In Die Sprachen Europas in systematischer Uebersicht (Bonn 1850) Schleicher works out a naturalistic conception of language and a research program inspired by the methods of the natural sciences, in particular botany and geology. It does not only provide a general exposition of Schleicher's views, of the sharp lines he is drawing between linguistics and philology, of the concept of 'Sprachengeschichte' in contradistinction to 'Sprachentwicklung', of the methodology of linguistic research, but also – often overlooked – with an attempt at language typology. Inspired by proposals made by Friedrich and August Wilhelm Schlegel and Wilhelm von Humboldt, Schleicher tries to provide a material, scientific basis for language classification. In addition to this edition, the volume contains an introductory article.


Decreased erythropoiesis and increased clearance of both parasitized and noninfected erythrocytes both contribute to the pathogenesis of anemia in falciparum malaria. Erythrocytes with reduced deformability are more likely to be cleared from the circulation by the spleen, a process that is augmented in acute malaria. Using a laser diffraction technique, we measured red blood cell (RBC) deformability over a range of shear stresses and related this to the severity of anemia in 36 adults with severe falciparum malaria. The RBC deformability at a high shear stress of 30 Pa, similar to that encountered in the splenic sinusoids, showed a significant positive correlation with the nadir in hemoglobin concentration during hospitalization (r = 0.49, P < 0.002). Exclusion of five patients with microcytic anemia strengthened this relationship (r = 0.64, P < 0.001). Reduction in RBC deformability resulted mainly from changes in unparasitized erythrocytes. Reduced deformability of uninfected erythrocytes at high shear stresses and subsequent splenic removal of these cells may be an important contributor to the anemia of severe malaria.


Presented here is a review of present knowledge of the long-term behavior of solar activity on a multi-millennial timescale, as reconstructed using the indirect proxy method. The concept of solar activity is discussed along with an overview of the special indices used to quantify different aspects of variable solar activity, with special emphasis upon sunspot number.Over long timescales, quantitative information about past solar activity can only be obtained using a method based upon indirect proxies, such as the cosmogenic isotopes 14C and 10Be in natural stratified archives (e.g., tree rings or ice cores). We give an historical overview of the development of the proxy-based method for past solar-activity reconstruction over millennia, as well as a description of the modern state. Special attention is paid to the verification and cross-calibration of reconstructions. It is argued that this method of cosmogenic isotopes makes a solid basis for studies of solar variability in the past on a long timescale (centuries to millennia) during the Holocene.A separate section is devoted to reconstructions of strong solar energetic-particle (SEP) events in the past, that suggest that the present-day average SEP flux is broadly consistent with estimates on longer timescales, and that the occurrence of extra-strong events is unlikely.Finally, the main features of the long-term evolution of solar magnetic activity, including the statistics of grand minima and maxima occurrence, are summarized and their possible implications, especially for solar/stellar dynamo theory, are discussed.


The purpose of this exploratory study was to identify the key predictors of prostate cancer; such study may lead to the development of appropriate interventions and prevention. Previous epidemiological studies have found these following factors to be key predictors for being diagnosed with hormone-associated carcinoma such as prostate cancer: age, ethnicity, physical activity, family history, diet, sleep amount, marital status, and having another form of carcinoma. Many studies have included results only for men over the age of 65, however, prostate cancer is claiming the lives of many African American, Hispanic and White American men over the age of 35, and younger men are more likely to battle it if they are genetically predisposed. The sample population (N =21,646) was selected because men aged 35 or over has the highest prevalence of prostate cancer. Of this sample, 619 reported having prostate cancer, and 1,401 reported having some other type of cancer. This study employs a logistic regression model using SAS® and utilizes the National Health Interview Survey data set and a multivariate analysis of the years 2006, 2007, and 2008. To improve the quality of future research the methods need modification, the subpopulation being studied should be larger, and the studies should be longitudinal. This particular study found the aforementioned factors to be critical in predicting prostate cancer. Maximum sun exposure was also found to be related to prostate cancer. Key predictors for prostate cancer diagnosis are: age, ethnicity, having some other cancer and maximum sun exposure, and education. Though previous studies have found physical activity, sleep amount, and occupation to be beneficial in reducing the risk for prostate cancer, it was not confirmed in this particular study


STATCOM can provide fast and efficient reactive power support to maintain power system voltage stability. In the literature, various STATCOM control methods have been discussed including many applications of proportional-integral (PI) controllers. However, these previous works obtain the PI gains via a trial-and-error approach or extensive studies with a tradeoff of performance and applicability. Hence, control parameters for the optimal performance at a given operating point may not be effective at a different operating point. This paper proposes a new control model based on fuzzy control, which can self-adjust the control gains during a disturbance such that the performance always matches a desired response, regardless of the change of operating condition. Since the adjustment is autonomous, this gives the plug-and-play capability for STATCOM operation. In the simulation test, the adaptive PI control shows consistent excellence under various operating conditions, such as different initial control gains, different load levels, and change of transmission network, consecutive disturbances, and a severe disturbance. In contrast, the conventional STATCOM control with tuned, usually perform fine in the original system, but may not perform as efficient as the proposed control method when there is a change of system conditions.


Recent increase in political and funding commitments to malaria control have resulted in rapid scale up of indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) as priority vector control interventions. Despite this increasing coverage and consequent substantial reductions of malaria burden, residual malaria transmission by outdoor-biting mosquitoes in particular, necessitates complimentary vector control strategies such as larval source management. More sensitive and scalable entomological surveillance tools are required to monitor the resultant lower transmission levels that persist across much of the tropics. The Urban Malaria Control Program (UMCP) in Dar es Salaam, Tanzania, implements a large-scale community-based (CB) larviciding programme with the aim of demonstrating operational feasibility of integrating larval control into routine municipal services, while utilizing community-owned resource personnel (CORPs) for its implementation.
The goal of this study was to a better understanding of community participation in larval-stage vector surveillance and control, and to develop a practical, safe and affordable prototype for routine programmatic adult mosquito surveillance. Qualitative methods involving administering a set of unstructured interviews to CORPs were used to investigate their performance and demographic characteristics, their perceptions and reasons for participating in the UMCP. Ethnographic and historical resources were used to examine how 'participation in' and 'responsibility for' larval control is inter-articulated through scientific protocols, development practices, and the specific political history of Tanzania. Cross-sectional surveys were later used to assess the effectiveness of operational, community-based larval habitat surveillance systems within the UMCP by estimating the respective detection coverage and sensitivity levels by CORPs. Additionally, an intensive and extensive CB system for routine, longitudinal, programmatic surveillance of mosquitoes using the Ifakara Tent Trap (ITT) was developed and evaluated in comparison with quality assurance (QA) surveys using either ITT or human landing catches (HLC) and with malaria parasite prevalence from the cross-sectional surveys.
Overall, CORPs' individual detection coverage and sensitivity levels were poor, influenced by his/her unfamiliarity with the area, habitat type, fencing and inclusion within larviciding roll out. These indicators were particularly low among CORPs recruited through programme management staff, compared to those recruited by local government officials or health committees, and among staff living outside their areas of responsibility. The CORPs perceived their role to be professional rather than voluntary, with participation being a de facto form of employment. In spite of all challenges, the central coordination role played by the city council, coupled with catalytic donor funding and technical support from expert research partners, enabled institutionalization of strengthened management and planning and improved community mobilization. Capacity to exploit national and international funding systems was enhanced and a sustainable implementation program was ultimately established with funding from the Ministry of Health and Social Welfare, overseen by the National Malaria Control Programme and implemented by the City and Municipal Councils. Management of this program is currently supported by a spatially extensive and temporally intensive community-based longitudinal adult mosquito vector surveillance system with predictive power for parasite infection risk.


Silviculture treatments can alter landscapes, which in return can affect wildlife communities. This research examined how microhabitat differed short-term (1-2 years after disturbance) between two different oak-regenerating shelterwood treatments, a midstory-reduction (oak-shelterwood) and a first-harvested basal area removal (shelterwood), in comparison to undisturbed controls. Mechanisms responsible for influencing herpetofaunal communities were examined in the oak-hickory hardwood forests of the mid-Cumberland Plateau in Grundy County of Southern TN. Herpetofauna were captured using drift fences equipped with pitfall and box funnel traps, and microhabitat variables were collected at each trap location. Shelterwood stands had a higher amount of slash, slash pile volume, and woody and herbaceous vegetation than other stand types.Oak-shelterwood and control stands had higher litter depth, litter cover, and presence of overstory than shelterwood stands. Eastern fence lizards, eastern five-lined skinks, Fowler's toads and broad-headed skinks were all significantly more abundant in stands that received manipulation in comparison to control stands.


Negotiations are a relevant and highly complex business skill. Therefore, extensive training is required to become a good negotiator. Such training is offered by universities for their students and by companies for their employees. The present paper designs gamified feedback features in electronic negotiation training and evaluates their potential and their effects. Following a design science research method, feedback mechanisms in electronic negotiation training are derived from literature. An assessment regarding their relevance for e-negotiation training shows a preparation quiz, set and track goals and expert reviews to be the most useful gamified feedback mechanisms. Dedicated mock-ups implementing these feedback mechanisms are designed and evaluated in semi-structured interviews showing their capability to improve relevant negotiation skills, as well as motivation and competence of the learners. Out of the three mock-ups, the interviewees prefer the feedback mechanisms "expert review" and "set and track goals"; both mechanisms provide a competence-confirming learning experience and an autonomous learning experience.


In recent years significant numbers of Australian goats have been harvested from the feral population to supply a strong demand for export of meat. In addition large numbers of feral does have been domesticated to increase breeding herds in western Queensland. Introduction of the Boer breed to Australia as a specialist meat goat may provide a genetic means for improving the productive performance of the Australian feral. The present paper reports growth and carcase attributes of feral and Boer x feral genotypes born in 1998 and birthweight of those born in 1999.

Animal production for a consuming world : proceedings of 9th Congress of the Asian-Australasian Association of Animal Production Societies [AAAP] and 23rd Biennial Conference of the Australian Society of Animal Production [ASAP] and 17th Annual Symposium of the University of Sydney, Dairy Research Foundation, [DRF]. 2-7 July 2000, Sydney, Australia.


Modern advances in space technology have enabled the capture and recording of unprecedented volumes of data. In the field of solar physics this is most readily apparent with the advent of the Solar Dynamics Observatory (SDO), which returns in excess of 1 terabyte of data daily. While we now have sufficient capability to capture, transmit and store this information, the solar physics community now faces the new challenge of analysis and mining of high-volume and potentially boundless data sets such as this - a task known to the computer science community as stream mining. In this paper, we survey existing and established stream mining methods in the context of solar physics, with a goal of providing an introductory overview of stream mining algorithms employed by the computer science fields. We consider key concepts surrounding stream mining that are applicable to solar physics, outlining existing algorithms developed to address this problem in other fields of study, and discuss their applicability to massive solar data sets. We also discuss the considerations and trade-offs that may need to be made when applying stream mining methods to solar data. We find that while no one single solution is readily available, many of the methods now employed in other data streaming applications could successfully be modified to apply to solar data and prove invaluable for successful analysis and mining of this new source.


On the basis of general theories of Fourier self-deconvolution and curve fitting, an objective procedure to obtain the deconvolution parameters halfwidth, σ, and breaking point, L, is described. In the curve fitting routine, the analytical accessible line shape functions, derived for different apodization functions, are used to simulate the deconvoluted spectra. The fully automated deconvolution program was applied to the IR spectra of the amide I band of dry protein films to determine the secondary structure content.


The unusual form of sexual signaling, the drumming produced by the wolf spider Hygrolycosa rubrofasciata, allows exceptionally detailed studies of female preference patterns against signal characteristics. It is easy to manipulate the signals and to use large numbers of females in playback experiments. Males of H. rubrofasciata produce drums by striking their abdomen against dry leaves on the ground. Drums travel not only as substrate-borne vibrations, but also as airborne acoustic signals. Females respond sooner to drums transferred as substrate borne, but the mode of signal transfer has no effect on female preference for different types of drums. We investigated the effects of two key components of the drums, duration and pulse rate, on female choice. Previous studies have shown that the duration of the drum is both repeatable within males and variable between males. In contrast, pulse rate shows high within-male repeatability but only little variability between males. Using playbacks of manipulated drums, we found that females preferred drums of longer duration but that pulse rate had no effect on female preference. Our results suggest that drum duration may function as an indicator of male quality for choosy females. Pulse rate, on the other hand, is less likely to be an important trait in intersexual selection. Female preference for drum duration was open-ended within the natural variation of the drum durations, but it leveled off outside the normal range. Thus supernormal stimuli would not pay for males using this energetically demanding acoustic signal. Key words: acoustic signaling, drum duration, female choice, Hygrolycosa rubrofasciata, pulse rate, sexual selection, wolf spiders. [Behav Ecol 13:615–621 (2002)]


How much data is needed for calibration of a hydrological catchment model? In this paper we address this question by evaluating the information contained in different subsets of discharge and groundwater time series for multi‐objective calibration of a conceptual hydrological model within the framework of an uncertainty analysis. The study site was a 5·6‐km2 catchment within the Forsmark research site in central Sweden along the Baltic coast. Daily time series data were available for discharge and several groundwater wells within the catchment for a continuous 1065‐day period. The hydrological model was a site‐specific modification of the conceptual HBV model. The uncertainty analyses were based on a selective Monte Carlo procedure. Thirteen subsets of the complete time series data were investigated with the idea that these represent realistic intermittent sampling strategies. Data subsets included split‐samples and various combinations of weekly, monthly, and quarterly fixed interval subsets, as well as a 53‐day 'informed observer' subset that utilized once per month samples except during March and April—the months containing large and often dominant snow melt events—when sampling was once per week. Several of these subsets, including that of the informed observer, provided very similar constraints on model calibration and parameter identification as the full data record, in terms of credibility bands on simulated time series, posterior parameter distributions, and performance indices calculated to the full dataset. This result suggests that hydrological sampling designs can, at least in some cases, be optimized. Copyright © 2009 John Wiley & Sons, Ltd.


Research suggests that math and test anxiety have detrimental impacts on performance in math. To prevent these effects, a number of interventions have been developed, but these interventions have not been extensively tested. In the current study, we examine whether four brief anxiety interventions reduce state anxiety and/or increase math performance. We also examine whether any of the interventions weaken the relation between math or test anxiety and math performance. Participants were 300 college students varying in math and test anxiety levels. Participants were randomly assigned to one of four single-session interventions, which each took 5 minutes or less (reappraisal as challenge, reappraisal as excitement, expressive writing, and look ahead), or a no intervention control group. Results generally show that none of the interventions had an effect on reports of state anxiety or performance on a difficult math assessment, with the exception that students in the expressive writing condition reported higher levels of state anxiety. None of the interventions served to attenuate the relation between math or test anxiety and math performance. These findings were not consistent with results of previous work, and suggest that interventions may need to be more extensive in order to have an effect on state anxiety and math performance.


Users increasingly interact with a heterogeneous collection of computing devices. The applications that users employ on those devices, however, still largely provide user experiences that assume the use of a single computer. This failure is due in part to the difficulty of creating user experiences that span multiple devices, particularly the need to manage identifying, connecting to, and communicating with other devices. In this paper we present an infrastructure based on instant messaging that simplifies adding that additional functionality to applications. Our infrastructure elevates device ownership to a first class property, allowing developers to provide functionality that spans personal devices without writing code to manage users' devices or establish connections among them. It also provides simple mechanisms for applications to send information, events, or commands between a user's devices. We demonstrate the effectiveness of our infrastructure by presenting a set of sample applications built with it and a user study demonstrating that developers new to the infrastructure can implement all of the cross-device functionality for three applications in, on average, less than two and a half hours.


The popular Q-learning algorithm is known to overestimate action values under certain conditions. It was not previously known whether, in practice, such overestimations are common, whether they harm performance, and whether they can generally be prevented. In this paper, we answer all these questions affirmatively. In particular, we first show that the recent DQN algorithm, which combines Q-learning with a deep neural network, suffers from substantial overestimations in some games in the Atari 2600 domain. We then show that the idea behind the Double Q-learning algorithm, which was introduced in a tabular setting, can be generalized to work with large-scale function approximation. We propose a specific adaptation to the DQN algorithm and show that the resulting algorithm not only reduces the observed overestimations, as hypothesized, but that this also leads to much better performance on several games.


Earthquakes cause considerable economic losses. It is possible to minimize the economic loses by proper seismic design. In this paper basic principles for seismic design are summarized. There are three basic requirements to be satisfied; (a) strength, (b) ductility and (c) stiffness. In the paper these are briefly discussed. In the second part of the paper the author summarizes his views on the damages observed in the past earthquakes. He concludes that most of the damages have been due to, (a) bad configuration, (b) inadequate detailing and (c) inadequate supervision. In the paper these are discussed, pointing out the common mistakes made and damages observed as a result of these mistakes. In the last part of the paper some simple recommendations are made for producing seismic resistant reinforced concrete structures, emphasizing on detailing and proportioning.


of the Dissertation Optical Forces from Periodic Adiabatic Rapid Passage Sequences on Metastable Helium Atoms by Daniel Thomas Stack Doctor of Philosophy in Physics Stony Brook University 2012 Over the past 30 years, optical manipulation of neutral atoms has been primarily performed with a monochromatic laser beam. The simplest tool for the control of atomic motion is the radiative force exerted by a monochromatic laser on a twolevel atom. The radiative force arises from absorption followed by spontaneous emission, and its magnitude is limited by the atom's excited state lifetime. The coherent momentum exchanges between light fields and atoms can be exploited to produce long-range optical forces much greater than the radiative force through the use of absorption-stimulated emission processes. Adiabatic Rapid Passage (ARP) is a long-existing method to invert the population of a two-level nuclear spin system. Its extension to the optical domain iii necessitates a frequency chirped light pulse to interact with a two-level atom via the dipole interaction. I will first present a numerical study of the properties of optical forces on moving atoms derived from purely stimulated processes produced by multiple ARP sequences. This will be followed by experimental observations of long-range ARP forces much larger than the radiative force in metastable helium. Sequences of properly timed laser pulses may be used for rapid deceleration of neutral atomic (or molecular) beams.


Newly available lightweight cine camera equipment provided affluent British holiday-makers with an innovative travel accessory in the mid 1920s. Travel narratives produced by early camera-touting enthusiasts may be likened to preceding forms of travel experience depicted in art and written form, but important differences occur too. This discussion explores issues of place representation, ethnography and perceptions of regional identities, cultures, and histories through reference to amateur holiday footage filmed in the Balkans in 1934. Analysis of rural and urban scenes, traditions, and itinerary, as well as the cinematic processes found within this filmic travelogue, are related to earlier outsiders' responses and contemporary travel texts including guides, diaries and other genres of travel literature. Contemporary debates on post-conflict identity in the Balkan region and tourism history within the Mediterranean, as well as socio-cultural and aesthetic aspects of non-professional film making form a wider context for this focus upon Balkan imagery.


Purpose: The main objective of present research investigation is to formulate the sustained release formulation of Rosuvastatin. Rosuvastatin, an antihyperlipidemic agent, belongs BCS class-II agent.Methods: The SR tablets of Rosuvastatin were prepared employing different concentrations of HPMCK4M and SCMC in different combinations by Direct Compression using 32 factorial design. The concentration of Polymers , HPMCK4M and SCMC required to achieve the desired drug release was selected as independent variables, X1 and X2 respectively whereas, time required for 10% of drug dissolution (t10%), 50% (t50%), 75% (t75%) and  90% (t90%)  were selected as dependent variables.Results and Discussion: Totally nine formulations were designed and are evaluated for hardness, friability, thickness, % drug content, In-vitro drug release. From the Results it was concluded that all the formulation were found to be with in the Pharmacopoeial limits and  the In-vitro dissolution profiles of all formulations were fitted in to different Kinetic models, the statistical parameters like intercept, slope & regression coefficient  were calculated. Polynomial equations were developed for dependent variables. Validity of developed polynomial equations were verified by designing 2 check point formulations (C1, C2). According to SUPAC guidelines the formulation (F4) containing 30 mg of HPMCK4M and 40 mg of SCMC, is the most similar formulation (similarity factor f2= 89.561, dissimilarity factor f1= 1.543 & No significant difference, t= 0.0056) to marketed product (CRESTOR).Conclusion: The selected formulation (F4) follows Zero order, Higuchi's kinetics, and the mechanism of drug release was found to be Non-Fickian Diffusion (n= 0.963).


The concept of mediatization has proved remarkably popular in the past decade, although recent critiques have challenged its media-centrism, ahistoricism, and conceptual clarity. In this article, we draw on the work of those who suggest that mediatization is best deployed as a means of understanding particular social domains and the ways in which institutions and actors orientate their activities towards media. Using association football, or soccer, as our focus we offer a bottom-up perspective using data gathered from research workshops with young people in England. These not only demonstrate the extent to which football is followed through a range of media platforms but also how broader understandings of the game are shaped by these engagements. Moreover, we adapt insights from recent phenomenological approaches to media to focus on the practical, embodied forms of knowledge and habit that shape how football is currently played, followed, and debated.


Despite the advanced processing advantages for low cost, flexible and highly efficient solar cells, the technology is still facing the challenges with regard to the stability of materials in terms of moisture, thermal, light and oxygen atmosphere. The recent discovery of lead halide perovskite has increased a surge of interest in the field of photovoltaics. The chapter highlights some ways that can improve the stability and reducing the toxicity without compromising the efficiency of perovskite. Most of the part includes the review on the actual knowledge and cutting edge research results of high efficiency perovskites. It further describes the materials (Oxides and hybrid halides) that can be used for real time solar cell applications.


Firms using online advertising regularly run experiments with multiple versions of their ads since they are uncertain about which ones are most effective. Within a campaign, firms try to adapt to intermediate results of their tests, optimizing what they earn while learning about their ads. But how should they decide what percentage of impressions to allocate to each ad? This paper answers that question, resolving the well-known "learn-and-earn'' trade-off using multi-armed bandit (MAB) methods. The online advertiser's MAB problem, however, contains particular challenges, such as a hierarchical structure (ads within a website), attributes of actions (creative elements of an ad), and batched decisions (millions of impressions at a time), that are not fully accommodated by existing MAB methods. Our approach captures how the impact of observable ad attributes on ad effectiveness differs by website in unobserved ways, and our policy generates allocations of impressions that can be used in practice. We implemented this policy in a live field experiment delivering over 700 million ad impressions in an online display campaign with a large retail bank. Over the course of two months, our policy achieved an 8% improvement in the customer acquisition rate, relative to a control policy, without any additional costs to the bank. Beyond the actual experiment, we performed counterfactual simulations to evaluate a range of alternative model specifications and allocation rules in MAB policies. Finally, we show that customer acquisition would decrease about 10% if the firm were to optimize click through rates instead of conversion directly, a finding that has implications for understanding the marketing funnel.


We consider the relative complexities of a large number of computational geometry problems whose complexities are believed to be roughly (n4=3). For certain pairs of problems, we show that the complexity of one problem is asymptotically bounded by the complexity of the other. Almost all of the problems we consider can be solved in time O(n ) or better, and there are (n) lower bounds for a few of them in specialized models of computation. However, the best known lower bound in any general model of computation is only (n logn). The paper is naturally divided into two parts. In the rst part, we consider a large number of problems that are harder than Hopcroft's problem. These problems include various ray shooting problems, sorting line segments in IR, collision detection in IR, and halfspace emptiness checking in IR. In the second, we survey known reductions among problems involving lines in three-space, and among higher dimensional closestpair problems. Some of our results rely on the introduction of formal in nitesimals during reduction; we show that such a reduction is meaningful in the algebraic decision tree model.


Leverage your online influence with this fun and friendly guide to Klout!Klout measures your online influence on a scale of 1 to 100 by looking at your number of followers or connections, as well as by measuring your ability to drive action on social networks. This easy-to-understand guide helps you understand how Klout works so that you can use it to your advantage to leverage your online influence. You'll learn how to create a Klout profile and connect it to various social networks so that your data can be analyzed by Klout, determining your reach, amplification, and impact online. Shows you how to use Klout to spread your message and prioritize customersWalks you through setting up an account and creating your profile on KloutCovers the various facets of Klout and how to interpret Klout's data about you Highlights ways to understand Klout style and use Klout perks Klout For Dummies is essential reading if you're looking to increase your online clout!


The development of peer to peer overlay networks applications has attracted an immense interest from the research community in recent years. Several challenging issues have to be resolved in order to provide accessible, efficient and scalable inter-peer communication. Achieving resilience so as to reduce the disconnection probability, is among the most demanding issues to provide a robust and omnipresent service to peer to peer applications. This paper attempts to address this issue, by proposing a graph-theoretic model using the well-known star interconnection network with sub-logarithmic degree characteristics, which not only facilitate scalability problem, but also achieves maximum connectivity compared to the other existing graph-based methods. The simulation results confirm that the proposed solution attains a higher degree of resiliency compared to other existing topologies.


In applying Bayes's theorem to the history of science, Bayesians sometimes assume – often without argument – that they can safely ignore very implausible theories. This assumption is false, both in that it can seriously distort the history of science as well as the mathematics and the applicability of Bayes's theorem. There are intuitively very plausible counter-examples. In fact, one can ignore very implausible or unknown theories only if at least one of two conditions is satisfied: (i) one is certain that there are no unknown theories which explain the phenomenon in question, or (ii) the likelihood of at least one of the known theories used in the calculation of the posterior is reasonably large. Often in the history of science, a very surprising phenomenon is observed, and neither of these criteria is satisfied.


Smoking cessation interventions in the UK are being developed in the context of widening socio-economic differentials in both prevalence and cessation. These differ entials are evident among pregnant women, the group targeted for interventions directed at women. Recent research has suggested that, among the disadvantages associated with low socio-economic status, being dependent on means-tested benefits may be a particularly powerful influence on snuokimg status and a major barrier to quitting. Intervention programmes have been heavily influenced by the transtheoretical model, which maps the quitting process as a patterned sequeuce of 'stages of change'. However, little is known about the stage-of-change profile in the UK population or about the socio- economic patterning of the profile. This paper begins to fill these gaps in the knowledge base of health promotion with respect to women in pregnancy. It reports on a survey of 2000 expectant mothers conducted in 1996 in the West Midlands. First pregnancy was found to have an intervention-like effect, with a high proportion of first-time expectant mothers who entered pregnancy as smokers either planning to quit or having done so. This intervention-like effect was moderated by women's socio-economic circumstances. Being in receipt of means-tested benefits increased the odds of a woman not intending to give up smoking in the foreseeable future.


In 2016, electric car manufacturer Tesla announced that it was making an offer to acquire solar panel manufacturer SolarCity in an all-stock offer worth $2.6 billion in Tesla stock. Tesla's co-founder and CEO, Elon Musk, believed that the merger would generate significant cost and revenue synergies, based on his vision of the future of transportation, energy storage, and a "green" economy. However, most Wall Street analysts were highly skeptical of the deal, voicing concerns that the merger would burden Tesla with excessive debt and that Musk was using the deal to advance his personal interests (at the expense of public shareholders) and bail out Tesla. Concerns were raised over possible conflicts of interest, given that Musk owned over 20% of the stock, and sat on the board of directors of both companies. The viability of the merger was also questioned given that neither Tesla nor SolarCity had ever been profitable.


Pratylenchus thornei and P. neglectus are two species of root-lesion nematode that cause substantial yield losses in wheat. No commercially available wheat variety has resistance to both species. A doubled-haploid population developed from a cross between the synthetic hexaploid wheat line CPI133872 and the bread wheat Janz was used to locate and tag quantitative trait loci (QTLs) associated with resistance to both P. thornei and P. neglectus. Wheat plants were inoculated with both species of nematode in independent replicated glasshouse trials repeated over 2 years. Known locations of wheat microsatellite markers were used to construct a framework map. After an initial single-marker analysis to detect marker-trait linkages, chromosome regions associated with putative QTLs were targetted with microsatellite markers to increase map density in the chromosome regions of interest. In total, 148 wheat microsatellite markers and 21 amplified fragment length polymorphism markers were mapped. The codominant microsatellite marker Xbarc183 on the distal end of chromosome 6DS was allelic for resistance to both P. thornei and P. neglectus. The QTL were designated QRlnt.lrc-6D.1 and QRlnn.lrc-6D.1, for the 2 traits, respectively. The allele inherited from CPI133872 explained 22.0-24.2% of the phenotypic variation for P. thornei resistance, and the allele inherited from Janz accounted for 11.3-14.0% of the phenotypic variation for P. neglectus resistance. Composite interval mapping identified markers that flank a second major QTL on chromosome 6DL (QRlnt.lrc-6D.2) that explained 8.3-13.4% of the phenotypic variation for P. thornei resistance. An additional major QTL associated with P. neglectus resistance was detected on chromosome 4DS (QRlnn.lrc-4D.1) and explained a further 10.3-15.4% of the phenotypic variation. The identification and tagging of nematode resistance genes with molecular markers will allow appropriate allele combinations to be selected, which will aid the successful breeding of wheat with dual nematode resistance.


Many neural circuits are capable of generating multiple stereotyped outputs after different sensory inputs or neuromodulation. We have previously identified the central pattern generator (CPG) for Xenopus tadpole swimming that involves antiphase oscillations of activity between the left and right sides. Here we analyze the cellular basis for spontaneous left–right motor synchrony characterized by simultaneous bursting on both sides at twice the swimming frequency. Spontaneous synchrony bouts are rare in most tadpoles, and they instantly emerge from and switch back to swimming, most frequently within the first second after skin stimulation. Analyses show that only neurons that are active during swimming fire action potentials in synchrony, suggesting both output patterns derive from the same neural circuit. The firing of excitatory descending interneurons (dINs) leads that of other types of neurons in synchrony as it does in swimming. During synchrony, the time window between phasic excitation and inhibition is 7.9 ± 1 ms, shorter than that in swimming (41 ± 2.3 ms). The occasional, extra midcycle firing of dINs during swimming may initiate synchrony, and mismatches of timing in the left and right activity can switch synchrony back to swimming. Computer modeling supports these findings by showing that the same neural network, in which reciprocal inhibition mediates rebound firing, can generate both swimming and synchrony without circuit reconfiguration. Modeling also shows that lengthening the time window between phasic excitation and inhibition by increasing dIN synaptic/conduction delay can improve the stability of synchrony.


Sultan Abdülaziz Imperial Hunting Lodge was built in the second half of 19 th century during the construction of the Anatolian-Balkan Railway, which played an important role in the urban development of Izmit. This imperial lodge outside the capital city might have been constructed on the foundations of a former palace built during the reign of Murat IV. Due to its location above the Izmit Gulf, it has become one of the most important elements of the urbanscape. Witnessing important turning points in the history of the city, the lodge has been used as the centre of local government and then as a museum. It has been affected by a number of major earthquakes due to its location on the North Anatolian Fault, and following its latest restoration in 1998, it suffered great damage during the Kocaeli earthquake of August 17, 1999. The damage was further aggravated as the building had not been well maintained, had been the subject of inappropriate repair interventions and left exposed to the effects of climatic conditions. The most important type of damage observed in the building was structural deformations of various types: the walls drifted outwards at the roof level while vertical detachments and cracks of various shapes and sizes were observed along the walls and the roof parapet walls were separated at the corners as a result of the earthquake. In order to decide on the type, method and techniques of intervention necessary, the architectural, structural and material characteristics of the building as well as the level of damage had to be studied and documented in detail. This data was then evaluated with the contribution of specialists in various fields and conservation, restoration and structural strengthening methodologies were developed. The intervention aimed at re-using the original building material detached during the earthquake while the basic principles were defined as an accurate analysis of the types of damage and the implementation of the solutions to these problems by the use of original materials and construction techniques through minimal intervention.


In the field of image processing and recognition, discrete cosine transform (DCT) and principal component analysis (PCA) are two widely used techniques. In this paper we present a face recognition approach based on them. Feature selection (FS) is a global optimization problem in machine learning, which reduces the number of features, removes irrelevant, noisy and redundant data, and results in acceptable recognition accuracy. It is the most important step that affects the performance of a face recognition system. Genetic Algorithms (GA), one of the most recent techniques in the field of feature selection, are a type of evolutionary algorithms that can be used also to solve this issue. The application of a GA in the resolution of a problem requires the coding of the potential solutions to this problem in finite bit chains in order to constitute the chromosomes coming from a population formed by candidate points. The aim is to find a selective function allowing good discrimination between chromosomes and to define the genetic operators that will be used. In this sense, this approach seeks to develop a system of face recognition using Genetic Algorithm and a DCT-PCA combination for feature selection and dimensionality reduction, to be applied to an archive of images of human faces. The proposed approach is applied on various Face Databases. Experimental results demonstrate the effectiveness of this approach compared to state of the art in face recognition.


Dr. Douglas Hodgins firstname.lastname@example.com Background Calves are born before their immune systems are fully developed. A newborn calf relies on maternal antibodies from the dam's colostrum for disease protection (passive immunity) until the calf's immune system (active immunity) becomes fully functional. The transition between passive and active immunity occurs at approximately 6 weeks of age. If calves could be vaccinated effectively in the first weeks of l ife, antibodies produced by the calf active immune system would take over to protect the calf as protection from the maternal antibodies in the colostrum decreases. So far, early calfhood vaccination has not been very effective for two reasons. First , the calf's immune system is immature. Second, the active immune cells that the calf does produce are inhibited by maternal antibodies. A better understanding of the neonatal immune system may help develop vaccines that are more effective in newborn calves. B lymphocytes (B cells) are white blood cells that play an important front-line role in the active immune response. B cells detect and respond to foreign cells like disease organisms. This project studied two receptors on the surface of B cells. These receptors are called CD21 and CD32, and they can have opposite effects on the calf's active immune response. The CD21 receptor binds a protein called C3d, which is also produced by the active immune system. If the C3d is bound to an antigen from a foreign cell , the B cell is alerted that a foreign cell has been detected, and the immune response is massively amplified to attack those foreign cells. C3d is found in high concentrations in adult cattle, but in low levels in newborn calves. As a result , adding C3d to vaccines for young calves may help activate B cells and enhance antibody responses. However, the CD32 receptor binds maternal antibodies. If the maternal antibody is bound to an antigen, the active immune response through the CD21 receptor is inhibited. The expression of CD21 (which activates the active immune response) and CD32 (which inhibits the active immune response) by B cells from neonatal calves needed to be evaluated before vaccine trials were pursued further. Objectives To characterize the activating and inhibitory receptors on B lymphocytes and conduct experiments to better understand how complement component C3d might be used to develop effective calfhood vaccines. This builds on earlier research funded by the BCRC. What they did The researchers examined B cells from calves up to 6 months of age. Two alternative forms of the CD32 receptor were detected which had never been found in cattle before. A highly sensitive technique was developed to distinguish expression of the various forms of CD32 in the B cells of newborn calves. Pilot experiments were carried out to assess the reactivity and effectiveness of C3d as a vaccine component. What they learned Even at birth, 90% or more of blood B cells expressed both CD21 (activating) and CD32 (inhibitory) receptors. However, the number of B cells in blood was less than 20% of that in adults, and the intensity of CD21 and CD32 receptor expression was lower in calves than in adults. The CD32 receptors reached adult levels in only three weeks, while the CD21 receptors reached adult levels at 6 weeks of age. The greater inhibitory action of CD32 receptors versus the activating action of CD21 receptors at 3 weeks of age is likely part of the challenge in developing an effective vaccinate for newborn calves. To make things even more complicated, the two distinct forms of the CD32 receptor discovered in this study also appear to inhibit active immune responses by two different mechanisms in newborn calves. Vaccines with different formulations of C3d and containing a model antigen were developed and administered to 14-day and 6-month-old calves to assess local reactions at the injection si tes and their abil i t ies to increase antibody responses. No symptoms of toxicity were observed. However, adding C3d did not strengthen the immune response, either. More work is underway to develop alternative strategies to improve C3d formulation and improve the effectiveness of the experimental vaccine. What it means This research was conducted to learn more about the complex changes the immune system undergoes during the transit ion between passive and active immunity in young calves. This research has not yet developed an improved vaccine. However, this new knowledge about the immune system's activating and inhibitory signals will help in future efforts to develop more effective vaccines for use in newborn calves.


We present a conception that surmounts the Cartesian Cut -prevailing in science- based on a representation of the fusion of the physical 'objective' and the 'subjective' realms. We introduce a mathematical-physics and philosophical theory for the physical realm and its mapping to the cognitive and perceptual realms and a philosophical reflection on the bearings of this fusion in cosmology, cognitive sciences, human and natural systems and its relations with a time operator and the existence of time cycles in Nature's and human systems. This conception stems from the self-referential construction of spacetime through torsion fields and its singularities; in particular the photon's self-referential character, basic to the embodiment of cognition ; we shall elaborate this in detail in perception and neurology. We discuss the relations between this embodiment, bio-photons and wave genetics, and the relation with the enactive approach in cognitive sciences due to Varela. We further discuss the relation of the present conception with Penrose's theory of consciousness related to non-computatibility -in the sense of the Goedel-Turing thesis- of quantum processes in the brain.


Maximal overlap discrete wavelet transform is used to perform spectral analysis of geomagnetic storm sudden commencements (SCs) (SSCs). This spectral analysis guided us in the development of an automatic SSC detection algorithm. The SC can be an indicator of the onset of a geomagnetic storm; in this case, it is called an SSC. The geomagnetic records used in this study were 3-s resolution data collected from the Circum-Pan Pacific Magnetometer Network. Using such high-resolution data enabled us to achieve a small detection error and short processing time. In addition to these technical merits, we introduce a new algorithm that automatically detects, for the first time, the SC from high-resolution data (sampled at the rate of 1 sample/3 s), unlike previous studies that focused on determining the SSC times automatically using 1-min data. Ninety-three geomagnetic storms were considered for testing the proposed algorithm; it was found that the average and maximum standard deviation of the errors in the detection times determined by the algorithm were 7 and 18 samples, respectively, of the corresponding manually determined arrival times.


Small ruminants, which account for more than half of the domesticated ruminants in the world, are an important component of the farming systems in most developing countries. Despite their economic and social importance, socio-economic and marketing research on small ruminants has so far been limited, a fact which also holds strongly true in Ethiopia. This study, based on survey data of 5004 Ethiopian smallholder households, uses analysis of descriptive information and econometric analysis to draw implications to promote market orientation. Econometric results are based on estimation of bivariate, ordinal, and multinomial probit models. We find that small ruminant herd size, large ruminant herd size, herd structure, access to livestock market, and involvement in the institutional services of extension and credit stand out as important factors affecting market participation behavior of households. We find optimal herd size of 41 heads of animals after which probability of participation as seller declines and an optimal herd size of 21 heads of animals after which probability of participation as buyer declines. Our results imply that an effective package of interventions to promote market oriented small ruminant production will need to include development of livestock market infrastructure and market institutions, improved access to extension and credit use, efficient animal reproduction and management, and proper animal health care.


Clinical management of patients with symptoms caused by pharmacological refractory hypertrophic obstructive cardiomyopathy must consider surgical myectomy, percutaneous transluminal septal myocardial ablation and implantation of a DDD pacemaker. Until now, no prospective, double blind, randomized studies have yet been carried out to determine the merits of each of these treatment alternatives. However, uncontrolled studies have shown that short atrioventricular delay dual-chamber pacing reduces outflow tract obstruction. Aim of the study was to investigate the results of the pacemaker therapy in a prospective, double blind randomized crossover procedure. All patients with hypertrophic obstructive cardiomyopathy included in this multicenter study were either refractory or intolerant to drugs and typically had pressure gradients higher than 30 mm Hg. In 83 patients, mean age 53 (18 to 82) years who responded favorably to a temporary pacing test, a DDD pacemaker was implanted. After echo- and echo-Doppler-based measurements of hemodynamic parameters the patients were randomized into 2 groups, those with an implanted pacemaker in the inactivated mode (AAI) and those with a pacemaker in the activated mode (DDD with optimized short AV delay). A crossover of these groups was performed after 12 and 24 weeks, respectively. Both objective parameters of echo including Doppler, and spiroergometry, and subjective parameters of angina, dyspnea, and quality of life were recorded. Additionally, subgroups based on age decades were analyzed. After 12 weeks in the DDD mode, regardless of the randomization sequence, a decrease of the pressure gradient from 59 +/- 36 mm Hg (median) to 30 +/- 25 mm Hg was proven significant (p < 0.001). The endurance of the patients who, during screening, achieved less than 10 minutes of exercise by the Bruce protocol improved by 21% under DDD mode. The main symptoms, as measured by the NYHA classification, improved statistically significant from a mean of 2.4 to 1.7 for functional class, from a mean of 2.4 to 1.4 for dyspnea and from a mean of 1.0 to 0.4 for angina. Subgroup analysis showed improvements depended significantly upon age, with a marked improvement between the ages of 60 and 70, which was statistically significant as compared to other decades. Subjective improvements in the quality-of-life of patients was measured using a specially developed questionnaire. These findings justify, by all means, the intention to implant a DDD pacemaker in older patients. In younger and/or such patients with elevated pressure gradients, the results of ongoing randomized studies comparing myectomy, PTSMA and pacing have to be considered.


Title of Document: ESSENTIALLY POWERFUL: POLITICAL MOTHERHOOD IN THE UNITED STATES AND ARGENTINA Meghan K. Gibbons, Doctor of Philosophy, 2007 Directed By: Professor Phyllis A. Peres, Professor, School of Languages and Linguistics "Essentially Powerful" explores the roles of essentialism around motherhood in the political protests of two groups in the United States and Argentina. Another Mother for Peace in the U.S. and the Madres de la Plaza de Mayo in Argentina based their protests on their identities as mothers, authorizing themselves to challenge their states' actions around their children. The states themselves also used the figure of the mother to promote specific behaviors that limited political opposition. The contrast between these two approaches problematizes the figure of the subject within poststructuralist and feminist debates about resistance. The subject is seen alternately as an active agent who can use essentialism strategically and a discursive construction that can be easily manipulated by ideology. This study explores the ground between these two poles, mapping the ways in which essentialisms around motherhood can be proscriptive in the hands of hegemons, but empowering when used by subjects themselves, who blend experience with essence. Interviews with participants in both groups as well as testimonial accounts, films and media coverage of the groups combine to allow a rich exploration of essentialisms by the mothers and their states. My first chapter explores how the Madres and the dictatorship used essentialism to struggle for discursive control over Argentine motherhood. The Madres' authorization of themselves as public, political subjects –in interviews, testimonies and letters-challenged the dictatorship's formation of motherhood as a private, domestic identity. Chapter two examines the representation of the Madres' protests in film, exploring the ambivalence that Argentine audiences experienced in the women's blurring of several traditional binaries: emotion and reason, family and state, private and public. My third and fourth chapters analyze the narrative strategies of Another Mother for Peace. These North American mothers used essentialism to justify their movement into the public, political sphere, while still performing traditional, domestic motherhood in strategic ways. My final section explores how distinct cultural, religious and historical paradigms inflected the experiences of these two mothers' groups differently, facilitating and/or problematizing their uses of essentialist identities. This analysis critiques the limitations of both proscriptive and biological essentialisms, and allows us to see how the mothers' own experiences of motherhood pushed them beyond the boundaries of traditional essentialism and into new subjectivities. ESSENTIALLY POWERFUL: POLITICAL MOTHERHOOD IN THE UNITED STATES AND ARGENTINA


There are many kinds of printed dot matrix fonts. They mainly differ in characters' structure since some of them are built with touching dots and some not. Two more variations an efficient character segmentation method has to cope with are fonts printed in italic and illumination changes depending on the environmental conditions. Hence, a procedure is introduced that uses the projection profile of the mean of several least gray values to estimate the skew angle of text lines and the characters' slant angle. Furthermore, based on the projection profile the decision boundaries for line and character segmentation are estimated with a least squares estimator. This has the advantage that the boundaries are adapted for every image. Finally, skew and slant angles are corrected and the characters are segmented. The robustness and accuracy is shown in experiments on data captured with an industrial camera.


STUDY OBJECTIVES
Sleep after learning often benefits memory consolidation, but the underlying mechanisms remain unclear. In previous studies, we found that learning a visuomotor task is followed by an increase in sleep slow wave activity (SWA, the electroencephalographic [EEG] power density between 0.5 and 4.5 Hz during non-rapid eye movement sleep) over the right parietal cortex. The SWA increase correlates with the postsleep improvement in visuomotor performance, suggesting that SWA may be causally responsible for the consolidation of visuomotor learning. Here, we tested this hypothesis by studying the effects of slow wave deprivation (SWD).

DESIGN
After learning the task, subjects went to sleep, and acoustic stimuli were timed either to suppress slow waves (SWD) or to interfere as little as possible with spontaneous slow waves (control acoustic stimulation, CAS).

SETTING
Sound-attenuated research room.

PARTICIPANTS
Healthy subjects (mean age 24.6 +/- 1.0 years; n = 9 for EEG analysis, n = 12 for behavior analysis; 3 women).

MEASUREMENTS AND RESULTS
Sleep time and efficiency were not affected, whereas SWA and the number of slow waves decreased in SWD relative to CAS. Relative to the night before, visuomotor performance significantly improved in the CAS condition (+5.93% +/- 0.88%) but not in the SWD condition (-0.77% +/- 1.16%), and the direct CAS vs SWD comparison showed a significant difference (P = 0.0007, n = 12, paired t test). Changes in visuomotor performance after SWD were correlated with SWA changes over right parietal cortex but not with the number of arousals identified using clinically established criteria, nor with any sign of "EEG lightening" identified using a novel automatic method based on event-related spectral perturbation analysis.

CONCLUSION
These results support a causal role for sleep slow waves in sleep-dependent improvement of visuomotor performance.


Policy of Multi-Actor Systems is an introduction into the art of craft of problem exploration and problem structuring. It positions policy analysis as a scientific discipline focused on systems analysis in a multi-actor context to support better informed decision-making.
The approach presented in this book is considered to be the cornerstone of the curricula of the Faculty of Technology, Policy and Management of Delft University of Technology and underlies the research on (the governance of) socio-technical systems. Systems thinking applied in a multi-actor environment and its inherent multi-disciplinary character is what makes this work stand out from traditional hard- and soft systems approaches.
The core of the book is dedicated to systems analysis, actor- or stakeholder-analysis and discusses methods for dealing with uncertainty. These analytical activities combined lead to a rich problem description and to plans for further research. Due to the stepwise approach this book serves as a basis for any problem analysis both for our bachelor and master students, our alumni worldwide and any interested practitioners.


Evaluation of different antimicrobial activity against Streptococcus pneumoniae from adults with community-acquired pneumonia Steptococcus pneumoniae is the main etiologic bacterial agent of respiratory tract infections and in recent years emergence of isolates with multiple resistance has been observed. During the years 2008 and 2009 we studied 59 S. pneumoniae strains isolated from blood cultures and respiratory materials from patients with pneumonia and tested their susceptibility to different antimicrobials. There was no resistance to parenteral penicillin (intravenous), amoxicillin, ceftriaxone and carbapenems. To oral and parenteral cefuroxime the resistance was 3.4% and 5.1% respectively; 15.2% of the isolates showed intermediate susceptibility to oral penicillin with MICs between 0.125 and 1 μg/ml. Only 1/59 isolates Correspondencia Beatriz Weyland Domicilio Postal: Córdoba 2351 Hospital de Clínicas "José de San Martín" Departamento de Bioquímica Clínica. C.A.B.A Correo electrónico: firstname.lastname@example.com Teléfono: 5950-8691/8692/8696 Recibido: 18.01.2011 Aceptado: 12.07.2011 Revista Americana de Medicina Respiratoria Vol 11 No 3 Septiembre 2011 118 was resistant to levofloxacin (MIC = 8 μg/ml) but it was susceptible to gatifloxacin (MIC = 0.5 μg/ml). Erythromycin resistance was 20.3% and the predominant phenotype was M (efflux) confirmed by the presence of the mef gene. Tetracycline resistance was 6.8% and there was no resistance to tigecycline (CIM90 = 0.5 μg/ml). All isolates were susceptible to vancomycin, linezolid and rifampicin. The resistance to trimethoprim-sulfamethoxazole was 21.4%. In conclusion, parenteral (intravenous) penicillin and amoxicillin, independently of the way of administration, remain the antimicrobial β-lactams most suitable for the empirical treatment of pneumonia, while macrolides should be used with caution because of the high proportion of resistance. Although levofloxacin resistance remains low, we consider it should only be used in special situations and in adequate doses in order to prevent the selection of resistant mutants.


Internal undular bores have been observed in many parts of the world. Studies have shown that many marine structures face danger and risk of destruction caused by internal undular bores due to the amount of energy it carries. This paper looks at the transformation of internal undular bore in two-layer fluid flow under the influence of variable topography. Thus, the surface of the bottom is considered to be slowly varying. The appropriate mathematical model is the variable-coefficient extended Korteweg-de Vries equation. We are particularly interested in looking at the transformation of KdV-type and table-top undular bore over the variable topography region. The governing equation is solved numerically using the method of lines, where the spatial derivatives are first discretised using finite difference approximation so that the partial differential equation becomes a system of ordinary differential equations which is then solved by 4 th order Runge-Kutta method. Our numerical results show that the evolution of internal undular bore over different types of varying depths regions leads to a number of adiabatic and non-adiabatic effects. When the depth decreases slowly, a solitary wavetrain is observed at the front of the transformed internal undular bore. On the other hand, when the depth increases slowly, we observe the generation of step-like wave and weakly nonlinear trailing wavetrain, the occurrence of multi-phase behaviour, the generation of transformed undular bore of negative polarity and diminishing transformed undular bore depending on the nature of the topography after the variable topography.


Background:Congenital heart diseases (CHD) are lesions caused by abnormal development of the structure of the heart.heart failure(HF) is a common complication of CHD.Elevated Fibroblast growth factor 23 (FGF-23) levels were associated with increased risk of cardiovascular diseases (CVD) and mortality in general population. Aim of the study: The aim of this study wasto assess serum FGF-23 levels among pediatric heart failure patients to demonstrate relationship between its levels and cardiac function and severity of the disease. Patients and methods: In our study we have evaluated 60 children. They were divided into two groups: A case group: Included 30 patient with HF secondary to CHD and A control group: Included 30 age and sex matched apparently healthy children.The diagnosis of cases was established from the history, clinical examination investigation. All patients were subjected to full history taking, a complete clinical examination including Ross Score for detection of the degree of heart failure, Complete blood count ,kidney function tests, chest X ray, ECHO was performed and serum level of FGF-23was also measured. Results:There were statistical significant decrease in Ejection fraction (EF) and Fractional Shortening (FS) of HF group compared to control group. There was significant increase in LVEDD, LVESD and ESPAP in HF group compared to control group. There was a statistical significant increase in serum FGF-23 level in HF group compared to healthy one. According to correlation analysis there was significant positive correlation between FGF-23 and Heart rate, respiratory rate, HB and Modified Ross score, also there was significant negative correlation between FGF-23 and FS, EF, while there was no significant correlation between FGF-23 and age, ESPAP, phosphorous and creatinine. The best cut-off value for FGF-23in HF patients was 141.5 ng/dl with sensitivity 88.3%, specificity 89.7%, positive predictive value 80.2%, negative predictive value 91.5%, accuracy 88% and area under curve 0.982. So, FGF-23 can be a good sensitive and specific marker for HF. Conclusion:This study demonstrated that FGF23 is diagnostic for heart failure with good sensitivity and specificity and related to severity of heart failure and correlate significantly with left ventricular function.


Ecological risk assessments of chemicals can be informed by a suite of effect models, including population and food web models. In the risk assessments conducted under EU regulation 793/93/EC, however, applications of such effect models are extremely scarce and toxicity‐extrapolation approaches are often used instead. The objective of the present study was to re‐evaluate these risk assessments using two types of effect models: species sensitivity distributions (SSDs, non‐mechanistic), and food web models (mechanistic). Species sensitivity distributions significantly fitted the available toxicity data for up to 35% of the chemicals, depending on the trophic levels included and the amount of data available. Median hazardous concentrations for 5% of the species (HC5‐50) estimated by the SSDs were less accurate predictors of measured community‐level no observed effect concentration than food web model‐derived HC5‐50s, albeit data were available for seven chemicals only. For datasets with more than 10 data points, the 90% confidence interval of the estimated HC5s was narrower for the food web modeling approach than for the SSD approach. The HC5‐50s predicted by the two approaches were two to five times (metals) and 10 to 100 times (organic chemicals) higher than the predicted no effect concentrations (PNECs) for the aquatic environment listed in the risk assessment reports. This suggests that the derived PNECs are protective for aquatic ecosystems. Environ. Toxicol. Chem. 2013;32:594–601. © 2012 SETAC


This research employs the Data Envelopment Analysis (DEA) and Malmquist index approaches to evaluate the efficiency and Total Factor Productivity (TFP) changes of Thai banking system in the period of 2007-2010 using panel data of 27 major banks in Thailand. This paper shows that the global crisis had a late effect on Thai banks as the TFP only dropped in 2010. While the local banks maintained their stable, foreign banks were more fluctuating – some improved their TFPs, some did not and become worst performers in the system. The reason behind it may relate to the fact that Thai banking system is currently running at decreasing returns to scale situation, which proposes that Thai banks are wasting resources in over-expansion. Hence, continuing to develop and restructuring the banking system is an emergence task for Thailand in the near future.


History must be detached from the image that satisfied it for so long, and through which it found its anthropological justification: that of an age-old collective consciousness that made use of material documents to refresh its memory; history is the work expended on material documentation (books, texts, accounts, registers, acts, buildings, institutions, laws, techniques, objects, customs, etc.) that exists, in every time and place, in every society, either in a spontaneous or in a consciously organized form. The document is not the fortunate tool of a history that is primarily and fundamentally memory; history is one way in which a society recognizes and develops a mass of documentation with which it is inextricably linked. Michel Foucault, The Archaeology of Knowledge


The reproductive biology of albacore tuna, Thunnus alalunga, in the western Indian Ocean was examined through analysis of the sex ratio, spawning season, length-at-maturity (L50), spawning frequency and fecundity. From 2013 to 2015, a total of 923 female and 867 male albacore were sampled. A bias in sex ratio was found in favor of females with fork length (LF) < 100 cm. Using histological analyses and gonadosomatic index, spawning was found to occur between 10°S and 30°S, mainly to the east of Madagascar from October to January. Large females contributed more to reproduction through their longer spawning period compared to small individuals. The L50 (mean ± standard error) of female albacore was estimated at 85.3 ± 0.7 cm LF. Albacore spawn on average every 2.2 days within the spawning region and spawning months, from November to January. Batch fecundity ranged between 0.26 and 2.09 million oocytes and the relative batch fecundity (mean ± standard deviation) was estimated at 53.4 ± 23.2 oocytes g-1 of somatic-gutted weight. The study provides new information on the reproductive development and classification of albacore in the western Indian Ocean. The reproductive parameters will reduce uncertainty in current stock assessment models which will eventually assist the fishery to be sustainable for future generations.


This article reports the results of a replication of Brooks and Manza's "Social Policy Responsiveness in Developed Democracies" published in 2006 in the American Sociological Review. The article finds that Brooks and Manza utilized an interaction term but excluded the main effect of one of the interacted variables. This model specification has specific implications: statistically, that the omitted main effect variable has no correlation with the residual error term from their regression; theoretically speaking, this means that all unobserved historical, cultural, and other characteristics that distinguish liberal democratic welfare regimes from others can be accounted for with a handful of quantitative measures. Using replicated data, this article finds that the Brooks and Manza models fail these assumptions. A sensitivity analysis using more than 800 regressions with different configurations of variables confirms this. In 99.5 percent of the cases, addition of the main effect removes Brooks and Manza's empirical findings completely. A theoretical discussion illuminates why these findings are not surprising. This article provides a reminder that models and theories are coterminous, each implied by the other.


This paper reports on a psycholinguistic experiment investigating information used in incremental interpretation to assign grammatical roles to case-marked nouns. The three core grammatical cases in Estonian – nominative, partitive and genitive – are syntactically ambiguous, in that they may function in various grammatical roles depending on the context. Our study probed what grammatical functions Estonian speakers assign to nouns marked in these cases prior to any knowledge of the syntactic structure of the clause. We investigated the effect of animacy and number, in combination with case-marking, on grammatical role assignment of clause-initial nouns. Results show that these cases are underspecified, and that the interpretation of nouns, when presented without prior context, involves semantic cues like animacy and number, which interact with morphological case to guide the assignment of grammatical functions.


Driven by the recent detection of an unidentified emission line previously reported at 3.55-3.57 keV in a stacked spectrum of galaxy clusters, in this work we investigated the resonant dielectronic recombination (DR) process in Li-like Ar as a possible source of, or contributor to, the emission line. The Li-like transition 1s22l-1s2l3l' was suggested to produce a 3.62 keV photon [1] near the unidentified line at 3.57 keV and was the primary focus of our study. The Electron Beam Ion Trap at NIST was used to produce and trap the highly-charged ions of argon. The energy of the quasi-monoenergetic electron beam was incremented in steps of 15 eV to scan over all of the Li-like Ar DR resonances. A Johann-type crystal spectrometer and a solid-state germanium detector were used to take x-ray measurements perpendicular to the electron beam. Our broadband results allowed us to identify the processes that produced specific spectral features, while our high-resolution spectra allowed the experimental separation of features that are less than 2 eV apart. We have used the collisional radiative model NOMAD [2] aided by atomic data calculations by FAC [3] to interpret our observations and account for corrections. Experimental results were compared to the atomic database AtomDB, used to fit the galaxy cluster spectra. We found a number of measured features due to DR in lower charge state Ar ions not included in the database, close in energy to the identified line at 3.57 keV, and suggest their inclusion for improved interpretation and diagnosis of other astrophysical spectra.


The Mars Sample Return mission has the goal to drill, break off, and retain rock core samples. After some results gained from rock core mechanics testing, the realization that scoring teeth would cleanly break off the core after only a few millimeters of penetration, and noting that rocks are weak in tension, the idea was developed to use symmetric wedging teeth in compression to weaken and then break the core at the contact plane. This concept was developed as a response to the break-off and retention requirements. The wedges wrap around the estimated average diameter of the core to get as many contact locations as possible, and are then pushed inward, radially, through the core towards one another. This starts a crack and begins to apply opposing forces inside the core to propagate the crack across the plane of contact. The advantage is in the simplicity. Only two teeth are needed to break five varieties of Mars-like rock cores with limited penetration and reasonable forces. Its major advantage is that it does not require any length of rock to be attached to the parent in order to break the core at the desired location. Test data shows that some rocks break off on their own into segments or break off into discs. This idea would grab and retain a disc, push some discs upward and others out, or grab a segment, break it at the contact plane, and retain the portion inside of the device. It also does this with few moving parts in a simple, space-efficient design. This discovery could be implemented into a coring drill bit to precisely break off and retain any size rock core.


Real-time performance monitoring to identify poorly or under-performing loops has become an integral part of preventative maintenance. Among others, rising energy costs and increasing demand for improved product quality are driving forces. Automatic process control solutions that incorporate real-time monitoring and performance analysis are fulfilling this market need. While many software solutions display performance metrics, however, it is important to understand the purpose and limitations of the various performance assessment techniques since each metric signifies very specific information about the nature of the process. This paper reviews performance measures from simple statistics to complicated modelbased performance criteria. By understanding the underlying concepts of the various techniques, readers will gain an understanding of the proper use of performance criteria. Basic algorithms for computing performance measures are presented using example data sets. An evaluation of techniques with tips and suggestions provides readers with guidance for interpreting the results.


BACKGROUND
Just as developing states are blessed with natural resources capable of transforming their economies into a positive direction, the imposed World Trade Organisation's (WTO) mores continue to relegate them to the status of underdevelopment. The consequences of this on investment, trade and finance in Third World States (TWSs), especially Africa, are disarticulation of the economy, exploitation, disinvestment, unemployment, political instability and unavailability of relevant technology to move TWSs forward, among others. This gives rise to the politics behind Rooibos (Aspalathus linearis) patenting (a medicinal plant found only in South Africa) by various multinational corporations (MNCs).

MATERIALS AND METHODS
This study adopted political economy approach with emphasis on both primary and secondary sources of data collection using content analysis.

RESULT
There is need to adhere strictly to the issues of intellectual property rights (IPRs), geographical indications (GIs), prior informed consent (PIC), and access and sharing benefits (ASB). These have not been observed by the western states because of their economic of neo-imperialism to the disadvantage of developing states.

CONCLUSION
This paper recommends that there is need for a regional regime such as African Regional Intellectual Property Organisation (ARIPO), on indigenous knowledge (IK) to patent the continental biodiversity resources.


There are two aims of this editorial article. The first is to present the current state of research related to widely defined Information Technology (IT) and Information Systems (IS) in the Visegrad Group (V4) of countries. The second is to introduce articles included in the special issue. While there are already reviews focused on the transition economies (Roztocki & Weistroffer, 2015), there is a lack of reviews which cover the four Visegrad Group countries—the Czech Republic, Hungary, Poland, and Slovakia. All four countries share similarities, such as recent historical events; they joined the European Union (EU) in 2014 and NATO in 1999 (with exception of Slovakia which joined in 2004)—thus 2014, when this issue was completed, was a year full of anniversaries—10 years since joining the EU, 15 years since joining NATO (10 years for Slovakia); also it was the 25th anniversary of the first free 1989 elections in Poland. However, it is important to stress that there are also socio-economic and political differences between the V4 countries. The transformation process from the centrally planned economy to the free market, from communism to democracy, was not easy and smooth and was full of mistakes, problems, and delays; nevertheless, it is a remarkable achievement. Lessons learned from the transformation, including the role of technology in the creation of the modern economy, and relevant societal changes, should be collected and analyzed to be applied in different contexts. This is especially important when failed attempts of the transition and modernization processes in the Middle East, or some post-communist countries, such as Ukraine have been witnessed. This is also an important issue from the academic point of view, as, unfortunately, such lessons are neither widely captured, nor available internationally; Roztocki and Weistroffer (2015) pointed out that research focused on transition economies is very limited. There are some changes in this trend, following publications of special issues on the topic, edited by Roztocki and Weistroffer (2008a, 2008b, 2011a, 2011b); however, such publications were focused on all transitional economies. This special issue is likely to be the first one covering solely the Visegrad Group of countries—the Czech Republic, Hungary, Poland, and Slovakia.
This editorial article is structured as follows. First some main terms are defined; this is followed by a short methodology section, which explains the articles' selection and literature review process. Afterward, the current status of IT/IS related research in V4 is presented, then the articles included in the special issue are overviewed, and finally some conclusions and directions for future research are offered.


Preface (S. Luryi, J. M. Xu, and A. Zaslavskyix ). 1. PHYSICS: THE FOUNDATIONS1. Is Fault-Tolerant Quantum Computation Really Possible (M. I. Dyakonov )? Quantum Computation 'Future of Microelectronics' (P. Hawrylak). Semiconductor Spintronics: Progress and Challenges (E. I. Rashba). Towards Semiconductor Spin Logic (I. Zutic and J. Fabian). Molecular Meso- and Nanodevices: Are the Molecules Conducting (N. B. Zhitenev)? The Problem of a Perfect Lens Made From a Slab: With Negative Refraction (A. L. Efros). Is There a Linewidth Theory for Semiconductor Lasers (B. Spivak and S. Luryi)? Fermi Liquid Behavior of GaAs Quantum Wires (E. Levy, A. Tsukernik, M. Karpovski, A. Palevski, B. Dwir, E. Pelucchi, A. Rudra, E. Kapon, and Y. Oreg). 2. BIOLOGY: WE ARE ALL ZOA. Towards Molecular Medicine (H. van Houten and H. Hofstraat). Interfacing the Brain - With Microelectronics (A. V. Nurmikko, W. R. Patterson, Y.-K. Song, C. W. Bull, and J. P. Donoghue)? Synthetic Biology: Synthesis and Modification of a Chemical Called Poliovirus (S. Mueller, J. R. Coleman, J. Cello, A. Paul, E. Wimmer, D. Papamichail, and S. Skiena). Guided Evolution in Interacting Microchemostat Arrays for Optimization of Photobacterial Hydrogen Production (R. H. Austin, P. Galajda, and J. Keymer). Improvements in Light Emitters by Controlling Spontaneous Emission: From LEDs to Biochips (C. Weisbuch, A. David, M. Rattier, L. Martinelli, H. Choumane, N. Ha, C. Nelep, A. Chardon, G.-O. Reymond, C. Goutel, G. Cerovic, and H. Benisty). 3. ELECTRONICS: CHALLENGES AND SOLUTIONS. Nanomanufacturing Technology: Exa-Units at Nano-Dollars (M. R. Pinto). 32 nm: Lithography at a Crossroad (J. P. H. Benschop). Physical Limits of Silicon CMOS: Real Showstopper or Wrong Problem (M. Brillouet)? Will the Insulated Gate Transistor Concept Survive Next Decade (O. Engstrom). Scaling Limits of Silicon CMOS and Non-Silicon Opportunities (Y. Nishi). Carbon-Nanotube Solutions for the Post-CMOS-Scaling World (P. M. Solomon). Alternatives to Silicon: Will Our Best Be Anywhere Good Enough in Time (M. J. Kelly)? MRAM Downscaling Challenges (F. Arnaud d'Avitaya, V. Safarov, and A. Filipe). Atomically Controlled Processing for Future Si-Based Devices (J. Murota, M. Sakuraba, and B. Tillack). Ultimate VLSI Clocking Using Passive Serial Distribution (M. Banu and V. Prodanov). Origin of 1/f Noise in MOS Devices: Concluding a Noisy Debate (K. Akarvardar, S. Cristoloveanu, and P. Gentil). Quasiballistic Transport in Nano-MOSFETs (E. Sangiorgi, S. Eminente, C. Fiegna, P. Palestri, D. Esseni, and L. Selmi). Absolute Negative Resistance in Ballistic Variable Threshold Field Effect Transistor (M. I. Dyakonov and M. S. Shur). Formation of Three-Dimensional SiGe Quantum Dot Crystals (C. Dais, P. Kaser, H. Solak, Y. Ekinci, E. Deckhardt, E. Muller, D. Grtzmacher, J. Stangl, T. Suzuki, T. Fromherz, and G. Bauer). Robust Metallic Interconnects for Flexible Electronics and Bioelectronics (D. P. Wang, F. Y. Biga, A. Zaslavsky, and G. P. Crawford). 4. PHOTONICS: LIGHT TO THE RESCUE. Silicon Photonics - Optics to the Chip at Last (D. A. B. Miller)? The Future of Single- to Multi-Band Detector Technologies (M. N. Abedin,I. Bhat, S. D. Gunapala, S. V. Bandara, T. F. Refaat, S. P. Sandford, and U. N. Singh). Terahertz Quantum Cascade Lasers and Real-Time T-Ray Imaging (Q. Hu, B. S. Williams, S. Kumar, A. W. M. Lee, Q. Qin J. L. Reno, H. C. Liu and Z. R. Wasilewski). Terahertz Spectroscopy and Imaging (E. H. Linfield, J. E. Cunningham, and A. G. Davies). Wavelength Tuning of Interband Cascade Lasers Based on the Stark Effect (S. Suchalkin, M. Kisin, S. Luryi, G. Belenky, F. Towner, J. D. Bruno, C. Monroy, and R. L. Tober). Intersubband Quantum-Box Lasers: An Update (D. Botez, M. D'Souza, G. Tsvid, A. Khandekhar, D. Xu, J. C. Shin, T. Kuech, A. Lyakh and P. Zory). A New Class of Semiconductors Using Quantum Confinement of Silicon in a Dielectric Matrix (M. A. Green). Merging Nanoepitaxy and Nanophotonics (N. N. Ledentsov, V. A. Shchukin, and D. Bimberg). Quantum Control of the Dynamics of a Semiconductor Quantum Well (E. Paspalakis, M. Tsaousidou, and A. F. Terzis). List Of Contributors. Index.


Almost 20 years after the remarkable earthquake swarm of 1982, near the town of Enola, Arkansas, with more than 40,000 micro-earthquakes, another event revisited the same North-Central Arkansas region in 2001. Nine years later, in 2010, a huge swarm event shook the northern part of Faulkner County, around the city of Guy. The following year, this seismic swarm event apparently migrated southward towards the city of Greenbrier, with an increase in the number of yearly recorded events. A 13km previously unrecognized, NE trending Guy-Greenbrier basement fault was revealed as a result of these swarm events. Within the vicinity of the Greenbrier earthquake swarm in the eastern Arkoma basin, north of the Ouachita Mountains, the first waste water disposal well became operational in April 2009, and a total of six disposal wells are known to have been operating between 2009 and 2011. The deepest of these was the Wayne Edgmon well, which was injecting above the intersection of the Enders and the Guy-Greenbrier fault. The area experienced an increase in magnitude M ≥2.5 earthquakes during periods of Saltwater Disposal (SWD). The Enola and Greenbrier swarms are known to be in an intraplate setting and the generation of earthquakes in such a setting is uncommon. In the Enola swarm vicinity, a leveling survey in 1986 revealed a rise in measured elevation within the Paleozoic graben, where the swarm hypocenters are located, and correlated as a possible cause. The Enola sequence still has unanswered questions and the Guy-Greenbrier swarm raises the possibility to find answers to these questions. Though both swarms are tectonically and geologically related, they do not seem to have similar triggering mechanisms as there were no disposal wells in the study area prior to 1982. The recent NGS levelling survey showed insignificant changes in elevation, thus graben uplift is still considered a triggering mechanism for the Enola swarm. With the onset of SWD wells and increase in seismicity between the towns of Guy and Greenbrier during the same time, as well as responses to the seismic profiling questions in regards to background seismicity, injection practices, temporal and spatial correlations, the Greenbrier appears to be an induced event, while the Enola event appears to be unrelated to human activity.


All metastases start out small, and treatment is more likely to be effective if the disease is detected at an early stage, so the current focus of imaging is to improve our ability to find small lesions. Sixty years ago, the most effective instrument for detecting liver metastases was the surgeon's hand during laparotomy. J C Goligher, a former colleague in Leeds, followed up about 700 patients after resection of primary colorectal cancers, and found 31 whose livers appeared normal at surgery, but who came to autopsy within one month. Five of these (16%) were found to have unsuspected liver metastases. Forty years ago, Ozada & Pickren examined 150 autopsy livers containing metastases and found that in 11% of cases, the organs appeared normal to inspection and palpation but showed deep-seated tumours on sectioning. Twenty years ago, it became clear from follow up studies after resection of colorectal cancer that about one third of patients in whom the liver appeared normal at the time of laparotomy would develop detectable liver metastases within two years. Observation of tumour growth rates indicates that the lesions were almost certainly present in the liver at the time of surgical examination. During the last 20 years, non-invasive imaging techniques have improved to the degree that they are now at least as accurate as direct surgical examination of the liver, and even with the addition of intra-operative ultrasound (IOUS) it is now relatively uncommon for our surgical colleagues to discover lesions at the time of operation that were not already detected by earlier imaging. In a current study in my own department, 20% of patients undergoing liver resection with IOUS were found to have 'new' metastases on CT in within 6 months. All this suggests that surgical findings at laparotomy no longer represent a suitable standard of reference for measuring the accuracy of imaging. In order to show further improvements in imaging, we need a more sensitive reference standard.

The increasing use of surgical resection for liver metastases, particularly from colorectal primaries, gives us an opportunity to correlate imaging with histology in more detail, but there are still limitations here. Conventional pathologic examination of gross liver specimens involves slicing the organ at 1 cm intervals, but then employing the same methods as those used by the surgeons at laparotomy—visual inspection, and palpation. Pathologists may run into the same problem faced by the radiologist with CT and MRI—that of missing lesions which are smaller in size than the thickness of the slice. The obvious answer is to use thinner slices both in imaging and in pathologic examination. This could lead to a rather odd situation (which seems to be happening in my own institution) where we radiologists think we are detecting more and more small liver lesions, but the pathologist, using thinner slices to examine the resected liver segments, is also finding more smaller lesions, so our rates of detection are apparently not improving.

Until recently, studies describing the accuracy of imaging techniques did not usually indicate the size distribution of the lesions they found, so sensitivity could not be related to size. Recent work indicates that with colorectal liver metastases, careful MRI or CT should detect 95% or more of lesions larger than about 15 mm. The real issue now is the accuracy of detection for lesions smaller than this. One possible approach, which would be independent of the quality of the pathologic gold standard, would be to look at the distribution of sizes amongst the lesions detected. A presentation at the recent ESGAR/SGR meeting reported that almost 60% of colorectal liver metastases were smaller than 20 mm at the time of detection, and 30% were smaller than 10 mm. If we can further increase the proportion of lesions that are detected at this size range we can be confident that our imaging techniques are improving.

The next problem we run into is the relatively frequent incidence of small benign lesions in the liver. Studies dating back several years have shown that the majority of sub-centimetre lesions found on CT, even in patients with established malignant disease, remain stable over prolonged observation and appear to be benign, although pathologic confirmation is rarely obtained. With multislice CT we are finding more and more smaller and smaller lesions, which poses the same difficulty as that created by the introduction of lung CT over 20 years ago—most of these tiny lesions are benign, but their imaging characteristics are overlapping and in some cases indistinguishable from those of metastases. With MRI, benign features are often demonstrable, but even so, the prevalence of small benign malformations in the liver adds an extra level of difficulty to the recognition of sub-centimetre metastases. Although we will continue to improve the detection and characterisation of sub-centimetre lesions, there seems to be no prospect with current imaging methods of finding liver metastases smaller than about 2 mm. But do we need to?

Imaging is used not only to detect disease but also to localise it. The main objective of localisation (possibly the only objective) is to allow treatment by local measures—whether surgery, radiotherapy, or other forms of ablation. These types of treatment are only applicable to disease of macroscopic dimensions, so once we are dealing with sub-millimetre metastases, localisation may become unimportant and only detection is needed to allow systemic or regional chemo- or immuno-therapy. We already know that colorectal liver metastases, even when they are too small to be detected by surgical examination at laparotomy or by conventional imaging, produce changes in the relative proportions of arterial and portal venous inflow into the liver. This disturbance in liver perfusion was first shown 20 years ago by nuclear medicine techniques, and later by Doppler ultrasound. At the time, the mechanism for this blood flow disturbance was not known, but the more recent demonstration of angiogenesis in tumours of sub-millimetre size explains these early perfusion changes. So far, the perfusion techniques have not found wide usage, mostly because the original encouraging results have been difficult to reproduce in other centres. This is partly explained by the fact that as with other physiological measurements, the range of normal variation is enough to obscure small pathologic changes. Further, it is not clear how much tumour mass is needed to create the degree of perfusion disturbance which can be measured externally, so even if these approaches were reproducible and reliable, we still need to establish the size range of lesions which might be detectable.

Finally, the natural history of metastases at an even earlier stage of growth is gradually being unravelled. Experimental work on small animals many years ago showed that very large numbers of tumour emboli injected into the portal vein would produce only a few liver metastases, suggesting the presence of active biological defence mechanisms. Recent work from a group in Boston, summarised at ESGAR/SGR by Dr Kurskal, used an elegant technique of direct optical microscopy of the mouse liver in vivo to demonstrate the sequence of events at cellular level following the release of tumour cells into the portal circulation. In brief, they found that cancer cells were not mechanically trapped in portal venules, but were phagocytosed by Kupffer cells which then released cytokines, causing changes in the local vascular endothelium which allowed tumour cells to bind to and subsequently migrate through the vessel walls to establish invasive growth. Although further elaboration of the mechanisms involved is awaited, even these early results suggest new approaches for detection by molecular imaging techniques and for novel treatments.

In summary, we should now be able to detect, with careful use of current MRI and CT, the vast majority of colorectal liver metastases larger than 1–2 cm. In order for imaging to be equally effective for lesions in the 2–20 mm size range, we need to pursue further refinements in our existing technologies. Lesions in the size range of 0.2–2 mm are more likely to be treated by regional or systemic immuno- or chemo-therapy, so we don't need to worry about localising them, only about detecting their presence. This might best be achieved by exploiting the perfusion changes associated with tumour angiogenesis, but our techniques need to be more robust than they are at present, and we also need to explore the specificity of these vascular changes since similar perfusion disturbances occur in other forms of liver disease. For lesions at the earliest stage of growth (20–200 µ), it appears likely that detection will require the recognition of specific molecular or genetic markers and again it will be the specificity of these markers which determine the feasibility of detection by imaging, with PET being the most likely of our current techniques to contribute.