsoil erosion rates are 3 to 9 times lower than earlier estimates suggested. Under 2005 conditions, more sediment was produced by non-topsoil erosion (gully erosion (0.23 ± 0.28 Gt yr−1) and landsliding (0.28 ± 0.23 Gt yr−1) combined) than by topsoil erosion (ca. 0.30 ± 0.08 Gt yr−1). Overall, these erosion processes mobilized ca. 4.77 ± 1.96 Tg yr−1 of soil organic carbon (SOC): the latter number sets the maximum magnitude of the erosion-induced carbon sink, which is ca. 4 times lower than one other recent estimate suggests. The programs implemented from the 1950s onwards reduced topsoil erosion from 0.51 ± 0.13 to 0.30 ± 0.08 Gt yr−1 while SOC mobilization was reduced from 7.63 ± 3.52 to 4.77 ± 1.96 Tg C yr−1. Conservation efforts and reservoir construction have disrupted the equilibrium that previously existed between sediment and SOC mobilization on the one hand and sediment and SOC export to the Bohai sea on the other hand: nowadays, most eroded sediments and carbon are stored on land. Despite the fact that average topsoil losses on the CLP are still relatively high, a major increase in agricultural productivity has occurred since 1980. Fertilizer application rates nowadays more than compensate for the nutrient losses by (topsoil) erosion: this was likely not the case before the dramatic rise of fertilizer use that started around 1980. Hence, erosion is currently not a direct threat to agricultural productivity on the CLP but the long-term effects of erosion on soil quality remain important.


The article is in the context of linguistic and semiotic studies related to theoretical issues of base units' typology, in particular, theoretical linguistics and "pure" semiotics. Sign is one of the basic units of linguistics and semiotics. The way of understanding the nature and structure of the sign essentially influences the nature of almost all studies. The depth, consistency and completeness of perception of signs are reflected in the currently existing classifications of signs. The article fills in a gap in the perception of the sign variety nature in the semiotic and linguistic understanding. It provides a tool for the correct interpretation of a large body of facts related to the secondary use of proper names in the specific function and precedential units in a broad context. The analysis of the actual texts indicates that the current classifications of signs do not reflect in their entirety all the signs which actually exist and function in the space of language and culture. Beyond the limits proposed by these classification schemes are left the phenomena of sufficient frequency. The article based on the appositive and distribution methods describes and analyzes the type of signs that has not been previously perceived by researchers as an independent one and has not been studied at all. This sign is called a bifocal sign and it is consistently described in terms of its specific features which do not allow mixing it with other types of signs. The results show that an adequate interpretation of any text which includes a bifocal sign is impossible without taking into account the specificity of this sign.