The extent to which kinetic barriers to nucleation and growth delay the onset of prograde metamorphic reaction, commonly known as overstepping, is related to the macroscopic driving force for reaction, termed reaction affinity. Reaction affinity is defined in the context of overstepping as the Gibbs free‐energy difference between the thermodynamically stable, but not‐yet‐crystallized, products and the metastable reactants. Mineral reactions which release large quantities of H2O, such as chlorite‐consuming reactions, have a higher entropy/volume change, and therefore a higher reaction affinity per unit of temperature/pressure overstep, than those which release little or no H2O. The former are expected to be overstepped in temperature or pressure less than the latter. Different methods of calculating reaction affinity are discussed. Reaction affinity 'maps' are calculated that graphically portray variations in reaction affinity on equilibrium phase diagrams, allowing predictions to be made about expected degrees of overstepping. Petrological consequences of variations in reaction affinity include: (i) metamorphic reaction intervals may be discrete rather than continuous, especially in broad multivariant domains across which reaction affinity builds slowly; (ii) reaction intervals may not correspond in a simple way to reaction boundaries and domains in an equilibrium phase diagram, and may involve metastable reactions; (iii) overstepping can lead to a 'cascade effect', in which several stable and metastable reactions involving the same reactant phases proceed simultaneously; (iv) fluid generation, and possibly fluid presence in general, may be episodic rather than continuous, corresponding to discrete intervals of reaction; (v) overstepping related to slowly building reaction affinity in multivariant reaction intervals may account for the commonly abrupt development in the field of certain index mineral isograds; and (vi) P–T estimation based on combined use of phase diagram sections and mineral modes/compositions on the one hand, and classical thermobarometry methods on the other, may not agree even if the same thermodynamic data are used. Natural examples of the above, both contact and regional, are provided. The success of the metamorphic facies principle suggests that these kinetic effects are second‐order features that operate within a broadly equilibrium approach to metamorphism. However, it may be that the close approach to equilibrium occurs primarily at the boundaries between the metamorphic facies, corresponding to discrete intervals of high entropy, dehydration reaction involving consumption of hydrous phases like chlorite (greenschist–amphibolite facies boundary) and mica (amphibolite–granulite facies boundary), and less so within the facies themselves. The results of this study suggest that it is important to consider the possibility of reactions removed from equilibrium when inferring the P–T–t evolution of metamorphic rocks.


A finite element heterogeneous multiscale method is proposed for the wave equation with highly oscillatory coefficients. It is based on a finite element discretization of an effective wave equation at the macro scale, whose a priori unknown effective coefficients are computed on sampling domains at the micro scale within each macro finite element. Hence the computational work involved is independent of the highly heterogeneous nature of the medium at the smallest scale. Optimal error estimates in the energy norm and the L2 norm and convergence to the homogenized solution are proved, when both the macro and the micro scales are refined simultaneously. Numerical experiments corroborate the theoretical convergence rates and illustrate the behavior of the numerical method for periodic and heterogeneous media.


This research proposes a novel wireless information-centric networking (ICN) architecture, namely, Context-Aware Green ICN Model (CAGIM), which can adapt the power consumption of network nodes to optimized values according to the associated link utilization. The power adaption in ICN nodes is conducted through dynamically adjusting the link-rate corresponding to content popularity and traffic load to reduce wasteful energy consumption. Moreover, we propose a smart popularity-based caching strategy, called distinguished caching scheme (DCS), with the introduction of hot and cold-caching partitions of ICN node's cache storage for popular and non-popular content objects, respectively. DCS improves the content diversity of the cache storage by adjusting, for each content, the number of chunks to be cached at ICN nodes based on its type and popularity level. DCS thus can further decrease the network system power consumption, thanks to its improved cache hit that reduces network traffic load. Toward the goal of realizing a context-aware green wireless network system with efficient content delivery, we also design a Wi-Fi Direct based scheme as an alternative approach to minimize power consumption and latency by sharing essential/important content objects via direct communications with power-saving mechanisms in the case that wireless local area network connections are not available. The evaluation results show that CAGIM can improve network efficiency by reducing both hop-count and power consumption considerably compared with existing wireless network systems with different well-known caching schemes. This proposal enables a flexible and efficient content delivery mechanism for future networks with various real-life scenarios, like Green building, Green company, and Green campus content accesses.


A major difficulty construction companies are currently facing is the lack of interoperability of software applications to manage and progress in their business. Organizations are being pressured up by new business relationships, driven for instance by new contractual challenges, which the exchange of information and documents with new partners are often incapable of being executed automatically and in electronic format. This is principally due to problems of incompatibility with the information representation adopted by the software applications they are working with. This problem arises not only during the project phase but also across the whole life cycle that includes operation and maintenance stages. In order to create the enabling conditions for the deployment of the electronic collaborative and commerce platforms it is fundamental to understand the variables that may influence its development, and how they determine the configuration of the e-platform. This paper, after present technology driven standards for the construction industry data management, it proposes the adoption of the emerging Service Oriented and Model Driven Architectures to shift forward the interoperability paradigm in this industrial sector. The paper illustrates some scenarios where significant impact is expected when adopting the proposed methodology.


This paper looks at innovative strategies for how to effectively teach Public Diplomacy by integrating technology into the classroom. The results are based on a Foundations of Public Diplomacy class taught at American University in Spring 2012. The course explored recent shifts in public diplomacy toward virtual statecraft. As part of this focus, the syllabus integrated an ongoing social media dimension over the duration of the course. From the beginning, the course had a dedicated Twitter hashtag (#kelleypd) that gained traction and became part of the larger dialogue around the topic of public diplomacy. The second half of the class featured student presentations, which were required to include technology components. The results from the class showed a high level of participation and interaction within the class and into the larger community. In addition, the students gained skills in media creation that helped them to understand which tools would be appropriate in diverse situations.


Purpose – Social loafing is described in the literature as a frequent problem reducing individuals' performance when working in groups. This paper aims to utilize the social identity approach and proposes that under conditions of heightened group salience social loafing can be reduced and turned into social laboring (i.e. increased performance). Design/methodology/approach – Two experimental studies are conducted to examine the impact of participant's group membership salience on task performance. In Study 1, school teachers work either in coactive or in collective working conditions on brainstorming tasks. In Study 2, participants perform both a brainstorming task and a motor task. Findings – The results show social laboring effects. As predicted, participants in the high salient group conditions outperform participants in the low salient group conditions and the coactive individual condition. Practical implications – The results indicate that rather than individuating group members or tasks to overcome social loafing, managers can increase group performance by focusing on group members' perceptions of their groups as important and salient. Originality/value – The studies presented in this paper show that social identity theory and self categorization theory can fruitfully be applied to the field of group performance. The message of these studies for applied settings is that collective work in groups must not necessarily negatively impact performance, i.e. social loafing. By heightening the salience of group memberships groups can even outperform coactively working individuals.


OBJECTIVE
For many years, the treatment of X-linked childhood cerebral adrenoleukodystrophy (XALD) consisted of hydrocortisone replacement and a mixture of short chain-fatty acids, known as 'Lorenzo's oil'. Recently, bone marrow transplantation (BMT) has also been used.

CASE REPORT
We report the case of a patient affected by XALD who developed Graves' hyperthyroidism (GH) and Graves' orbitopathy (GO) after BMT and who we could follow-up for 6.5 years afterwards.

EVIDENCE SYNTHESIS
A boy affected by XALD was treated at the age of 6 years, with a whole BMT from his sister. One year after BMT, the transplanted patient presented TSH at the lower normal value and 3 years later he developed thyrotoxicosis. After a further 2 years, the patient developed GO, which showed clinical evidence of reactivation 5 years after its onset as a consequence of an attempt to treat thyrotoxicosis by means of I(131) (300 MBq). Seven years after BMT, the donor showed alterations of thyroid autoimmunity and 1 year thereafter she developed GH. She never presented GO during a subsequent 5 year follow-up.

CONCLUSIONS
This case illustrates that autoimmunity originating from a pre-symptomatic donor can be transferred into the host during allogeneic stem cell transplantation. In cases where autoimmune phenomena are recognized in the donor prior to donation, alternative donors or T-cell manipulation of the graft might be considered.


A dataset of 1408 comedians was created by scraping the English Wikipedia. Each comedian's sex was estimated based on gendered English pronouns and gendered categories. Overall, the distribution was 79% male. When examined over time, it was evident that the distribution was changing to become less male dominated. Among those born 1880-1910, 90% were male compared to 61% among those born 1980-1990. 17% of comedians were Jewish, nearly evenly distributed by sex. Comedians born around 1915 were found to live 5.4-10.4 years longer than matched members of the general population. Comedians were found to be highly educated, especially women. Comedians who were members of Scandinavian comedian clubs (n=235) were examined as an independent replication. Of these, 83% were male.


As a result of the NREN NIS award by National Science Foundation, non-
DDN registration services will soon be transferred from the DDN NIC to
the new Internet Registration Service, which is a part of an entity
referred to as the InterNIC. This memo provides information for the
Internet community. It does not specify an Internet standard.


BACKGROUND
The American College of Cardiology/American Heart Association exercise testing guidelines suggest that routine functional testing may benefit patients at high risk of restenosis, such as those undergoing multi-lesion percutaneous coronary intervention (PCI).

OBJECTIVES
To compare the six-month post-PCI clinical and procedural outcomes in patients following single- and multi-lesion PCI, and to examine the use of routine functional testing (ie, in all patients) versus selective functional testing (ie, only in those with recurrent symptoms) following multi-lesion PCI.

METHODS
Six-month outcomes among 562 patients after single-lesion PCI and 229 patients after multi-lesion PCI were examined. All patients were enrolled in the Routine versus Selective Exercise Treadmill Testing after Angioplasty (ROSETTA) registry, a prospective, multicentre registry examining the use of functional testing after successful PCI.

RESULTS
For single- versus multi-lesion PCI patients, respectively, rates of death (1.8% versus 2.2%, P=0.7) and myocardial infarction (0.7% versus 2.6%, P=0.03) were low in both groups. Rates of unstable angina (12.0% versus 11.7%, P=0.9) and the composite clinical end point of death, myocardial infarction or unstable angina (13.5% versus 13.9%, P=0.9) were similar. Multi-lesion PCI patients had a higher number of repeat PCI procedures (6.6% versus 13.4%, P=0.02) but there was no difference in the rates of coronary artery bypass graft surgery (3.0% versus 2.6%, P=0.7). A routine functional testing strategy was used in 28.0% of single-lesion and 31.6% of multi-lesion patients. In a multivariate analysis of the multi-lesion patients, routine functional testing was not associated with a significant reduction in the composite clinical event rate (odds ratio 0.5, 95% CI 0.2 to 1.7, P=0.27).

CONCLUSIONS
During the six-month period following successful PCI, clinical event rates were similar among patients undergoing single- or multi-lesion PCI. Routine functional testing was not associated with a statistically significant benefit in patients after multi-lesion PCI. However, additional study is required to better define the role of routine functional testing in this subgroup of patients.


This is the introductory chapter of Parchment, Paper, Pixels: Law and the Technologies of Communication. It discusses the impact that technological revolutions (in particular, writing, printing, and the Internet) have had on civilization in general and our legal system in particular. Wills, for instance, are quintessentially written text. The legal profession has developed distinct literary conventions regarding the drafting and interpretation of wills, often to the befuddlement of individual testators. If the textual practices of willmaking are often too strict, those relating to contracts may sometimes be too lax. Electronic contracting has taken off with vengeance and, while convenient, can sometimes make it too easy to "agree" to terms hidden under a computer icon. Statutes, like wills, are highly textual. The rule of law has been promoted by having them written down or, in modern times, being made widely available in printed form or on the Internet. Yet what they gained in stability they have lost in flexibility. Finally, judicial opinions or judgments, which were once considered a type of unwritten law, are rapidly becoming textualized, especially in the United States, but also to a lesser extent in England. As a result, legal reasoning may eventually be supplanted by close reading of the text, a trend likely to be exacerbated by accessing opinions online. It therefore matters - sometimes a great deal - whether a law or legal transaction is chiseled into stone, written on parchment, printed on paper, or embedded in pixels on a computer screen.


The solution of cooperative localization is of particular importance to teams of aerial or underwater robots operating in areas devoid of landmarks. The problem becomes harder if the localization system must be low-cost and lightweight enough that only consumer-grade cameras can be used. This paper presents an analytical solution to the six degrees of freedom cooperative localization problem using bearing only measurements. Given two mutually observing robots, each one equipped with a camera and two markers, and given that they each take a picture at the same moment, we can recover the coordinate transformation that expresses the pose of one robot in the frame of reference of the other. The novelty of our approach is the use of two pairs of bearing measurements for the pose estimation instead of using both bearing and range measurements. The accuracy of the results is verified in extensive simulations and in experiments with real hardware. At 6.5 m distance, position was estimated with a mean error between 0.021 m and 0.025 m and orientation was recovered with a mean error between 0.019 rad and 0.037 rad. This makes our solution particularly well suited for deployment on fleets of inexpensive robots moving in 6 DoF such as blimps.


New and innovative production equipment can be developed by introducing lightweight materials in modern day automotive industry production lines. The properties of these new materials are expected to result in improved ergonomics, energy savings, increased flexibility and more robust equipment, which in the end will result in enhanced productivity. Carbon composite materials are one such alternative that has excellent material properties. These properties are well documented, and the market for carbon composite materials is growing in many areas such as commercial aircrafts, sporting goods and wind turbines. However, when studying the use of carbon composite materials for production equipment in the automotive industry, it was found that there were few, if any, such examples.This paper focuses on innovative ways of making carbon composite materials available for designing automotive industry production equipment by introducing a design and material concept that combines flexibility, relatively low costs and high functionality. By reducing the weight by 60%, it was obvious that the operators were very positive to the new design. But just as important as the improvement of the ergonomic feature, the combination of low weight and material properties resulted in a more robust design and a more stable process of operation. The two main designs (two versions of the steel-based design were constructed) were developed sequentially, making it difficult to compare development costs since knowledge migrated from one project to the next. In this study, the gripper was manufactured in both carbon composite material and steel. The different designs were compared with reference to design costs, functionality, robustness, product costs and ergonomics. The study clearly shows that the composite material represents a favorable alternative to conventional materials, as the system combines superior properties without significantly increasing the cost of the equipment. This paper describes the approach in detail.Copyright © 2013 by ASME


The European Union (EU) aims to develop "special relations" with the eastern and southern neighbourhood of the enlarged EU. What exactly these privileged and special relations entail is still not clear, and the tailored Action Plans do little to clarify this point. Almost fourteen years after launching the European Neighbourhood Policy (ENP), it is time to take stock of the relations between the EU and its target countries. "One size fits all" is old news. Focusing on the eastern dimension of the ENP, this paper examines Germany's internal media perception of individual EU relations with the "near" neighbours of the Eastern Partnership (EaP). The key questions of this paper are the following: How are the relations between the EU and the eastern EaP countries, Belarus, the Republic of Moldova and Ukraine, framed and communicated by leading German press outlets and what do these frames and images mean for the EU's outlook towards the eastern neighbours? Katharina Kleinschnitger


Dominating broadcasting is a domination-type structure that models a transmission antenna network. In this paper, we study a limited version of this structure, that was proposed as a common framework for both broadcast and classical domination. In this limited version, the broadcast function is upper bounded by an integer $k$ and the minimum cost of such function is the dominating $k$-broadcast number. Our main result is a unified upper bound on this parameter for any value of $k$ in general graphs, in terms of both $k$ and the order of the graph. We also study the computational complexity of the associated decision problem.


Two stacked parasequences exposed continuously along a 35-km dip section in the Permian lower Waterford Formation, Karoo Basin, South Africa, form basin margin–scale clinothems, and their internal facies distributions have been mapped out from shelf to upper submarine-slope settings. Sedimentary facies changes have been determined by walking out key surfaces between measured sections. The two parasequences (Waterford clinothems WfC 3 and WfC 4) share progradational profiles, but WfC 3 is characterized by a strong fluvial influence, whereas overlying WfC 4 is a wave-storm–dominated delta front system. When correlated basinward, the two clinothems exhibit stratigraphic thickening as well as differing process responses to the increased gradient at the shelf-edge rollover. WfC 3 exhibits synsedimentary, wedge-shaped rotational growth faults. These growth faults trapped sand at the shelf-edge rollover, so minimal sand was delivered to the upper slope; therefore, the clinothem downlaps into the slope mudstones within 7 km of the shelf-edge rollover. In contrast, the top of WfC 4 is marked by closely spaced gullies cut into deformed delta front deposits. The delta front deposits pass into sand-prone slope turbidites 3 km downdip. Locally, these turbidites are truncated by a 60-m-thick turbidite-sandstone–filled slope channel fill. In this case, most of the slope delivery is associated with a wave-dominated process regime. It is important to consider the sequence stratigraphic setting of clinothems in such analyses; WfC 4 represents a minimum accommodation point in a depositional sequence and is overlain by a Type 2 sequence boundary. Despite wave and storm dominance, the low accommodation and high sediment supply at that time is interpreted to have driven sand beyond the gullied shelf-edge rollover. Therefore, the delivery of sediment to deep-water settings is governed by parameters other than the presence and proximity of a fluvial point source, which is heavily advocated in current models for shelf construction.


Having just killed the dragon, and with death 'ungemete neah' (2728b; 'exceedingly near'), Beowulf begins to speak, remarking first on his lack of a son: Nu ic suna minum syllan wolde guðgewædu, þær me gifeðe swa ænig yrfeweard æfter wurde lice gelenge. (2729–2732a) The language here seems almost neutral, but at least two of the terms are suggestive. The 'guðgewædu' ('war-garments') that he wishes to leave to his son recall most notably the elaborate gifts of weapons and horses – including the saddle that the king used in battle (1037b–1043) – that Hrothgar had given him following the fight with Grendel, implicating him, as John M. Hill and Stephanie Hollis have argued, in the Danish succession. Similarly, in using 'yrfeweard' ('guardian of an inheritance'), he calls attention to the king's role in protecting the tribe's wealth, although the poet may expect the audience to hear more in the compound since 'weard' appears often in the final part of the poem in descriptions of the dragon. Thus, even though Beowulf does not mention this failing again, his remark draws together a theme not only signficant in the Geatish section of the poem, but also present from the opening descriptions of Scyld's reign: part of a king's responsibility is to see that the succession is secure in a son.


Abstract Intuitionistic fuzzy set is a very useful tool to depict uncertainty. Lots of multi-criteria group decision making methods under intuitionistic fuzzy environment have been developed. Current methods are under the assumption that the criteria and the decision makers are at the same priority level. However, in real group decision making problems, criteria and decision makers have different priority level commonly. In this paper, multi-criteria group decision making problems where there exists a prioritization relationship over the criteria and decision makers are studied. First, the intuitionistic fuzzy prioritized weighted average (IFPWA) and the intuitionistic fuzzy prioritized weighted geometric (IFPWG) operators are proposed. Then, some of their desirable properties are investigated in detail. Furthermore, the procedure of multi-criteria group decision making based on the proposed operators is given under intuitionistic fuzzy environment. Finally, a practical example about talent introduction i...


The entry into force of the World Trade Organization (WTO) TRIPS Agreement in 1995 transformed the international intellectual property system. The harmonization of basic intellectual property standards has operated to protect investment in innovation, limiting risks from unjustified 'free riding'. Yet these same harmonized IP standards sharply curtailed the traditional capacity of suppliers of public goods, such as health care and nutrition, to address priority needs of less affluent members of society, particularly in (but not limited to) developing countries. In the Doha Declaration, the Waiver Decision of 30 August 2003 and the Article 31bis Protocol of Amendment, stakeholders concerned with re-opening policy space for the supply of newer pharmaceutical products pushed back against restrictive elements of the TRIPS Agreement.Governments around the world are in the process of deciding whether to ratify and accept the Article 31bis Amendment. Based on their Study for the International Trade Committee of the European Parliament, the authors argue that acceptance of the Amendment will provide a 'net benefit' for countries seeking to improve access to medicines. At the insistence of WTO delegations acting on behalf of the originator pharmaceutical industry lobby, Article 31bis regrettably is saddled with unnecessary administrative hurdles. Nonetheless, through skillful lawyering, political determination and coordinated planning, the system can be made to work. Among other options, expeditious back-to-back compulsory licensing linked with pooled procurement strategies may effectively achieve economies of scale in production and distribution of medicines.The authors doubt that the international political environment would support renegotiation of an 'improved' solution. They express concern that failure to bring the Amendment into force will open the door to a campaign to undermine the Waiver Decision. Recent events in Brazil and Thailand illustrate both the opportunities and risks associated with implementing TRIPS exception mechanisms, and help to inform views on the negotiating environment. Specific proposals for regional cooperation in implementing the Amendment are laid out, and the authors emphasize the importance of pursuing concrete transfer of technology measures in support of developing country pharmaceutical manufacturing. Over-reliance on private market mechanisms for the supply of public health goods leaves the international community with an unresolved collective action problem on a large scale. Oxford University Press 2007, all rights reserved, Oxford University Press.


Current forest restoration practices for New York City's (NYC) MillionTreesNYC Initiative on public parkland include site preparation with extensive invasive species removal and tree and shrub planting with the goal of creating new multi-layered forests. We have launched a longterm investigation of these sites in order to understand the primary physical, chemical, and biological responses of urban ecosystems to MillionTreesNYC forest restoration practices. This research will examine high and low diversity tree and understory planting combinations in permanent experimental forest restoration plots across NYC. The study assesses how the interactions between soil heterogeneity, plant population dynamics, and forest restoration management strategies drive urban forest ecosystem structure and functioning. Working in collaboration with the NYC Department of Parks & Recreation (NYC Parks) and the MillionTreesNYC tree planting campaign, we are examining different restoration strategies to assess how restoration practices affect the ecological development trajectories of newly established forests in NYC.


Performs a comprehensive experimental and theoretical investigation of methods for overcoming the excited-state absorption (ESA), which is the main obstacle to efficient pumping of erbium-doped fiber amplifiers (EDFAs) at 800 nm. The effects of ESA on gain can be reduced at the cost of an additional noise penalty by adopting bidirectional pumping or by pumping in the long-wavelength tail of the ground-state absorption (GSA) band. The GSA and ESA cross-section spectra on the glass host material. One of the most promising hosts, fluorophosphate, is compared to Al/P silica in a detailed analysis based on a quantitative numerical model. It is predicted that 2-3 dB less pump power is required for the fluorophosphate EDFA. For Al/P-silica EDFAs, it is found that approximately 7-dB-higher power is required when pumping in the 800 nm band than for pumping at 980 and 1480 nm. >


Abstract. Output from the regional climate model RACMO2/ANT is used to calculate the heat budget of the Antarctic atmospheric boundary layer (ABL). The main feature of the wintertime Antarctic ABL is a persistent temperature deficit compared to the free atmosphere. The magnitude of this deficit is controlled by the heat budget. During winter, transport of heat towards the surface by turbulence and net longwave emission are the primary ABL cooling terms. These processes show horizontal spatial variability only on continental scales. Vertical and horizontal, i.e. along-slope, advection of heat are the main warming terms. Over regions with convex ice sheet topography, i.e. domes and ridges, warming by downward vertical advection is enhanced due to divergence of the ABL wind field. Horizontal advection balances excess warming caused by vertical advection, hence the temperature deficit in the ABL weakens over domes and ridges along the prevailing katabatic wind. Conversely, vertical advection is reduced in regions with concave topography, i.e. valleys, where the ABL temperature deficit enlarges along the katabatic wind. Along the coast, horizontal and vertical advection is governed by the inability of the large-scale circulation to adapt to small scale topographic features. Meso-scale topographic structures have thus a strong impact on the ABL winter temperature, besides latitude and surface elevation. During summer, this mechanism is much weaker, and the horizontal variability of ABL temperatures is smaller.


The biochemical and biological mechanisms metastatic cancer cells use to function as communities and thwart internal and external growth control mechanisms remain undefined. In this work, we present the hypothesis that cancer cells may use a Quorum-Sensing mechanism to regulate multicellular functions and control steps in metastatic colonization. Quorum sensing is a bacterial cell-cell communication process used to track increasing cell-population density and, in response to changes in cell number, coordinate gene expression and behavior on a communitywide scale. Important parallels between the behavior of societies of bacterial cells and societies of malignant cancer cells exist in the bacterial literature. Of relevance to metastasis is the finding that pathogenic bacteria use quorum sensing to determine when their population numbers are high enough to collectively form biofilms in or on host organisms. Biofilms are complex, heterogeneous communities of bacterial cells encased within an extracellular matrix attached to a solid surface. Biofilms exacerbate disease and are refractory to a battery of therapies. We suggest that the quorum-sensing-controlled bacterial biofilm formation process closely parallels the steps in metastatic colonization. Cells migrate toward/on target surfaces (organ-specific homing), show cell-cell and cellmatrix interactions (tumor cell-stromal cell crosstalk), remain subclinical until they can mount an effective attack (dormancy), form complex structures with channels for nutrient flow (vascularized lesions), and contain resistant cells which can cause disease recurrence (persistors). Using ovarian cancer as an example, we present data supporting the connection between metastatic colonization and quorum sensing and discuss the implications for understanding and controlling metastasis formation.


A novel algorithm is introduced for estimating the echo path responses for stereophonic acoustic echo cancellation. When the Wiener solution for the echo path responses is non-unique, the echo paths are estimated in two stages. In a first stage, one of the non-unique Wiener solutions is estimated. Then in a second stage, a disturbance is introduced and the left and right misalignment vectors can be formulated as the Wiener solution with respect to the residual signals appearing after adding the d isturbance. The aim is to take advantage of the knowledge about the specific disturbance which is introduced. Adaptive algorit hms based on this two stage idea are used. It is shown with a series of numerical simulations that the proposed algorithm converges much faster than a corresponding conventional one stage adaptive algorithm.


There has already been written on the legal support service in the scientific works of Law University of Lithuania. The materials have emphasized that the legal support content lies in the cultural exchange among individuals and it is based on the law. Besides, there is a guarantee that individuals enjoy equal rights in cultural activities. While discussing the cultural level of society members we can not avoid the question of the level of legal relationship which is based on the Constitution of the Republic of Lithuania. Therefore, when using the method of comparable analysis we analyze the cultural interrelationship among people – the positive law, we should discuss the question of relationship between the law system in Lithuania and the cultural development of our society. While seeing the cultural development within the law system we need to analyze the legal structure of the Constitution of Lithuania as the example of the positive law. This analysis will let us look into the legal norms content of the constitution of the Republic of Lithuania and answer the following questions: – are the norms legal and equally representing the interests of all legal individuals? – do the norms give legal opportunity to the obligations and rights of individuals being the source of any civil law? If the answers were "yes", we could speak about the progress of culture in the field of law. The progress of culture in the field of law by no means will influence the progress in other cultural spheres of society life because cultural relations among people start, develop and end following the norms of the positive law. If those norms became legal (in respect of the relation between obligations and rights), the relations among individuals would lead to creative achievements with the initiative of different services. In the article we are going to analyze the legal structure, content and significance of norms in the Constitution of the Republic of Lithuania that was adopted in 1992 by the national referendum. The relationship of the Constitutional norms legal structure and the positive law, as well as the relationship between the progress of overall culture and the Constitution of democratic Lithuania is going to be determined too.


Iraqis of all ethnic and sectarian groups are fed up with the ineptitude and corruption of their political leaders and the institutions they control. Since 2015, they have turned out in record numbers to protest against their political elite. The protests that unfolded in 2015 and 2016 have highlighted two failings of Iraq's post-2003 "democratic" order: 1) the entrenchment of a corrupt "partyocracy" that has captured the state and deepened sectarian divisions, and 2) the weakness of state institutions and the absence of the rule of law that have encouraged widespread corruption and fostered broad popular distrust of the post-Saddam Iraqi state.


Rodents use active whisker movements to explore their environment. The "slip hypothesis" of whisker-related tactile perception entails that short-lived kinematic events (abrupt whisker movements, called "slips", due to bioelastic whisker properties that occur during active touch of textures) carry the decisive texture information. Supporting this hypothesis, previous studies have shown that slip amplitude and frequency occur in a texture-dependent way. Further, experiments employing passive pulsatile whisker deflections revealed that perceptual performance based on pulse kinematics (i.e., signatures that resemble slips) is far superior to the one based on time-integrated variables like frequency and intensity. So far, pulsatile stimuli were employed in a noise free environment. However, the realistic scenario involves background noise (e.g., evoked by rubbing across the texture). Therefore, if slips are used for tactile perception, the tactile neuronal system would need to differentiate slip-evoked spikes from those evoked by noise. To test the animals under these more realistic conditions, we presented passive whisker-deflections to head-fixed trained rats, consisting of "slip-like" events (waveforms mimicking slips occurring with touch of real textures) embedded into background noise. Varying the (i) shapes (ramp or pulse); (ii) kinematics (amplitude, velocity, etc.); and (iii) the probabilities of occurrence of slip-like events, we observed that rats could readily detect slip-like events of different shapes against noisy background. Psychophysical curves revealed that the difference of slip event and noise amplitude determined perception, while increased probability of occurrence (frequency) had barely any effect. These results strongly support the notion that encoding of kinematics dominantly determines whisker-related tactile perception while the computation of frequency or intensity plays a minor role.


Background:  Most people with disabilities the world over can be found in the Majority (or 'economically developing') World. This is also where most of the world's hungry and malnourished are found. We argue that the intersectionality between disability and nutrition may best be understood through a food security framework, and we position all people living with disability, including those experiencing feeding and swallowing disabilities, as at risk for food insecurity, especially those living in humanitarian emergency contexts. Objectives:  This study aimed to explore and describe the knowledge and experience of humanitarian aid workers (HAWs) and health care professionals (HCPs) in food assistance contexts with regard to the nutrition and food security of people living with disabilities. Method:  In this exploratory, descriptive study, 16 participants with experience in sub-Saharan Africa and Southern Asia participated in an online survey. Three survey participants with extensive experience were also interviewed. Data analysis involved descriptive statistics and thematic content analysis. Results:  Results revealed that participants had generally low levels of exposure to and experience with disability, including swallowing and feeding disorders. Conclusions:  Reduced knowledge of HAWs and HCPs regarding disability and the lack of professionals such as speech–language therapists, who manage disability-specific issues such as feeding and swallowing disorders, may affect the food security of people living with disabilities in food assistance contexts.


Analytic internal comparison of the Kikuyu, Kamba, and Mwimbi verbal systems requires detailed, systematic, and rigorously based presentation of points of similarity and dissimilarity. Over-emphasis or neglect of any dialect, area of the system, or point of similarity or dissimilarity would affect the validity of the comparison. Chapter I states the purpose of the investigation and specifies its field. Here are laid down the definitions and criteria underlying the analysis and providing for systematic and invariant presentation. This chapter also describes the general pattern of the four systems. Chapters II and III list the "endosyntactic unities", or sets of structurally identical constructions, for the "regular" and habitual/continuative systems, respectively. Chapter IV discusses the "morphologic unities", or sets of structurally identical morphemes, found as constituents of these endosyntactic unities. These chapters amount to a systematic presentation of patterned similarities between dialects, but also discuss points of difference. Chapters V and VI complete the comparison proper, describing unpatterned similarities and differences, respectively. It is interesting to note that only similarities seem to show systematic patterning; differences cannot be presented in such a framework. Chapter VII discusses the deductions possible from the results of comparison. Here it is found that few historical conclusions of probable validity can be drawn from the data. Chapter VIII summarizes and concludes the presentation. Appendices I-IV present the data on the four verbal systems which served as a basis for comparison. Appendix V gives the forms of subjective and objective prefixes, eliminated from the main comparison because of their numbers and because they belong to the nominal system, rather than the verbal. The comparison shows the systems are quite similar, though less than anticipated. It also illustrates the feasibility of comparison of verbal data, at least in these dialects by the methods and criteria used.


Many studies have documented the pervasive underfunding of public sector pension plans in the United States in recent years. The deterioration of the funded status of public pension plans coincided with severe fiscal crises that state and local governments experienced in the 2000s. This development has led to a suspicion that state and local governments have decreased employer pension contributions as a backdoor means of running fiscal deficits. In this paper, the authors investigate the extent to which this phenomenon has occurred. They estimate panel data regressions using the Boston College Center for Retirement Research's Public Plans Database, which provides data for 2001 through 2010. The authors find that contrary to popular belief, plan sponsors do not reduce their contributions in response to negative fiscal or economic shocks. In contrast, plan sponsors' contributions to their pension plans increase in response to growth in their unfunded liabilities. The authors document that the public pension underfunding crisis during the 2000s developed largely as a consequence of portfolio returns that fell short of expectations. Public pension plans' assets portfolios have a relatively high share of equities and other risky assets, leaving the plans' funded status vulnerable to asset price fluctuations. Although plan sponsors increased their contributions in response to the growth of unfunded liabilities, they did not do so by enough to fully counteract the effect of the subpar portfolio returns. This finding holds across the spectrum of plans ranked in terms of funded status in 2010.


These experiments investigate whether the facilitative effect of naming on the
acquisition of conditional discriminations in young children is due to enhancing
discrimination of the sample and comparison stimuli or whether naming serves additional
functions. Seventeen typically developing children, ages 4 to 6, were presented with a
three-choice arbitrary MTS AB conditional discrimination on Macintosh computers. The
participants were randomly selected to be in one of two sequences of conditions. The
conditions utilized in Experiment 1 were Tacting Condition 1 (naming sample stimuli);
Tacting Condition 2 (naming sample and comparison stimuli); Tally Sheet Condition 1
(marking sample stimuli); and Tally Sheet Condition 2 (marking sample and comparison
stimuli). The conditions utilized in Experiment 2 were Tacting Condition 1; Tacting
Condition 2; Cards Condition 1 (pointing to sample stimuli); and Cards Condition 2
(pointing to sample and comparison stimuli). Five participants acquired the AB
conditional discrimination; two did so without exposure to naming and without evidence
of common naming, and three did so with the addition of common naming. One
participant demonstrated evidence of common naming but did not acquire the AB
conditional discrimination. These results demonstrate that although naming can facilitate
acquisition, it is neither necessary nor sufficient.


Abstract. Biomass burning (BB) in southern Africa is the largest emission source of CO and O3 precursors within Africa during the West African Monsoon (WAM) between June and August. The long range transport and chemical processing of such emissions thus has the potential to exert a dominant influence on the composition of the tropical troposphere over Equatorial Africa (EA) and the Tropical Atlantic Ocean (TAO). We have performed simulations using a three-dimensional global chemistry-transport model (CTM) to quantify the effect that continental transport of such BB plumes has on the EA region. BB emissions from southern Africa were found to exert a significant influence over the TAO and EA between 10° S–20° N. The maximum concentrations in CO and O3 occur between 0–5° S near the position of the African Easterly Jet – South as placed by the European Centre for Medium range Weather Forecasts (ECMWF) meteorological analysis data. By comparing co-located model output with in-situ measurements we show that the CTM fails to capture the tropospheric profile of CO in southern Africa near the main source region of the BB emissions, as well as the "extreme" concentrations of both CO and O3 seen between 600–700 hPa over EA around 6° N. For more northerly locations the model exhibits high background concentrations in both CO and O3 related to BB emissions from southern Africa. By altering both the temporal resolution and the vertical distribution of BB emissions in the model we show that changes in temporal resolution have the largest influence on the transport of trace gases near the source regions, EA, and in the outflow towards the west of Central Africa. Using a set of trajectory calculations we show that the performance of the CTM is heavily constrained by the ECMWF meteorological fields used to drive the CTM, which transport biomass burning plumes from southern Africa into the lower troposphere of the TAO rather than up towards the middle troposphere at 650 hPa. Similar trajectory simulations repeated using an updated meteorological dataset, which assimilates additional measurement data taken around EA, show markedly different origins for pollution events and highlight the current limitations in modelling this tropical region.


Selection-based screening of large DNA-encoded libraries of drug-like small molecules is a validated method to identify bioactive compounds. Among the chemical space of bioactive compounds certain scaffold structures are well represented. These are commonly called "privileged scaffolds". We have synthesized DNA-encoded libraries based on two representatives of these scaffolds, a benzodiazepine and a pyrazolopyrimidine, and additionally a third library based on propargyl glycine. All three core structures possess a carboxylic acid to couple them to aminolinker-modified DNA. For subsequent library synthesis they contained an amino function to which a set of carboxylic acid building blocks were coupled, and a terminal alkyne that was reacted with a set of azides to furnish triazoles. The two sets of building blocks, 114 carboxylic acids and 104 azides, were selected with the help of chemoinformatic methods in order to control the physicochemical properties of the final libraries, remove unwanted substructures, and maximize diversity. The set of building blocks contained desthiobiotin allowing for validation of library synthesis. The DNA-encoded libraries were synthesized by split-and-pool combinatorial chemistry yielding three libraries that contain 28.254 compounds together. For DNA barcoding, 5′-phosphorylated double-stranded coding DNA sequences with four base overhangs were ligated with T4 ligase. The resulting DNA-encoded libraries were compared to bioactivity databases and, though being based on core structures well-established in medicinal chemistry, showed novelty with respect to the known bioactive chemical space.


FPGA-based heterogeneous Multiprocessor Systems-on-Chip (HMPSoCs) are becoming quite popular for high performance embedded systems because of their powerful computational ability and relatively flexible architecture to adapt to unexpected system requirement changes. However, with the insatiable demands of supporting an extensive range of applications beyond the limited resources of FPGA chip and shorter time-to-market, many research works on partially reconfigurable (PR) FPGA architectures have been conducted to fulfill the needs. Those have yet to fully provide a versatile framework to exploit the flexibility of PR such as hardware/software task migration and bitstream relocation; more importantly, the on-chip debug features to access all processors currently loaded in the system are compromised because of the lack of native-support from vendor tools. In this paper, a novel PR-HMPSoC architecture for dynamic FPGA-based embedded system is proposed to provide solutions for all of the above issues. The results from the experimental system consisting of one static Microblaze and three PR Microblaze/hardware accelerators connected by a Network-on-Chip show that the architecture is very promising with just 8% reduction in operating frequency.


Genevieve Lloyd's book is a provocative and accessible essay on the fragmentation of the self as explored in philosophy and literature. The past is irrevocable, consciousness changes as time passes: given this, can there ever be such a thing as the unity of the self? Being in Time explores the emotional aspects of the human experience of time, commonly neglected in philosophical investigation, by looking at how narrative creates and treats the experience of the self as fragmented and the past as 'lost'. It shows the continuities, and the contrasts, between modern philosophic discussions of the instability of the knowing subject, treatments of the fragmentation of the self in the modern novel and older philosophical discussions of the unity of consciousness. Being in Time combines theoretical discussion with human experience: it will be valuable to anyone interested in the relationship between philosophy and literature, as well as to a more general audience of readers who share Augustine's experience of time as making him a 'problem to himself'.


Since the early 1990s historical word formation, in particular derivation in Early Middle English, has increasingly attracted scholarly interest in the form of more general approaches to productivity and semantics. The present study focuses on the derivational patterns available to speakers and aims to identify factors which could influence the speakers' choices. For this purpose abstract formations in Early Middle English will be investigated, specifically (near) synonyms involving the Germanic suffixes -dom, -hood, -ness and -ship in which various suffixes can be attached to the same base without any or with only little differentiation in meaning. Abstract nouns ending in -lac, its Scandinavian cognate -leikr and -reden are also taken into consideration since – despite their subsequent, virtually complete demise – they still form an observable part of the lexicon and are represented in doublets such as fairness ~ fairleikr and fellowship ~ fellowreden. Regional and temporal variation, as well as the influence of text types, are shown to be factors which may have motivated the choice of suffixes in such synonymous derivations. The corpus-linguistic analysis is based on the Linguistic Atlas of Early Middle English, 1150–1325 (LAEME), the most recent corpus dedicated to the early period of Middle English. Owing to the patchiness of records, the texts are grouped in a way similar to the prototypical text categories proposed by the Helsinki Corpus in order to facilitate the comparison of data across space, time and text type. LAEME as a new research tool also offers an opportunity to re-examine previous statements which have to be amended in the light of new data.


In recent years there has been a development towards more complex forms of UN peacekeeeping. One example of this is the UN mission in former Yugoslavia (UNPROFOR), to which Sweden has contributed troops since 1992. A questionnaire study was conducted to gain information about the role of peacekeepers in this new kind of UN mission. The study includes data from four Swedish mechanized infantry battalions, which were deployed in Bosnia for six months each, from autumn 1993 to autumn 1995. The questionnaire was completed by a total of 3,505 persons in connection with the Swedish UN personnel demobilization procedures. This article presents some of their views and experiences and discusses these in relation to the role of peacekeepers in the 1990s.


Though Mary Parker Follett died in 1933, her philosophy of business organization and management is echoed in companies today where quality circles employee empowerment, and more horizontal organizational structures built on networks and relationships have been adopted with impressive results. Ahead of her time in the 1920s and 1930s, Follett was a political scientist, social work pioneer, speaker, and advisor to leaders concerned with labor-management relations on both sides of the Atlantic. Her advocacy of conflict as a constructive and creative means of problem solving and her general criticism of strict hierarchical structures in business organizations ran counter to the administrative dictates of the post-World War II era. Accordingly, her insights were neglected in the years following her death, and much of her work fell out of print. In Mary Parker Follett - Prophet of Management, editor Pauline Graham presents a selection of Follett's remarkable writings, culled from all her work, including her lectures. These, delivered between 1925 and 1933, provide a fascinating perspective on critical management topics that have continued relevance for managers today: conflict, power, authority, leadership, control, the role of the individual in the group, and the place of business in society. This collection brings together an eminent group of management experts from four continents and two generations who celebrate their own good fortune in having encountered Mary Parker Follett in the decades when her work was uncovered primarily through library research. Commentaries by Warren Bennis, John Child, Angela Dumas, Tokihiko Enomoto, Henry Mintzberg, Nitin Nohria, and Sir Peter Parker accompanyFollett's own words. Their reflections underscore the contemporary significance of Follett's ideas and testify to the excitement of discovering eloquence and truth in the observations of a brilliant thinker who continues to lead the way in her espousal of business as a social in


BACKGROUND
Stroke is a devastating condition encompassing a wide range of pathophysiological entities that include thrombosis, hemorrhage, and embolism. Current diagnosis of stroke relies on physician clinical examination and is further supplemented with various neuroimaging techniques. A single set or multiple sets of blood biomarkers that could be used in an acute setting to diagnosis stroke, differentiate between stroke types, or even predict an initial/reoccurring stroke would be extremely valuable.

CONTENT
We discuss the current classification, diagnosis, and treatment of stroke, focusing on use of novel biomarkers (either solitary markers or multiple markers within a panel) that have been studied in a variety of clinical settings.

SUMMARY
The current diagnosis of stroke remains hampered and delayed due to lack of a suitable mechanism for rapid (ideally point-of-care), accurate, and analytically sensitive biomarker-based testing. There is a clear need for further development and translational research in this area. Potential biomarkers identified need to be transitioned quickly into clinical validation testing for further evaluation in an acute stroke setting; to do so would impact and improve patient outcomes and quality of life.


Elevated concentrations of residual aluminium (Al) is an important issue for water treatment facilities. Concerns associated with high concentrations of residual aluminium include increased turbidity in drinking water, reduced effectiveness of disinfection, decreased carrying capacity of the water distribution system as well as potential effects on human health. The objectives of this study were to review the literature on mechanisms for controlling residual aluminium concentrations and to conduct a field study to evaluate the forms of residual aluminium in three water treatment plants. Both the literature review and results of the field study suggest that elevated concentrations of residual aluminium appear to occur largely in either of two forms; particulate aluminium or dissolved (monomeric) aluminium. To decrease concentrations of residual aluminium which largely occur as monomeric aluminium, it is necessary to maintain the pH of treated water near the pH of minimum Al(OH)3 solubility (6.5–7.0), remembering that this value varies with temperature. Elevated concentrations of residual aluminium associated with particulate aluminium may be due to influent suspensions with a high aluminium content or relatively large amounts of aluminium coagulant per amount of particulate matter in raw water. The results of this study suggest that filtered water turbidity should be less than 0.1 NTU to minimize particulate aluminium concentrations that contribute to residual aluminium.


We investigate geometric percolation and scaling relation s n suspensions of nanorods, covering the entire range of aspect ratios from spheres to ex tremely slender needles. A new version of connectedness percolation theory is i ntroduced and tested against specialised Monte Carlo simulations. The theory ac cur tely predicts percolation thresholds for aspect ratios of rod length to width as low as 10. The percolation threshold for rod-like particles of aspect ratios belo w 1000 deviates significantly from the inverse aspect ratio scaling prediction, thought t o be valid in the limit of infinitely slender rods and often used as a rule of thumb for na no-fibres in composite materials. Hence, most fibres that are currently used as fille rs in composite materials cannot be regarded as practically infinitely slender for the purposes of percolation theory. Comparing percolation thresholds of hard rods and n ew benchmark results for ideal rods, we find that (i) for large aspect ratios, they d iffer by a factor that is inversely proportional to the connectivity distance betwe en the hard cores, and (ii) they approach the slender rod limit differently.


The fluoride concentration of a borehole water supply in a rural area (Madibeng Local Municipality, North West Province, South Africa) varies between 5 and 6 mg/.. This water is therefore not suitable for potable purposes because the high fluoride concentration may cause mottling of tooth enamel in children and fluorosis in adults. Therefore, the fluoride concentration should be reduced to less than 1.5 mg/. to make the water suitable for potable purposes. The activated alumina and reverse osmosis processes are both processes that can be very effectively applied for water defluoridation. The activated alumina process, however, is considered to be a more simple and robust process for water defluoridation, especially in a rural area. Therefore, the activated alumina process was selected for water defluoridation. An activated alumina plant was designed, constructed and commissioned in the rural area. Fluoride in the feed water is removed from 6 to 8 mg/. to less than 1.5 mg/.. No reduction in plant output was experienced over 6 service cycles. Therefore, it appears that fouling of the activated alumina should not be a problem. Plant output varied between 940 and 1 296 m3 to a fluoride breakthrough of approximately 2.0 mg/.. No significant operational problems were experienced during commissioning and the plant is performing satisfactorily. Spent regenerant is disposed of into evaporation ponds. It was demonstrated that a 1st world technology could be effectively applied in a rural area with proper training and supervision of the operators. The capital and operational costs of the 200 m3/d defluoridation plant are estimated at approximately R1.2m. and R0.7/m3 treated water.


The purpose of this study is to research the concept of achievement orientation in architecture education throughout the education periods of students, and to render the findings sharable with students and education professionals. The findings were gathered through measuring the intrinsic motivations of students in their first year of architectural education and comparing the effect of these measurement results on the students' graduation year. The reason why the study steers towards the field of psychology is the thought that motivation is a necessary element for achieving success and affects architectural design education in a fundamental way. Motivation is a part of the emotional intelligence, an area which is now measurable in psychology.


Establishing strontium isotope (87Sr/86Sr) geographical variability is a key component of any study that seeks to utilize strontium isotopes as tracers of provenance or mobility. Although lithological maps can provide a guideline, estimations of bioavailable 87Sr/86Sr are often necessary, both in qualitative estimates of local strontium isotope "catchments" and for informing/refining isoscape models. Local soils, plants and/or animal remains are commonly included in bioavailability studies, although consensus on what (and how extensively) to sample is lacking. In this study, 96 biological samples (plants and snails) were collected at 17 locations spanning 6 lithological units, within a region of south-west France and an area with a high concentration of Paleolithic archaeological sites. Sampling sites aligned with those from a previous study on soil bioavailable strontium, and comparison with these values, and the influence of environmental and anthropogenic variables, was explored. Data confirm a broad correspondence of plant and snail 87Sr/86Sr values with lithological unit/soil values, although the correlation between expected 87Sr/86Sr values from lithology and bioavailable 87Sr/86Sr ratios from biological samples was higher for plants than for snails. Grass, shrub and tree 87Sr/86Sr values were similar but grasses had a stronger relationship with topsoil values than trees, reflecting differences in root architecture. Variability in 87Sr/86Sr ratios from all plant samples was lower for sites located on homogeneous geological substrates than for those on heterogeneous substrates, such as granite. Among environmental and anthropogenic variables, only an effect of proximity to water was detected, with increased 87Sr/86Sr values in plants from sites close to rivers originating from radiogenic bedrock. The results highlight the importance of analyzing biological samples to complement, inform and refine strontium isoscape models. The sampling of plants rather than snails is recommended, including plants of varying root depth, and (if sample size is a limitation) to collect a greater number of samples from areas with heterogeneous geological substrates to improve the characterizations of those regions. Finally, we call for new experimental studies on the mineralized tissues of grazers, browsers, frugivores and/or tree leaf feeders to explore the influence of 87Sr/86Sr variability with soil profile/root architecture on 87Sr/86Sr values of locally-feeding fauna.


AIM
This study used a multicenter questionnaire survey to evaluate the morphology and progression of the initial lesion in cases of colitis-associated colorectal neoplasia (CRN).

PATIENTS AND METHODS
Endoscopic images of lesions that had been definitively diagnosed as CRN by pathological examination were retrospectively reviewed.

RESULTS
This resulted in the identification of 54 initial lesions in 49 patients. The 54 initial lesions fell into the following categories: 22 endoscopically visible localized lesions consisting of 18 elevated lesions and 4 depressed lesions, as well as 32 lesions that were not endoscopically visible as localized and consisted of 20 active-phase mucosal lesions and 12 remission-phase mucosal lesions. Nineteen of the lesions eventually became advanced cancers, while 35 lesions eventually became early-stage cancers. The final lesions were 40 elevated lesions, 5 flat or depressed lesions and 9 stenotic lesions. The form of growth of the advanced cancers was progressive stenosis or increased elevation. For approximately 69% of the early-stage cancers, the growth form was increasing elevation or development of elevation. For 73.6% of the advanced cancers, the initial lesion underwent rapid growth and became advanced cancer within 3 years; they accounted for 25.9% of the total cancers. Approximately 40% of the initial lesions of CRN were endoscopically visible as localized lesions, while approximately 60% were judged to be inflammatory mucosal lesions.

CONCLUSION
It will be necessary to proactively take biopsy inflammatory mucosal lesions in order to discover tumors early and periodic surveillance should be performed with the knowledge that tumors may grow very quickly.


Receptor activator of nuclear factor κB ligand (RANKL) produced by regulatory T cells triggers the metastasis of breast cancer cells. Signaling by receptor activator of nuclear factor κB (RANK) in response to RANK ligand (RANKL) promotes the generation of osteoclasts. RANKL also stimulates the proliferation of mammary gland cells during pregnancy through activation of inhibitor of nuclear factor κB (NF-κB) kinase α (IKKα). Because the abundance of RANKL is increased in metastatic prostate cancer, Tan et al. investigated a role for RANKL in breast cancer metastasis. In a mouse model of breast cancer induced by the proto-oncogene Erbb2, heterozygosity in Rank had no effect on tumorigenesis but led to a 50% reduction in lung metastases compared with that in Erbb2/Rank+/+ mice. RANKL signaling induced the nuclear translocation of IKKα, and silencing of IKKα increased the number of apoptotic cells in late-stage tumors. Immunohistochemical analysis of Errb2-induced mammary tumors showed that RANKL was present in the stromal area of the tumor. CD4+ regulatory T cells (Tregs) localized to this same area, which also contained the chemokine CCL5, and tumor-infiltrating Tregs expressed the receptor for CCL5. Inoculation of CD4–/– mice with Errb2 tumor cells resulted in fewer lung metastases than occurred in inoculated wild-type mice. Transplantation of CD4+CD25+ Tregs restored the number of metastases in the CD4–/– mice, which was blocked with an antibody against RANK. RANKL increased the incidence of metastasis in nude mice that were inoculated with human breast carcinoma cells. Together, these data suggest that RANKL produced by tumor-infiltrating Tregs stimulates breast cancer metastasis, leading the authors to suggest that a combination of traditional therapy with targeting of RANK-RANKL signaling may reduce the extent of metastatic disease. W. Tan, W. Zhang, A. Strasner, S. Grivennikov, J. Q. Cheng, R. M. Hoffman, M. Karin, Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL-RANK signalling. Nature 470, 548–553 (2011). [PubMed]


Longitudinal light profile microscopy (LLPM) is introduced in this work as a new optical method for depth profiling the properties of thin-film materials. The method uses irradiation of an optically polished cross section of a prepared thin film sample, by a laser beam propagating along the depth (longitudinal) axis of the material. An observation microscope, aligned along an orthogonal axis to the sample cross section, transfers an image of the light profile propagating along the material's longitudinal (depth) axis to a recording camera. While depth attenuation of the optical beam in the sample is dominated by light absorption, and turbid scatter (which our analysis neglects), light profile images recovered by the microscope use contrast mechanisms based on luminescence and elastic or inelastic light scatter. Blur contributions to the images arising from axial thickness of the light profile "object" are shown to be minimal in our microscope. Our experimental setup, moreover, is constructed from relatively inexpensive, easily available components. A number of different image contrast mechanisms, including luminescence and elastic scattering contrast, were demonstrated on materials with known optical properties, including continuous media and laminates. The sample dimensions and depth-dependent image features were directly observable and unambiguous to identify. Images recovered on the basis of elastic scattering showed unusual contrast for optical interfaces in materials which were transparent at the analysis wavelength. The method holds promise for providing a plethora of new depth-resolved imaging mechanisms.


This document is part of a series of white papers on various copyright issues. One statute, 17 USC § 108, provides a number of exceptions specifically for libraries. In addition to fair use, there are a variety of other exceptions built into the copyright law that don't get as much attention.This paper specifically addresses one of 108's lesser-used provisions and the value it may hold for libraries and archives: 108(h).


The Emu Bay Shale Lagerstätte (Cambrian Series 2, Stage 4) occurs on the north coast of Kangaroo Island, South Australia. Over 50 species are known from here, including trilobites and non‐biomineralized arthropods, palaeoscolecids, a lobopodian, a polychaete, vetulicolians, nectocaridids, hyoliths, brachiopods, sponges and chancelloriids. A new chelicerate, Wisangocaris barbarahardyae gen. et sp. nov., is described herein, based on a collection of some 270 specimens. It is up to 60 mm long, with the length of the cephalic shield comprising about 30% that of the exoskeleton. The cephalic margin has three pairs of bilaterally‐symmetrical small triangular spines. A pair of small eyes is placed well forwards on the ventral margin of the cephalic shield. The trunk comprises 11 segments that increase in length while narrowing posteriorly, each possibly bearing a pair of biramous appendages; the most posterior segment is almost square whereas the others are transversely elongated. The spatulate telson is proportionately longer than in taxa such as Sanctacaris, Utahcaris and Leanchoilia. Up to eight (?four pairs) of 3 mm‐long elements bearing alternating inward‐curving short and long spines beneath the cephalic shield are interpreted as basipodal gnathobases, part of a complex feeding apparatus. A well‐developed gut includes a stomach within the cephalic shield; it extends to the base of the telson. In a few specimens there are shell fragments within the gut, including those of the trilobite Estaingia bilobata (the most common species in the biota); these fragments have sharp margins and extend across the gut lumen. The species may have been a predator or a scavenger, ingesting material already broken up by a larger predator/scavenger. The morphology of this taxon shares many overall body features with Sanctacaris, and some with Sidneyia, particularly its gnathobasic complex. These chelicerate affinities are corroborated by phylogenetic analyses.


This qualitative cross disciplinary research examined to what degree social presence was achieved through the use of a telepresence robot by one of the authors, in her capacity as a keynote speaker at an international research symposium. We explored if and how social presence was a factor in her ability to strategically position herself as a notable researcher whilst in 'telepresence mode', with the aim of understanding whether one could exercise the same degree of agency in telepresence mode as compared to appearing in person. We were also interested to know how those attending the symposium experienced having a tele present delegate in their midst. The research used an analytic framework based on Hassenzahl's (2014) ideas of "experience design" and his des cription of the "user experience" and evaluated the tele present person's ability to strategically position in a virtual environment by applying the analytical lens of Positioning Theory (Harre van Langenhove, 1999).Findings indicated it is possible to establish a high degree of social presence whilst in telepresence mode. This relates to both the telepresence robot product and the phenomenon of telepresence as experienced by the user and symposium attendees. However, while the user was able to position herself successfully all indicators were that social competencies also played a significant role in her being able to interact in telepresence mode. Attending international conferences using telepresence robots is potentially attractive for economic and ti me saving reasons, but little is understood about how delegates experience telepresence and whether conference attendance objectives can be achieved. We demonstrate how social presence is achieved both through the capabilities of the telepresence robot, bu t also through a combination of the amount of symbolic capital possessed by the user and the user's social competencies. This has implications for decision making in terms of who is likely to be able to successfully operate in tele present mode at such events.


This study investigates basic and extended meanings of Chinese motion/directional verbs, which are used frequently in metaphorical extensions. By looking at metaphorical uses in language, I hope to contribute to our understanding of the human conceptual system, which is assumed to be largely metaphorical in nature. One motion/directional verb in Chinese can combine with another to form a compound. Motion/directional verbs/compounds easily enter into a variety of larger constructions and they are frequently used with different senses. Cognitive Grammar (Langacker, 1987, 1988, 1991 & 2008) assumes that a single word is routinely polysemous in its various linguistic expressions. This paper will show that various senses of Chinese motion/directional verbs are actually related. I assume that extensions from the spatial domain to the temporal domain and from the concrete domain to the abstract domain could be found across motion/directional verbs. I will look at motivations behind extension patterns by addressing questions related to pairs of motion/directional verbs. Some verbs used frequently with one paired motion/directional verb are not likely to be compounded with the other due to their semantic (in)compatibility (Yin, 2010). Semantic and functional extensions may be based on a certain component of the total meaning of a lexical item while the other aspects of the meaning are non-salient. I argue that all the extensions are not random but motivated.


Different relative loads during resistance training movements are considered to result in varying physiological adaptions. The challenge facing coaches and athletes is how to determine what absolute load relates to the prescribed relative load and how to account for changes in strength. Velocity based training may offer a solution to this problem. Currently there are limited guidelines for coaches to follow and the proposed methods are associated with increased burden. Therefore, this article provides simple evidence based guidelines and an online application to support the use of velocity based training as a method of auto-regulation during resistance training.


Background Our group has been analysing routine operational data on A and E and UCC attendances with a focus on "frequent flyers" – those who attend 4 or more times per year. Aims To test the hypothesis that those who repeatedly attend fall into two main groups: chronic long standing illness (CLSI) and those who decide to attend A&E out of choice or preference. To describe the clinical characteristics of a subgroup attending very frequently. Method Retrospective analysis conducted on routine operational data collected for a large DGH. The data set included collated paediatric attendances to the Urgent care centre and paediatric A+E at the Hospital over a one-year period (01/10/13–30/09/14). A sub-group of those attending nine or more times was analysed. Results 10641 patients under 5 attended A&E in the time period, 753 attended 4 or more times, 33 attended 9 or more times (over a total of 337 attendances). Of these, 23% required admission and 77% and were discharged. Of the top 33 attenders 15 (45%) had a CLSI, (6, 18% multiple e.g ex-prem, Intraventricular haemorrhage and Chronic lung disease, 9, 27% single e.g. cleft palate). More than half 18 (55%) had no underlying chronic illness. In patients with chronic disease background admission risk was significantly higher Table 1. (Chi Sq 22.7, p = 0.00002) The most common diagnosis in the top 33 attenders was upper respiratory tract infection, followed by unspecified viral infection, acute bronchiolitis and intestinal infection. The top three diagnoses for the different patient groups are shown in Table 2.Abstract G341(P) Table 1Abstract G341(P) Table 2 Diagnoses made in admitted and discharged patients by underlying disease status Conclusion Frequent attenders can be characterised into two different groups, those with chronic underlying conditions and those without. We are exploring options to reduce repeat A&E/UCC attendance by those with chronic illnesses with additional community specialist nurse support and in both groups with parental and GP education particularly targeting the management of respiratory illness.


Territory is an important part of contemporary political debates but there is an odd silence about the concept of territory in contemporary political theory. The unraveling of colonization and concerns over global justice should make territory a central aspect of political theory, yet it is not. This silence has the curious feature of recalling the original justifications for territorial acquisition. Because territory is neglected by contemporary thinkers, it is important to return to theorists such as Grotius, Hobbes, Locke, Pufendof and Kant for a critical engagement with the concept of territory. Understanding the arguments of these thinkers illuminate the presuppositions of present day theorists and contributes to the understanding of contemporary theoretical problems. The thesis is organized into eight chapters. The first two chapters consider the neglect of territory in political theory the role of territory in international law. This sets up the three middle chapters which are critical engagements with historical thinkers organized around three conceptions of territory: territory as possession, as property and as jurisdiction. Contemporary cosmopolitanism is inspired, in part, by unraveling of colonization and a concern for global justice. Chapter 6 considers the relationship between contemporary cosmopolitanism and the legacy of the historical conceptions of territory. The next chapter investigates the communitarian critique of cosmopolitanism and the role of identity in territorial claims. At first glance there seems to be good reasons for contemporary theory to presuppose or ignore territory. However, the answer, though skeptical, is more subtle. Following Rawls and others, contemporary theory is right to remain silent about territory and about property in territory. The main skepticism is about arguments for colonial restitution or global redistribution of resources. This is because many take a crude territory as property view - which when abandoned seems to leave the world un-owned and therefore subject to equal distribution or claims. Yet skepticism is not the only alternative. Jurisdiction entails some elements of the territory as property view. This is a more sophisticated claim than the straight territory as property argument. Here ownership is a secondary but important claim states make in the absence of a binding universal norm. As a result there is a prima facie but not indefeasible right to particular territory. Identity plays a role in linking peoples to places. It also raises the bar to colonial restitution and global resource redistribution. This legitimates the current view of territory in political theory and international law where territory is pre-supposed but not theorized.


Purpose Hemodialysis is a treatment that is essential for the survival of patients with terminal chronic kidney disease. However, it is highly invasive, non-curative, and physically, psychologically, socially, and financially demanding, which has an impact on the patient's health-related quality of life (HRQL). In Colombia, research from the point of view of patients undergoing hemodialysis is scarce. Patients and methods We conducted a cross-sectional study involving 142 patients undergoing hemodialysis. We used an instrument that included the demographic and clinical information as well as the Charlson Comorbidity Index and Karnofsky Performance Status Scale. HRQL was assessed using EQ-5D-5L and KDQOL-36. The analysis was done using measures of central tendency for quantitative variables and relative frequencies for qualitative variables, in addition bivariate and multivariate regression analyses were conducted. Results Based on the scores of the EQ-5D-5L scale, it was found that 14.5% subjects showed severe mobility problems, 5.8% were unable to bathe or dress by themselves, 12.9% were unable to perform usual activities, 13.5% were experiencing pain or discomfort (between strong and extreme), and 58.6% showed a certain degree of anxiety or depression. The KDQOL-36 scores were 67.4 ± 19.4 for the symptoms domain and 35.0 ± 27.5 for the disease burden domain. Results of the linear regression analysis showed that the main factors associated with HRQL were the Karnofsky Index and serum albumin levels (p < 0.05). Conclusion The result of this study revealed the impact on the quality of life of Colombian patients undergoing hemodialysis with chronic kidney disease who were highly affected by the disease burden. KDQOL-36 has excellent properties of reliability, internal consistency, and discriminant power; thus, its use is recommended in subsequent studies to monitor HRQL in this population.


The new species Pycnolejeunea remotistipula from the state of Amazonas, northern Brazil, is described and illustrated. This species is characterized by sparsely-attached underleaves with obtuse lobes, a rounded leaf apex, large, and rectangular leaf lobules with free margin composed of more than six cells with thickened walls, elongated basal laminal cells forming a poorly differentiated vitta, as well as the absence of ocelli. A key to the Brazilian species of Pycnolejeunea is given.


The windows and doorways that connect offices to public spaces are a site for people to gather awareness information and initiate interaction. However, these portals often reveal more information to the public area than the office occupant would like. As a result, people often keep doors and window blinds closed, which means that nobody can gather awareness information, even those with whom the occupant would be willing to share. One solution to this problem is a co-present media space - a computer-mediated video connection at the boundary between an office and a public area. These systems can provide both greater privacy control to the occupant and greater overall awareness information to observers. To see how co-present media spaces would work in real world settings, we built what we believe are the first ever co-present media spaces, and deployed them in two offices. From observations gathered over fifteen months, it is clear that the systems can do a better job of balancing the occupant's need for privacy and the observers' need for awareness better, than a standard window. However, we also identified a number of issues that affected the use and the success of the systems: the existence of alternate information sources, confusion with existing social norms, disparities between effort and need, and reduced interactional subtlety for observers in the public area. Our work contributes both a novel arrangement of a media space for co-present collaborators, and the first investigation into the design factors that affect the use and acceptance of these systems.


This report represents a Phase III effort to design and evaluate a new sign design for incident route trailblazing. The colors evaluated were fluorescent coral, fluorescent purple, fluorescent yellow-green, and non-fluorescent purple. The results indicate no significant differences in driving performance with regard to the four experimental sign color combinations. Regarding the subjective preference questionnaires, significant questionnaire results along with trend information suggest that black on fluorescent yellow green was the most preferred by younger and older drivers during both day and night visibility conditions. Nonetheless, this sign color has been assigned by FHWA for pedestrian, school, and bicycle crossings, which eliminated the opportunity to use fluorescent yellow-green as a unique sign color for trailblazing in incident management situations. Preference for non-fluorescent yellow on purple consistently increased at night when the sign became more luminant; however, the overall preference for this sign color combination was lower than for the other sign color combinations tested in this study. With the elimination of these two signs, the remaining contenders for a unique sign color combination were black on fluorescent coral and fluorescent yellow on fluorescent purple. Black on fluorescent coral was ranked significantly higher than fluorescent yellow on fluorescent purple for visibility and for overall preference. Questionnaire trend information suggests that black on fluorescent coral was more preferred than fluorescent yellow on fluorescent purple during daytime viewing conditions and less preferred than fluorescent yellow on fluorescent purple during nighttime viewing conditions. The overlay film used for the fluorescent coral sign was a first generation material that can reasonably be expected to result in improved nighttime luminance when produced in a full production run. In addition to the study results, drivers commented that the arrow on the sign was too small to determine directional information from a comfortable distance. Based on such driver comments, the research conclusions, and the federal regulations enacted since the outset of this series of experiments, the following recommendations are made: (1) black on fluorescent coral should be used as a unique incident management sign color, and (2) the directional arrow on the sign should be larger.


Conformant planning can be formulated as a path-finding problem in belief space where the two main challenges are the heuristics to guide the search, and the representation and update of beliefs. In the translation-based approach recently introduced by Palacios and Geffner, the two aspects are handled together by translating conformant problems into classical ones that are solved with classical planners. While competitive with state-of-the-art methods, the translation-based approach runs however into three difficulties. First, complete translations are expensive for problems with high width; second, incomplete translations can generate infinite heuristic values for problems that are solvable; and third, aspects that are specific to the conformant setting, such as the cardinality of beliefs, are not accounted for.In this work, we build on the translation-based approach but not for solving conformant problems with a classical planner but for deriving heuristics and computing beliefs in the context of a standard belief-space planner. For this, a novel translation KSi is introduced that is always complete, but which is sound for problems with width bounded by i. A new conformant planner, called T1, builds then on this translation for i=1, extending the heuristic that results with a second heuristic obtained from invariant "oneof expressions". A number of experiments is performed to compare T1 with state-of-the-art conformant planners.


This study is based on several assumptions: it recognises that the person who is deformed has an existence both in the world and in the novel; it recognises that in both the world and the novel the deformed-being has borne a negative
stigma. It also recognises that a literature reflects its culture, as must the characters who exist within that literature. As Harry Heseltine states succinctly: 'No writer invents his metaphors ex nihilo; in the long run he finds them somewhere in the range of possibility that his culture makes available to him'. This study asks: can that most marginalised of all characters, the deformed-being, provide any revelations about the self, about the novel, the reader of the novel, and the culture within which all exist? The answer in each case is an unequivocal yes. Each chapter is devoted to a particular character in a major Australian novel; comparisons are made with other literary works, Australian and non- Australian. The individual chapters reveal the metaphors and symbolism attached to the character's particular deformity, and demonstrate how the deformed body informs the body of the text. The whole study presents an overall picture of deformity as a fairly consistent and an often-utilised metaphor. Chapter One provides a general survey of deformity as a metaphor. Chapter Two looks at Louis Stone's Jonah (1911), in which the hunchbacked larrikin character is a post-colonial interpretation of the traditionally conjoined outcast states, deformity and criminality. In Chapter Three the dwarf Jackie in Ruth Park's Swords and Crowns and Rings (1977) is seen as a metaphor for non-conformity during a time when Australia was signalling a resistance to the Old-World moulding. Chapter Four is also concerned with the post-colonial identity as revealed through the dwarf and half-caste Billy Kwan in C. J. Koch's The Year of Living Dangerously (1978); it questions an identity that is 'imposed', whether at a national or individual level. In Chapter Five the relationship of the hunchbacked dwarf Rhoda Courtney with her adopted brother, the artist Duffield, in Patrick White's The Vivisector (1970) places deformity in the tradition of the kunstlerroman. In Chapter Six, Koch's The Doubleman (1985) is shown to combine elements of the kunstlerroman while raising questions about the post-colonial identity through the dualities arising out of the doppelganger: spiritual, bodily, and cultural displacement are all focussed by the device of Richard Miller's lameness. Chapter Seven moves from deformity that is congenital or disease-originated, to disability or deformity that is human- caused (either by negligence or intervention), thus allowing a discussion of the importance of the etiology of deformity as a device: in Thea Astley's The Acolyte (1972) Jack Holberg's blindness is caused by fly-strike. Chapter Eight examines the use of terror evoked through archetypal evolution of the lame crone Hester Harper in Elizabeth Jolley's The Well (1985). In Chapter Nine the crypto-dwarf Arthur Blackberry in James McQueenls Hook's Mountain (1982) is portrayed with the accompanying baggage of dwarf mythology; his implicit demise raises questions about our responses towards the deformed. Chapter Ten is a literary history of eugenics, as seen primarily through Eleanor Dark's Prelude to Christopher (1934) and Christina Stead's The Man Who Loved Children (1940). The conclusion discusses the initial, problems of dealing with a taboo topic, along with reasons for excluding autobiographicaltreatments of deformity, biographical portrayals, war novels, and children's literature. Finally, Leslie Fiedler's comment that deformity is the reigning metaphor of our age is shown to be particularly apt in an Australian context.


I. INTRODUCTIONImagine that you're out with friends or that special someone on a Saturday enjoying a glass of wine at the new local winery. You see an interesting flavor and decide to give it a try. It tastes wonderful and you know it'll make the perfect holiday gift for friends. You're dreams of an easy Christmas shopping season have come true until you go talk to the owner about shipping. He pulls out a chart and starts to talk about which state and or town they're in, as well as the volume to be shipped and if your friends have visited the winery before. If you're puzzled and confused, you're not alone. As an attorney I wondered, how can such a varied regulatory structure exist under the commerce clause? You can ship to one state, but not another. You can even ship only to certain zip codes or towns within a state. Then, you have to worry about taxes, licenses and volume limitations on a state by state basis. One writer summed up the situation perfectly saying that "when it comes to buying wine, or any other alcoholic beverage, Americans may as well live in 50 different countries - some relatively free and open, some so closed they resemble old-style dictatorships."1 Though the focus of this paper is on the commerce clause and regulatory chaos that wineries, especially small ones, are forced to navigate, interstate shipping issues can arise with other products, such as tobacco, firearms, food and wildlife. The direct interstate shipment of wine is different from these in the fact that the major regulatory hurdles are state based, whereas the others are largely federally driven.2Taking a deep look into the regulatory difficulties the wine industry faces has become increasingly relevant due to the rapid growth of small wineries and increasing wine consumption in the United States. Nationally, the total number of wineries in the United States has more than doubled in the last 10 years, from 3,469 in 2002 to 7,881 as of early January, 2012.4 Even in California, a state already renowned for its wineries, the growth rate is nearly the same, growing from 1,704 wineries in 2002 to 3,364 in 2010. Perhaps the most explosive growth in the number of wineries is in my home state of Texas. In researching potential date night activities last fall, my wife and I were amazed to discover that there were now three wineries right in our "backyard" in the small village of Salado, Texas.5 According to Texas Alcoholic Beverage Commission (TABC) statistics, there were forty-six wineries operating in the state in 200 1.6 As of March 2012, there are 247 wineries; approximately a 500% growth rate over eleven years.7As the numbers of wineries have grown nationally, the quantities produced have grown as well. In 2002, the United States produced roughly 551.7 million gallons of wine. By 2010, that number had grown to 677.5 million gallons equating to an increase of 23%. Taking California out of the equation, the rest of the United States has seen an increase of production from 60.4 million gallons of wine in 2002 to 71 million gallons in 2010. This increase of 17.5% over eight years is still substantial, but behind California's growth. It should be noted, however, that 2010 was not the record production year for the United States, as environmental conditions and other variables can impact the annual production.9 Taking into account these variables, general trends are most relevant versus single year snapshots. When you contrast nearly a 100% growth rate for wineries in the United States against a 23% growth in wine production, the conclusion can be drawn that many of the new wineries are "small wineries" most impacted by the current chaotic regulatory environment discussed below.10II. FEDERAL IMPACTS - THE CONSTITUTION, THE COURTS AND CONGRESSThe starting point for the current regulatory framework in the direct shipment of wine is the commerce clause of the Constitution. Article I, Section 8 states, "Congress shall have power. …


In today's business environment, many companies want to become efficient and flexible, but have struggled, in part, because they have not been able to formulate optimal supply chain strategies. Often this is as a result of insufficient knowledge about the costs involved in maintaining supply chains and the impact of the supply chain on their operations. Hence, these companies find it difficult to manufacture at a competitive cost and respond quickly and reliably to market demand. Mismatched strategies are the root cause of the problems that plague supply chains, and supply-chain strategies based on a one-size-fits-all strategy often fail. The purpose of this article is to suggest instruments to determine an optimal supply chain strategy. This article, which is conceptual in nature, provides a review of current supply chain strategies and suggests a framework for determining an optimal strategy.


We performed a feasibility and safety study (phase II) of nicardipine, a calcium antagonist, in 57 patients. The objectives of the study were to begin therapy as early as possible (less than or equal to 12 hours) after the onset of ischemic stroke and to administer as high a dose as possible. All patients received an intravenous infusion of nicardipine for 72 hours, starting with a dose of 3 mg/hr and increasing to a maximum dose of 7 mg/hr. Upward titration of the dose was limited by a 10% decrease in blood pressure or a 20 beats/min increase in pulse. Intravenous therapy was followed by 30 days of oral therapy. The mean +/- SD interval from onset of stroke to commencement of therapy was 9.1 +/- 5.4 hours. Adverse reactions consisted primarily of hypotension requiring discontinuation of therapy in four patients. Score on a graded neurologic examination increased from 41/100 at baseline to 64/100 at 3 months for the 41 patients completing follow-up. There was no correlation between the dose of nicardipine administered and outcome, but the 11 patients starting therapy less than or equal to 6 hours after onset did better than those starting therapy 6-12 hours after onset. Further study of very early therapy with nicardipine is justified.