Background: Continuously deeper reform of public hospitals has put forward the need to innovate the philosophy and system of large medical equipment operation and management, and the phenomenon featuring "more attention to purchasing and less attention to management" need to be turned around. Methods: This research took use of information management to set up ID fields (unique number) for target stand-alone equipment; integrated statistics functions of HIS, PACS, LIS, RIS and equipment management system to get the basic operation data; informationized the work flow and reform technology to set up a post evaluation indictor system for the performance of stand-alone equipment; compared the service condition of newly purchased equipment with the feasibility application of relative department from various dimensions; designed objective post-evaluation indicators from various angles to scientifically manage existing medical equipment and support decision-making of new application for purchasing medical equipment. Results: Application performance of stand-alone equipment and clinical departments were ranked in a standardized manner. Decision-making mode based on data case of stand-alone equipment was set up. Net present value was evaluated. However, re-purchasing the instrument did not continuously increase the contribution of each instrument. The laboratory can purchase new instruments again, while the imaging department is not recommended to purchase. Conclusion: The performance evaluation mechanism based on information construction for large stand-alone medical equipment and its support for decision-making of purchasing is of great significance to improve the service life of equipment, exert the maximum effect and reduce economic waste.


The Lorentz oscillator model is well-known for its effectiveness to describe the far infrared optical properties of ionic materials. The parameters including oscillator strength and damping factor in the model are usually obtained by fitting to experimental results. In this paper, a new method, based on static and dynamic first-principle simulations, is developed to parameterize the Lorentz oscillator model with the initial atomic structure as the only input parameter. This method is then applied to predict the far infrared reflectance of GaAs, which shows excellent agreement with experimental measurements.Copyright © 2011 by ASME


On 18-19 June 2007, the BIS held its Sixth Annual Conference, on "Financial systems and macroeconomic resilience", in Brunnen, Switzerland. The event brought together senior representatives of central banks, academic institutions and the private sector to exchange views on this topic. This BIS Paper contains the opening address by William R. White (Economic Adviser, BIS), the contributions to the policy panel on "Coping with financial distress in a more markets-oriented environment" and the prepared remarks of the participants at the overview panel of the conference. The participants in the policy panel discussion were Donald Kohn (Board of Governors of the Federal Reserve), Armýnio Fraga (Gývea Investimentos) and John Gieve (Bank of England). Yi Gang (People's Bank of China), Stanley Fischer (Bank of Israel) and Lucas Papademos (European Central Bank) participated in the overview panel, which was chaired by Malcolm Knight (BIS).


Smartphone overuse is related to a variety of issues such as lack of sleep and anxiety. We explore the application of Self-Affirmation Theory on smartphone overuse intervention in a just-in-time manner. We present TypeOut, a just-in-time intervention technique that integrates two components: an in-situ typing-based unlock process to improve user engagement, and self-affirmation-based typing content to enhance effectiveness. We hypothesize that the integration of typing and self-affirmation content can better reduce smartphone overuse. We conducted a 10-week within-subject field experiment (N=54) and compared TypeOut against two baselines: one only showing the self-affirmation content (a common notification-based intervention), and one only requiring typing non-semantic content (a state-of-the-art method). TypeOut reduces app usage by over 50%, and both app opening frequency and usage duration by over 25%, all significantly outperforming baselines. TypeOut can potentially be used in other domains where an intervention may benefit from integrating self-affirmation exercises with an engaging just-in-time mechanism.


Output growth, investment and the real interest rate in long-run evidence tend to be negatively affected by inflation. Theoretically, inflation acts as a human capital tax that decreases output growth and the real interest rate, but increases the investment rate, opposing evidence. This paper resolves this puzzle by requiring exchange for investment as well as consumption. Inflation then decreases the investment rate, and still decreases both output growth and real interest up to some moderately high rate of inflation, above which increasingly low investment finally causes capital to fall relative to labour, and the real interest rate to rise.


Many governments use price and tax subsidization to meet social protection objectives in lieu of, or in addition to, direct income transfers. Such subsidies may be perceived as influencing behavior to further other socially desirable policies. For example, the price response induced by lowering the price of schooling or key food items will both lower the cost of living for the beneficiaries and also increase the investment in education or health more than a similar income transfer would achieve. Governments may also choose price subsidies because they are easier to administer than income transfers. In many cases they may also be politically more tractable. The most common form of price subsidy is a direct, untargeted subsidy. However, various other means may be used to deliver price subsidies as well. Untargeted indirect price subsidies, exemptions on value added or other sales taxes, dual exchange rates, export taxes, producer quotas, subsidies on transport and storage, and domestic sales of a commodity below international opportunity cost are all forms of subsidization. While such subsidies do lead to increased consumption towards a commodity in keeping with policy objectives, they usually also distort production incentives. Subsidies on goods available in a rationed amount are a less costly alternative to open ended subsidies on the entire supply of a good. The incidences of benefits from a general price subsidy are proportional to purchases and can be deduced from a survey of expenditures. For many commodities, including most grains commonly consumed, wealthier households receive larger transfers in absolute terms, yet the amount of transfer a poor household receives will be a larger share of its budget. Some goods, such as meat, are inappropriate vehicles for redistribution since subsides on them will not only accrue mainly to the rich they will actually increase inequality in welfare. On the other hand, some governments have chosen to subsidize goods for which consumption declines as incomes increase. These are termed selftargeted commodities. There is substantial evidence that food subsides do affect nutrient consumption in a manner different than income transfers. The reduced price will have a direct influence on purchases of commodities with general subsidies and for rations that exceed the amount normally purchased. But even in the case of quotas and food stamps there is evidence that the presence of food related transfers encourages increased consumption, possibly due to changes in the share of resources controlled by women. Successfully implementing subsidy programs presents many administrative challenges. Among the most critical is limiting the sale of subsidized commodities in the higher priced general market. Substantial leakages have been documented recently in several countries. Technology such as optically scanned smart cards can provide costeffective monitoring mechanisms, and is equally suitable for use with rations and in twotier price systems, but may be less appropriate for poor communities without sources of power for scanning devices. Reforms that separate the government's role as financier from the market's role of providing services have the potential to be the most effective. If, in addition, governments recognize that food policy objectives are often achieved more effectively by delivering income support without any direct or indirect ties to food commodities, reforms can be separated from the consumption of a given commodity or use of a given market channel. This increased flexibility often allows for better targeting as well as an increased likelihood that the transfers will result in the poorest beneficiaries being lifted out of poverty. The nature and timing of subsidy reforms depend on many factors, including the interplay of diverse interests expressed by local groups and international agencies. Balancing the different interests is not easy, but country experiences suggest several factors contribute to public acceptance of reforms, including advanced publicity, introducing credible safety nets policies to protect the vulnerable, and implementing reforms during periods of favorable international commodity prices.


Posterior reversible encephalopathy syndrome (PRES) is a neurological disorder that can affect all age groups. It appears to have a higher incidence in the female population. Some common risk factors include hypertension, electrolyte abnormalities, sepsis, and chemotherapeutic medications such as Obinutuzumab. Our patient, who had chronic lymphocytic leukemia (CLL), presented with altered mental status. She was recently started on Obinutuzumab less than a week before this presentation. MRI findings were consistent with PRES, including diffuse vasogenic cerebral edema predominately throughout the bilateral parietal and occipital lobes associated with some edematous extension into the posterior part of bilateral frontal lobes. This case aims to highlight the importance of early diagnosis by appropriately identifying the MRI features of PRES to improve patient quality of life and decrease morbidity and mortality.


The largest school building programme in the history of Scotland is taking place from 2000 - 2011 to extensively refurbish or replace 21% of local authority schools. Thereafter, the Scottish government has pledged to improve all schools remaining in poor or bad "condition" or "suitability" (Scottish Government, 2009). Based on the School Estate Statistics 2010 (Scottish Government, 2010), 36% of the school estate could still require improvement work. As the first stage in this long term building programme draws to a close, it is necessary to reflect on the performance of new and refurbished school buildings in meeting the requirements of 21st century education. This paper argues that further research is required to establish the strengths and weaknesses of accessible design in Scotland's new and refurbished schools. Reference is made to relevant national and global educational initiatives, such as "Inclusive Education" and "Education for Sustainable Development", and changes to the national curriculum in the form of the new Curriculum for Excellence. A brief summary of Scottish government design guidance also helps to establish the requirements of the built environment in helping to deliver modern education. "Improving the School Estate" (Audit Scotland, 2008), the most comprehensive study of new and refurbished school buildings in Scotland, found the worst performing factors to be lighting, temperature, acoustics, and air quality. The adverse effects that these factors can have on all people, and particularly those with impairments or additional support needs, are examined. It is concluded that further investigations within the area of accessible design in Scotland's new and refurbished schools should be undertaken in order to achieve an inclusive, inspirational, and sustainable learning environment for current and future generations.


Abstract Technological networks (e.g., telephone and sensor networks, Internet) have provided modern society with increased efficiency, but have also exposed us to the risks posed by their vulnerability to attacks. Mitigating these risks involves designing robust network topologies in situations where resources are economically constrained. In this study, we consider the vulnerability of network topologies from an economic viewpoint and propose security metrics, which are necessary for assessing the efficiency of our solutions. We define the vulnerability of a network as the potential loss in connectivity due to the actions of a strategic adversary. To derive vulnerability metrics, we revisit our recently introduced network blocking game models, which provide a framework for quantifying network topology vulnerability in adversarial environments. We assume that the network operator takes both security and economic goals into consideration. To model these goals, we generalize previous models by introducing usage costs and budget constraints for the operator. We study two natural constraint formulations, the maximum and the expected cost constraints, and derive the feasible vulnerability/cost region. Because the proposed metrics are based on game-theoretic models, computing them can be challenging. To elucidate these challenges, we provide a thorough complexity analysis for solving the proposed games.


Dramatic images from the Hubble Space Telescope reveal the details of a galaxy that was distorted into the shape of a wagon wheel when a smaller galaxy plunged into it. The images show massive balls of gas reeling like comets around the galaxy's center. Presumably formed from the debris of the cataclysm, the megacomets may help scientists better understand the strange physics of galactic collisions.


In this Introduction, the author discusses how the collection of essays provide insightful analysis of biological, legal, and public health issues surrounding mandatory testing of pregnant women and infants for HIV. As background, beginning in February 1, 1997, New York ordered that every newborn in the state be tested for HIV-antibodies. In addition, the results are disclosed to the delivering mother, her physician, and her child's physician, thus raising difficult ethical and policy questions for the Symposium panel.


To combat the rapid infection rate of today's Internet worms, signatures for novel worms must be generated soon after an outbreak. This is especially critical in the case of polymorphic worms, whose binary representation changes frequently during the infection process. In this paper, we examine the assumptions underlying two leading network-based signature generation systems for polymorphic worms: polygraph [14] and Hamsa [12]. By identifying an assumption of both systems not met by all vulnerabilities, we discover a class of vulnerabilities (feature omission vulnerabilities) that neither system can accurately characterize. We demonstrate the limitations of polygraph and Hamsa by testing the signatures that they generate for exploits targeting a feature omission vulnerability. We discuss why feature omission vulnerabilities are difficult to characterize and how increased semantic awareness can help the signature generation process.


The MSP/RON signaling pathway favors the conversion of micrometastatic lesions to overt metastases by suppressing antitumor immune responses. The loss of RON functions in the host potentiates tumor-specific CD8+ T-cell responses, hence inhibiting the outgrowth of metastatic cancer cells. Thus, RON inhibitors may potentially prevent the outgrowth of micrometastases in cancer patients.


In June-July 2012, observations were carried out using the recently upgraded, large-aperture, Rayleigh-scatter lidar system located at the Atmospheric Lidar Observatory (ALO) on the campus of Utah State University, in Logan, UT (41.7 N, 111.8 W). This time period was significant because it enabled us to observe the annual temperature minimum in the upper mesosphere-lower thermosphere region. The data collected during the campaign were analyzed for temperatures between ~70-109 km. The results above ~95 km are the first obtained with a Rayleigh-scatter lidar, extending the technique well into the lower thermosphere. A great deal of variability from night-to-night is evident in these temperature profiles and in the mesopause altitude. The profiles also show considerable wave activity from large amplitude waves. The temperatures are compared to those from the MSISe90 model and from the 11-year ALO temperature climatology. This new capability for the ALO Rayleigh lidar, like any new observational capability, opens the potential for new discoveries in this hard-to- observe region.


The Farnesoid X Receptor (FXR) has recently moved into the spotlight through the release of clinical data using Obeticholic Acid, an FXR agonist, that demonstrated effectiveness of this bile acid-like drug in patients with Primary Biliary Cirrhosis and Non-alcoholic Steatohepatitis (NASH). FXR holds the promise to become an attractive drug target for various conditions, from Non-alcoholic Fatty Liver Disease (NAFLD), NASH, liver cirrhosis, portal hypertension and a variety of cholestatic disorders to intestinal diseases including inflammatory bowel disease and bile acid diarrhea. Despite the wide therapeutic potential, surprisingly little is known about the pharmacology, pharmacokinetics and tissue distribution properties of drugs targeting FXR. Are tissue specific FXR agonists preferable for different indications, or might one type of ligand fit all purposes? This review aims to summarize the sparse data which are available on this clinically and pharmacologically relevant topic and provides a mechanistic model for understanding tissue-specific effects in vivo.


The loss in Gonzales v. Carhart and the rhetoric the Court employed point to a significant vulnerability in the movement for legal protections for women's reproductive health care - its conflicts over motherhood. This Article argues that the movement's failure to emphasize that abortion serves women's interest in, and respect for, motherhood divides it from its constituents and creates the vulnerability that the anti-abortion movement now exploits, contributing to the reduction of constitutional protections for abortion. Embracing abortion's supportive relationship to motherhood is essential to the survival of the abortion right, as well as to the vitality of our continuing battle to redefine motherhood in conditions of equality. In Section I of the paper, I explore the ways women's respect for the importance of motherhood and "bonds of love" with their children inform their decisions to obtain abortions. In Section II, I summarize the state of abortion jurisprudence, paying particular attention to the Court's vision of women's need for, or "interest in," abortion. I trace the emergence of the Court's discomfort with women's decision-making about abortion, linking it with decreasing protections for the right and increasing recognition that abortion serves an interest in women's social and economic equality. I demonstrate that the Court's increasing recognition that abortion serves an interest in self-determination that could result in a rejection of the role of mother, accompanied a decreasing recognition of abortion's importance to women's interests in motherhood itself, an interest in how any child they bear is cared for. This sense in which abortion serves women's interests in motherhood was last seen in Planned Parenthood v. Casey, where the Court acknowledged that the choice to have an abortion could be seen as reflecting "human responsibility and respect for [human life]." In Section III, I discuss Gonzales v. Carhart and argue that while the ruling itself is limited and much of the Casey standard remains intact, the decision reflects this diminishing sense of abortion as serving the woman's interest in motherhood. The Court's opinion reflected a view that abortion destroys motherhood, rather than the view that abortion enhances motherhood and enables women to mother their children in the best conditions possible, and in conditions closer to equality.Finally, in Section IV I explore resistance in the feminist movement to stressing the ways abortion serves a woman's interest in, and respect for, the importance of motherhood. Despite real risks of appealing to and thus supporting regressive notions of motherhood, I make both normative and prescriptive claims that given the centrality of concerns for motherhood in women's decision-making about abortion, we must emphasize that women's interest in abortion in a constitutional sense includes not only her interest in her choice not to be a mother (an aspect of her decisional autonomy), her interest in her personal dignity, her interest in her health and life (an aspect of her bodily integrity), and her interest in privacy of the information about her decision, but also includes her interest in motherhood itself and in deciding how she will mother any child she bears. I contend that these arguments about why women choose and why women need abortions can and should be made within, and not as an alternative to, a rights framework. Stressing that abortion serves women's interest in motherhood in a constitutional sense very clearly falls within such a framework, and is necessary to drawing a complete picture of the importance of abortion to women's liberty, equality, and dignity. It strengthens the woman's right to abortion and is vital to continued protection of the right under any level of scrutiny or in any constitutional framework.


An approach to nonmonotonic inference, based on preference orderings between possible worlds or states of affairs, is presented. We begin with an extant weak theory of default conditionals; using this theory, orderings on worlds are derived. The idea is that if a conditional such as "birds fly" is true then, all other things being equal, worlds in which birds fly are preferred over those where they don't. In this case, a red bird would fly by virtue of red-bird-worlds being among the least exceptional worlds in which birds fly. In this approach, irrelevant properties are correctly handled, as is specificity, reasoning within exceptional circumstances, and inheritance reasoning. A sound proof-theoretic characterisation is also given. Lastly, the approach is shown to subsume that of conditional entailment.


An abstract program is a formal specification that describes the valid behavior of a distributed program without describing particular implementation mechanisms that achieve this behavior. Valid behavior can be modeled as the possible sequences of events that may be observed of a conforming concrete implementation of the abstract program. In this paper, we address the problem of how to select event sequences from an abstract program to test its concrete implementation. Sequencing constraints make explicit certain types of required properties that are expressed only implicitly by an abstract program. The sequencing constraints derived from an abstract program can be used to guide the selection of event sequences during testing. We describe a constraint notation called CSPE and show how to achieve coverage and detect violations of abstract CSPE constraints. Abstract constraints address the problem of how to compare two programs written at different levels of abstraction. Results of an empirical study of CSPE-based testing are reported.


A filter binding assay was developed to study interactions between purified TRAP, the trp RNA-binding attenuation protein of Bacillus subtilis, and trp specific transcripts. TRAP formed stable complexes with trpEDCFBA leader RNA; binding was L-tryptophan-dependent and was complete within 60 s. TRAP binds to a segment of the trp leader transcript that includes part of an RNA antiterminator structure. Binding to this segment allows formation of an RNA terminator structure, thereby promoting transcription termination. Using several trpEDCFBA leader deletion transcripts, we identified several closely spaced trinucleotide repeats (seven GAG and four UAG repeats) in the trp leader transcript that appeared to be required for TRAP binding. We also showed that TRAP binds to a segment of the trpG transcript that includes the trpG ribosome binding site; the nucleotide sequence of this segment contains several appropriately spaced trinucleotide repeats (seven GAG, one UAG, and one AAG). TRAP binding to the trpG transcript would block translation initiation. RNA footprint analysis confirmed interaction between TRAP and the trinucleotide repeats in the various transcripts. TRAP, in the presence or absence of L-tryptophan, appears to consist of 11 or 12 identical 8-kDa subunits. Our findings suggest that each tryptophan-activated TRAP subunit can bind one G/UAG repeat in a target transcript. Multiple protein-RNA interactions are required for stable association.


Low temperature (25 °C–80 °C) synthesis of zinc oxide (ZnO) nanoparticles (,20 nm) at short synthesis periods (;30 min) was achieved by precipitation. The precipitation system was formed using zinc acetate dihydrate as zinc source, ethylene glycol (EG) as solvent and polyvinyl pyrrolidone (PVP) as chelating agent. The size of spherical ZnO nanoparticles was manipulated by the choice of precipitation temperature (13.0 6 1.9 nm at 25 °C and 9.0 6 1.3 nm at 80 °C), which essentially changes the nature of adsorption events between ZnO crystals and organic molecules. The particle size can also be regulated by the amount of chelating agent as a result of further enhancement in adsorption between ZnO crystals and organic additives. The spherical ZnO nanoparticles were agglomerated into triangular form when different solvent was used–by substituting water for EG, which has different adsorption ability. Accordingly, formation and growth mechanisms controlling the size and morphology of ZnO nanoparticles have been proposed.


The study overall concerns the age-rounding process in the Latin inscriptions, which has triggered the interest of the researchers starting with the 19 th century. The first part of this study deals with the age-rounding process in the province of Moesia Inferior, by comparing the data with those provided for other Lower Danube provinces, differentiated on gender. The second part of this study presents the age-rounding process depending on the legal status of the deceased by using Whipple's Index. The values of age rounding are close to those obtained for the other Lower Danube provinces. It is worth mentioning that there are more ages ending in 0 and 5 than in other digits. Concerning the legal status, the age-rounding process is less accentuated in the case of citizens and


We report polarization mode dispersion measurements on a 168 km long undersea optical cable, performed with two techniques. From experimental results, statistical behavior of polarization parameters and their time fluctuations have been extracted. An average differential group delay of about 13 ps shows that dispersion-shifted fibers can be affected by a polarization dispersion significantly larger than standard step-index fibers. The correlation length of the polarization-coupling perturbation in the tested fibers is not negligible with respect to the link length.


Coesite and diamond in metamorphic rocks point to their very deep burial, but these minerals do not allow a precise derivation of metamorphic pressure–temperature ( P – T ) conditions at ultrahigh pressure (UHP). Thermodynamic calculations of mineral equilibria can accomplish this task when it is possible to assign mineral compositions to a former UHP equilibrium state. Pressure–temperature pseudosections are superior, because they often permit the construction of P – T paths to and from UHP conditions only on the basis of chemically zoned minerals such as garnet and phengite. The examples of a metapelite from Oman and an eclogite from the Erzgebirge, Germany, illustrate this method, but also demonstrate its limits. The derived paths are the basis for further geodynamic modeling and insight into tectonic processes.


Mobile robots offer a typical example of systems with nonholonomic constraints. Several controllers have been proposed in the literature for stabilizing these systems. However, few experimental studies have been reported comparing the characteristics and the performance of these controllers with respect to neglected dynamics, quantization, noise, delays, etc. In this paper, we use a Khepera mobile robot to perform experimental comparison of several control laws. Khepera has two dc motor-powered wheels and introduces many realistic difficulties, such as different motor dynamics for the two wheels, time delay, quantization, sensor noise, and saturation. We emphasize the implementation difficulties of two discontinuous controllers proposed herein, and we compare their performance with several other controllers reported in the literature. Ways to improve the performance of each controller are also discussed.


By using a remotely operated vehicle (ROV), we studied large mucous aggregates produced by the larvacean Bathochordaeus in Monterey Bay, California. These fragile structures or "houses," cannot be sampled by typical water or net collecting devices, and likely represent a class of cosmopolitan, widely spaced aggregates in subsurface waters. ROV samples allowed us to determine the contribution of the aggregate‐associated communities to populations of microorganisms at depths of 100–500 m. Because the giant houses only average ˜1 per 100 m3, they harbor <1% of the microorganisms in the water, although they are locally enriched. However, once abandoned, houses may play a significant role in transporting materials and organisms to depth. Flux calculations indicate they may seasonally account for 11–100% of some classes of sinking materials at 500 m. These calculations are based on house‐flux contributions predicted from house age (estimated), house abundance (ROV measured), and particle flux (measured by a nearby sediment trap). Based on our ROV observations of spatial and temporal characteristics of the giant aggregates, we calculate the probability that sediment traps collect the correct number of sinking aggregates. Our results suggest that rare particles, such as large aggregates and some sarcodines and pteropods, may be undersampled by commonly used, small sediment traps. Furthermore, the predictably infrequent capture of such comparatively rare particles can lead to erroneous interpretations of temporal or spatial patterns in the flux of material through the upper ocean.


The mammalian neocortex is organized into unique areas that serve functions such as sensory perception and modality-specific behaviors. The sizes of primary cortical areas vary across species, and also within a species, raising the question of whether area size dictates behavioral performance. We show that adult mice genetically engineered to overexpress the transcription factor EMX2 in embryonic cortical progenitor cells, resulting in reductions in sizes of somatosensory and motor areas, exhibit significant deficiencies at tactile and motor behaviors. Even increasing the size of sensorimotor areas by decreasing cortical EMX2 levels can lead to diminished sensorimotor behaviors. Genetic crosses that retain ectopic Emx2 transgene expression subcortically but restore cortical Emx2 expression to wild-type levels also restore cortical areas to wild-type sizes and in parallel restore tactile and motor behaviors to wild-type performance. These findings show that area size can dictate performance at modality-specific behaviors and suggest that areas have an optimal size, influenced by parameters of its neural system, for maximum behavioral performance. This study underscores the importance of establishing during embryonic development appropriate levels of regulatory proteins that determine area sizes, thereby influencing behavior later in life.


Restrictive valvulopathy has been reported in association with dopamine agonist therapy in parkinsonian patients. The majority of reports have been related to pergolide, but anecdotal cases following treatment with bromocriptine or cabergoline have also been presented. It is presently unclear whether the potential induction of restrictive cardiac valvulopathy is a class effect of all dopamine agonists or if there is a differential risk between ergot and nonergot compounds. In this study, the frequency of a valvular regurgitation as assessed by routine transthoracic echocardiography was compared between 75 patients with Parkinson's disease (PD) treated with pergolide (n = 29), cabergoline (n = 13), pramipexole or ropinirole (n = 33), and 49 age‐matched nonparkinsonian controls. The exposure to pergolide and cabergoline was associated with higher frequencies of valvular regurgitation grades 2 and 3 (31% and 47%) compared with age‐matched controls (13%), while there was no increase of valvular regurgitation grades 2 and 3 in patients treated with nonergot compounds (10%). Evidence for restrictive valvulopathy was found in one patient treated with pergolide and cabergoline each. While this study shows similarly increased frequencies of valvular regurgitation in patients treated with the ergot agonists pergolide and cabergoline in comparison to both normal controls and patients treated with nonergot agonists, evidence for restrictive valvulopathy was only found in two cases. These results highlight the need for further prospective studies of the prevalence and underlying mechanisms of cardiac valvulopathy in PD patients treated with different dopamine agonists. © 2006 Movement Disorder Society


Surgery is the removal of obstructions and replacement or realignment of structures allowing the body to heal itself. What can micromachining add to this practice? Devices smaller than achieved before which are good for detecting problems, removing obstructions so biological repair can commence, and creating structures (scaffolds) for speeding repair. With the advent of micromachining industry can begin to create devices which are similar in size to the cells themselves. This will allow the creation of devices which mimic biology, for example needles as small as a mosquito's, valves the size of tiny blood vessels, or structures which allow cells to grow creating new functioning tissue.
 Micromachining's promise allows the engineer to take into account the cells' "view" of devices. Devices can now be made as small as a red blood cells (8μ) and with passages of 50μ, critical for healthy cell growth. In pores larger than this cells can't bridge the space for transport of nutrition, oxygen, carbon dioxide, etc. In smaller pores cells clog the passageways and get quickly trapped.
 The mechanical design engineer can use micromachining to:
 • See things: diffraction gratings, lenses, optical elements
 • Filter things: segregate cells, move drugs and nutrients without moving the cells
 • Do work: move/remove tissue, make tiny surgical tools, make tiny nozzles for water jet cutting
 • Support things: make scaffolds for cells, stent open body passages
 • Make surfaces biologically friendly: textured surfaces, surfaces filled with materials friendly to the cells
 • Make better tools: sharper cutting edges, tiny mechanisms, valves, controls
 These and other possible micromachined devices will be discussed.


Out of 22 isolates of Fusarium subglutinans f. sp. ananas tested in preliminar trials, it was selected for the final experiment four isolates representing the resistant group (E272, E274, E279 e E283), and four representing the susceptible group (E285, E277, E278 e E290) of Fusarium subglutinans f. sp. ananas to benomyl. The isolates were collected on diseased pineapple plants from the southern area of the Espirito Santo State, and inoculated on three months old pineapple (Ananas comosus) seedlings, cv. Perola (susceptible) and Primavera (resistant), under greenhouse conditions, to study the virulence of the pathogen. The pineapple seedlings were inoculated by immersion of the seedlings in a conidial suspension (105 conidia/ml) scratched from PDA plates, after they had been injured on their crown area. The results showed that the cv. Primavera was resistant to all isolates tested. The cv. Perola showed symptoms of fusariosis 15 days after the inoculation with the isolates resistant to benomyl. The isolates susceptible to benomyl caused symptom of the disease 45 days after the inoculation. The isolate E272 (resistant to benomyl) was the most virulent isolate to cv. Perola, whereas the isolates E277 and E278 (susceptible) to benomyl were the least virulent. The susceptible isolates to benomyl caused symptoms of the disease on the cv. Perola 45 and 60 days after the inoculation. In conclusion this study showed that there are differences in virulence between the isolates of F. subglutinans f. sp. ananas resistant and susceptible to benomyl to pineapple.


A simple analytical dose rate calculation model based on primary and scatter separation that treats 192Ir as a monoenergetic source by use of appropriate attenuation and mass energy absorption coefficients is documented for accurate dosimetry in water. This model is then generalized and tested for use in any homogeneous tissue material of radiobiological interest using scatter to primary ratios calculated in water with a material density scaling to account for the difference in the scattering properties of these materials and water. The potential of the analytical model for predicting the effect of the interference of an inhomogeneity is then evaluated by comparison with corresponding Monte Carlo calculations. It is found that regardless of the inhomogeneity dimensions and position relative to the source, the model is capable of increased accuracy (better than 2%) in calculating the primary dose rate at any point not only for low-Z tissue materials but also for high-Z shielding materials where a severe hardening of the primary photons occurs. Overall, for low-Z tissue inhomogeneities the proposed model succeeds in correcting dosimetry results towards the right direction compared to commercial treatment planning systems that currently ignore the effect of phantom dimensions and inhomogeneity interference. Regarding high-Z shielding materials the proposed model accurately predicts the dose reduction just beyond the inhomogeneity (for example it predicts a dose reduction of 47% just behind a tungsten alloy cylinder of 1 cm diameter and 2 mm thickness placed at 1.4 cm away from an 192Ir source, in agreement with corresponding results in the literature) but does not account for the increasing contribution of the laterally scattered photons with increasing distance from the bounded inhomogeneity.


In this paper, we introduce the Jones polynomial of a graph $G=(V,E)$ with $k$  components as the following specialization of the Tutte polynomial: $$J_G(t)=(-1)^{|V|-k}t^{|E|-|V|+k}T_G(-t,-t^{-1}).$$ We first study its basic properties and determine certain extreme coefficients. Then we prove that $(-\infty, 0]$ is a zero-free interval of Jones polynomials of connected bridgeless graphs while for any small $\epsilon>0$ or large $M>0$, there is a zero of the Jones polynomial of a plane graph in $(0,\epsilon)$, $(1-\epsilon,1)$, $(1,1+\epsilon)$ or $(M,+\infty)$. Let $r(G)$ be the maximum moduli of zeros of $J_G(t)$. By applying Sokal's result on zeros of Potts model partition functions and Lucas's theorem, we prove that \begin{eqnarray*}{q_s-|V|+1\over |E|}\leq r(G)<1+6.907652\Delta_G \end{eqnarray*} for any connected bridgeless and loopless graph $G=(V,E)$ of maximum degree $\Delta_G$ with $q_s$ parallel classes. As a consequence of the upper bound, X.-S. Lin's conjecture holds if the positive checkerboard graph of a connected alternating link has a fixed maximum degree and a sufficiently large number of edges.


Traumatic brain injury (TBI) is the leading cause of death and disability in young adults. Survivors of TBI frequently suffer from long‐term personality changes and deficits in cognitive and motor performance, urgently calling for novel pharmacological treatment options. To date, all clinical trials evaluating neuroprotective compounds have failed in demonstrating clinical efficacy in cohorts of severely injured TBI patients. The purpose of the present review is to describe the utility of animal models of TBI for preclinical evaluation of pharmacological compounds. No single animal model can adequately mimic all aspects of human TBI owing to the heterogeneity of clinical TBI. To successfully develop compounds for clinical TBI, a thorough evaluation in several TBI models and injury severities is crucial. Additionally, brain pharmacokinetics and the time window must be carefully evaluated. Although the search for a single‐compound, 'silver bullet' therapy is ongoing, a combination of drugs targeting various aspects of neuroprotection, neuroinflammation and regeneration may be needed. In summary, finding drugs and prove clinical efficacy in TBI is a major challenge ahead for the research community and the drug industry. For a successful translation of basic science knowledge to the clinic to occur we believe that a further refinement of animal models and functional outcome methods is important. In the clinical setting, improved patient classification, more homogenous patient cohorts in clinical trials, standardized treatment strategies, improved central nervous system drug delivery systems and monitoring of target drug levels and drug effects is warranted.


British Islam and English Law presents a novel argument about the nature and place of groups in society. The encounter with Islam has led English law to tread a line between two theoretical models, liberal individualism and multiculturalism, competing for dominance over the law of organised religion. This philosophical rivalry has generated a set of seemingly intractable conflicts between individual and community, religion and state, nation and culture. This book resurrects the long-buried theory of classical pluralism to address and resolve these tensions. Applying this to five understudied institutions that give structure and form to British Islam – banks, charities, schools, elections, clans – it outlines and justifies the reforms that would optimise the relationship between law and religion. Unflinching and unorthodox, this book places law and theory in context, employs innovative methods such as nudge theory and applied history, and provides detailed answers to hard questions about British Islam.


Rapidly expanding fed aquaculture demands high-quality, sustainable nutrient sources for utilisation as dietary ingredients. Exploring the potential of under-utilised resources from other industries is imperative to replace finite natural resources, such as fish meal. Marine gammarids may be an excellent source of essential fatty acids; however, their aquaculture using formulated diets remains untested in terms of survival, growth and nutritional value of the cultured product. Here, juveniles of 2 marine gammarid species, Gammarus locusta and Echinogammarus marinus, were maintained in controlled feeding experiments with 2 marine diets (Ulva spp. and Fucus spp.) and 2 terrestrial diets (lupin meal and carrot leaves). G. locusta exhibited higher survival rates, particularly when fed carrot leaves, an agricultural waste product. Fatty acid profiles of the resulting G. locusta product appear well suited for marine finfish nutrition, indicating high suitability of G. locusta as an aquaculture diet source. In contrast, whilst E. marinus may provide beneficial fatty acid profiles for aquatic animal nutrition, its poor growth performance in this study indicates that further dietary/culture research is required for this species. Our results indicate, for the first time, that marine gammarids are capable of trophic upgrading and can use non-marine diets for healthy growth in culture, but their suitability as a formulated feed ingredient for specific fish or crustacean species needs to be investigated individually. Future research should include the development of optimal large-scale production as well as investigation of optimal methods of inclusion of gammarids as feed ingredient for target aquaculture species.


As a country faced with many socio-economic challenges government intervention prompting protests are not unique to South Africa. In light of these confining circumstances, requests from various economic agents, especially labour unions have been directed towards the implementation of a national minimum wage (NMW). Although theory advocates negative effects from minimum wages, international evidence regarding these labour market interventions shows conflicting outcomes. The main aim of the study was to analyse business owners' perceptions regarding the impact of the implementation of a NMW. A qualitative research approach was adopted to collect data with a total of 10 in-depth interviews conducted with business owners in the Vaal Triangle region, Gauteng. The results of the study showed that participants acknowledged the advantage of implementing a NMW, perceiving the intervention as a much needed step towards greater equality. Other perceived advantages involved the security a NMW provides job-seekers and the possible impact on improved demand for goods and services as higher wages stimulate the economy. Concerns however were raised regarding small firms' ability to cover these wages and the capability of the legislation to account for inherent skill differences in various sectors. The findings of the study provide valuable insights especially in the South African context and even more so from a demand side perspective regarding the possible impact of these labour market interventions.


Introduction: Āyurvedā has described three types of Deśa viz. Jāngal , Ānup and Sādhāraṇa. Deśa also known as Bhūmī refers to the natural inhabitant of an individual. It has a major role in examination of disease as well as a diseased person. In Āyurvedic diagnostic method importance is given to Deśa Parikṣa while interrogating to patients because climate, food, constitution and diseases vary according to Deśa (habitat). Marāṭhawāḍā is an administrative part of Mahārāṣtrā state of India. It is having different climate than other regions of the state such as Konkan, Ghāt area, Khāndeśa, Vidarbha etc. Methods: This paper is an attempt to critically analyze the Marāṭhawāḍā region of the state considering present climate condition and geography in comparison to the concept of Āyurvedic Deśa description. Authentic government web portals of this region were visited to know the present climatic situations. Various research papers were also reviewed to discern the territory from other part of the state. Results: After scrutinizing the facts over past few years; it has been found that most of the region of Marāṭhawāḍā falls under deficit (below average) rainfall terrain. Flora and fauna is similar to that of dry land. Conclusion: Marāṭhawāḍā province of Mahārāṣtrā state can be compared with Jāngal Deśa rather than Sādhāraṇa Deśa.


Systems that can efficiently search collections of sign language videos have been highlighted as a useful application of sign language technology. However, the problem of searching videos beyond individual keywords has received limited attention in the literature. To address this gap, in this work we introduce the task of sign language retrieval with free-form11The terminology "natural language query" is commonly used to describe unconstrained textual queries in spoken languages. However, since sign languages are also natural languages, we adopt for the term "free-form textual query" instead. textual queries: given a written query (e.g. a sentence) and a large collection of sign language videos, the objective is to find the signing video that best matches the written query. We propose to tackle this task by learning cross-modal embeddings on the recently introduced large-scale How2Sign dataset of American Sign Language (ASL). We identify that a key bottleneck in the performance of the system is the quality of the sign video embedding which suffers from a scarcity of labelled training data. We, therefore, propose SPOT-ALIGN, a framework for interleaving iterative rounds of sign spotting and feature alignment to expand the scope and scale of available training data. We validate the effectiveness of SPOT-ALIGN for learning a robust sign video embedding through improvements in both sign recognition and the proposed video retrieval task.


Context: Sodium nitrite (NaNO2) in blood is highly reactive with haemoglobin (Hb), thus affecting hematopoiesis and induction of methemoglobinemia. Aim: This study was conducted to determine the effect of chlorophyll from katuk (Sauropus androgynus) leaves on the level of Hb, Malondialdehyde (MDA), ferritin, and schistocytes percentage in female mice induced NaNO2. Settings and Design: Experimental research was conducted using 24 female mice strain Balb-c. Methods and Material: NaNO2 0.3 ml/head/ day given during 18 days, while the chlorophyll or Cu-chlorophyllin as much as 0.7 ml/head/day given the following day for 14 days. Statistical analysis used: Results are reported as mean values ± SD and statistically analyzed by One Way Anova test with 95% significance level. Results: The Hb levels of blood plasma in the control group, NaNO2 induction, induction NaNO2 and chlorophyll of katuk leaves (NaNO2+katuk), induction of NaNO2 and Cu-chlorophyllin from K-LiquidTM (NaNO2+Cu-chlorophyllin) in sequence is 13.29 g/dl; 11.83 g/dl; 14.54 g/dl; 13.99 g/dl, whilst the MDA levels in each group is 2.10 ± 0.11 mol/L, 3.44 ± 0.38 mol/L, 2.31 ± 0.18 mol/L, 2.31 ± 0.13 mol/L, and the ferritin levels is 62.71 ± 6.42 ng/ml; 63.22 ± 7.59 ng/ml; 67.45 ± 8.03 ng/ml, and 64.74 ± 7.80 ng/ml, respectively. The fragment schistocytes percentage's in each group is 0%, 0.11%, 0.01%, 0.03%. The ferritin levels tend to increase in NaNO2+katuk. Mann Whitney test results obtained no significant difference in Hb, MDA level and schistocytes percentage between the groups of mice that received NaNO2+katuk NaNO2+Cu-chlorophyllin (p>0.05). This indicates that chlorophyll from S. androgynus leaves as effective as Cu-chlorophyllin in decrease the MDA levels after NaNO2 treatment, and although not significant, it can increase ferritin levels. Conclusion: The antioxidant activity of chlorophyll from katuk leaves are able to decrease schistocytes percentage's and MDA level. The increasing of Hb and ferritin level indicates its potential in the treatment of haemolityc anaemia. Further studies aimed at the mechanisms of action of this chlorophyll are needed.


D Saini and M Ali University of Wollongong Wollongong 2522 Australia CVD coatings have been traditionally used for enhancing the life of cemented carbide tools in machining operations. Due to several inherent advantages over CVD coatings, more recently the PVD coatings have been employed on cutting tools for improvement of their wear resistance and performance in machining operations. Significant variability in the tool life and performance of PVD coated tools has, however, been observed by several researchers. Such variability in tool life, which is a big hindrance in successful automation as well as planning of machining operations, is considered to result from a combination of factors including poor adhesion between substrate and coating, less than optimum design of coating architectures, increased diffusion wear at high temperatures and thermal softening of the hard coatings. This paper presents an investigation, which examines several novel architectures of PVD coatings for their suitability for high speed turning operations. Amongst the various coatings (TiN, TiC, TiCN and TilTiNffiCNffiC) investigated, TiC coating was observed to have the longest tool life and relatively better performance compared to the other coatings.


OBJECTIVE
To use proteomic analysis to identify qualitatively and quantitatively mammalian protein components of commercial veterinary vaccines against canine distemper, leptospirosis, borreliosis, and rabies.

SAMPLE
25 licensed veterinary vaccines (from 4 different manufacturers) against canine distemper and leptospirosis, borreliosis, and rabies (3-year and 1-year durations of immunity).

PROCEDURES
Duplicate samples from a single-lot vial of each vaccine were prepared by acetone precipitation and proteolysis with trypsin and Lys-C protease mix. Peptides mixtures (1 μg) were analyzed by liquid chromatography-tandem mass spectrometry using an Orbitrap Fusion Lumos mass spectrometer. Liquid chromatography-tandem mass spectroscopy data were searched against a Bos taurus protein database using MaxQuant to identify and quantify mammalian proteins in the vaccines. Identified proteins were classified by function and network analysis to visualize interactions.

RESULTS
The largest number of mammalian proteins was identified in 3-year rabies vaccines (median, 243 proteins; range, 184 to 339 proteins) and 1-year rabies vaccines (median, 193 proteins; range, 169 to 350 proteins). Borrelia and leptospirosis-distemper (L&D) vaccines had the lowest number of proteins. Rabies vaccines had the highest number of identified proteins in common (n = 316); 33 were unique to 1-year products and 44 were found in 3-year products. Borrelia and L&D vaccines had 16 and 22 uniquely identified proteins, respectively. The protein classifications were primarily modulators of protein-binding activity, enzymes, transfer-carrier proteins, cytoskeletal proteins, defense-immunity proteins, calcium-binding proteins, and extracellular matrix proteins.

CLINICAL RELEVANCE
This study demonstrates proteomics application to evaluate quality differences among different vaccines, identifying potential stimulants of desirable and undesirable immune responses.


Subway station is the key node in the urban rail transit system. Its level of service affects directly the subway's operation efficiency and traveller's choice of track traffic way to travel. Considering the facility characteristics in subway station and pedestrians perspective, on the basis of a large number of survey data, this paper identifies the facilities which impact the level of service in subway station mainly, takes safety, comfort and smoothness as evaluation index, and evaluates respectively from the entrance, channel and platform area. The judgment matrix of facilities condition influence in each region on pedestrians is constructed and the evaluation model of level of service in subway station has been built based on the facility state. Finally taking PingGuoYuan subway station as instance for analysis, the result verifies that the evaluation method is effective.


More and more biologically inspired robots present spines with multiples degrees of freedom to resemble their biological counterparts. The function of the spine on both animal and robot can play an important role in locomotion. If it has enough degrees of freedom to allow independent control of both shoulder and pelvic girdle (i.e., the points of attachment of body and limb), it can be used to extend the reach of the legs or to increase turning capabilities. In this letter, we present the spine controller for a sprawling quadrupedal robot. The controller achieves a synchronization between spine and legs and allows a precise control of the girdle positions by solving the inverse kinematics of the spine. The controller is validated in simulation and experiments with the real robot showing an ease in the control of the locomotion and achieving a very good tracking between the girdle trajectories with a very small, noncumulative error (less than 6% of the inter-girdle distance). This controller enables both the human operation and the implementation of autonomous path planning and navigation algorithms for these type of amphibious robots, making them more suitable for scenarios with limited maneuverability such as inside pipes or in collapsed buildings.


The design of services and their corresponding business models (BMs) aims at a value creation for customers and service providers. Thus, the outcome is interrelated. However, both – the design service systems and BMs – are evaluated separately because they do not have a common theoretical foundation. Therefore, this design science research aims at the development of an evaluation scheme for the design of services and BMs. Building on a general systems theory, we conceptualize human-centered service systems (HCSSs) and their corresponding BMs as a coherent system. This conceptualization gives the possibility to provide concrete analytical levels that allow an integrated evaluation of this system. We apply this evaluation scheme in a care service context and show that the integrated evaluation allows a more concrete assessment of the combined design of HCSS and the corresponding BMs. With this evaluation scheme, we offer an operationalization of a summative evaluation for the design of HCSSs and BMs as an artifact. Also, this provides a new perspective on theory-rooted knowledge for designing and evaluating service systems. For practitioners, the evaluation results allow the coordination of the value proposition in the service systems and BMs.


COVID-19 Pandemic has become a major problem in various infected countries, including Indonesia. The proper risk communication strategy during this outbreak was important to reduce the impact. Therefore, this research was intended to assess the potential use of Google Trends as a tool to monitor risk communication during COVID-19 pandemic in Indonesia. Search patterns were analyzed using the terminology used to identify COVID-19 in Indonesia, followed by information-finding keywords 'gejala (symptoms)', 'mencegah (preventing)', and 'obat (drug)' keywords compared to the number of newly confirmed COVID-19 cases in Indonesia using time-lagged correlation analysis from December 31th, 2019 to April 20th, 2020. Peaks within respective timelines were qualitatively described according to current COVID-19 related events. "Corona" was the terminology mostly used in Indonesia to identify COVID-19. There were five spikes observed from "corona" keyword timeline, which each spike was dependent on the media coverage and regulation by the Government. Validation using time-lagged correlation yields significant results between corona, corona symptoms, preventing corona and corona drugs compared to newly confirmed COVID-19 cases in Indonesia. Google Trends can potentially be used to maximize the improvement of risk communication and as a tool to monitor public restlessness during the COVID-19 pandemic in Indonesia by Government.


The Mainstreaming on Ambient Intelligence (MonAMI) project, funded under the European Commission's IST e-Inclusion work programme (FP6 framework), set out to demonstrate that accessible, useful services for older, and disabled people can be delivered using mainstreamed systems and platforms. An open platform, based on an Open Services Gateway initiative (OSGi Alliance™, 2011), framework, was developed to deliver a bouquet of Ambient Assisted Living services. The services were developed with a Design for All (European Commission, 2000) approach, in consultation with potential users in the following areas:
•
Monitoring: home (environmental and appliance control), health.

•
Time management.

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Safety and security: safety at home, visitor validation, activity detection.

•
Communication and networking.

The platform integrated elements from reliable self-organizing networks, wearable devices, user interaction technology, monitoring capability, and service infrastructures and delivered services on mainstream devices such as broadband internet and third-generation mobile telephones. In addition, to facilitate use and user interaction, the consortium designed an innovative user interface (UI), using Universal Control Hub architecture (Zimmerman, 2009).

The services were first tested by older and disabled users in laboratory settings in six feasibility and usability centres across Europe (France, Germany, Slovakia, Spain, Sweden, and the UK). Once the platform, services and UI were found to be feasible, usable, and appropriate to user needs, a living-scale field trial was carried out in three communities (Kosice, Slovakia; Stockholm, Sweden; and Zaragoza, Spain), where 70 users, 45 carers, and 14 care staff employed the services in users' homes over a three-month period. In addition to testing the scalability of the platform, the trial evaluated the services' potential of meeting the long-term care needs of older and disabled people and the support needs of caregivers. The commercial viability and economic effects on long-term care financing were also evaluated in order to understand the impact of mainstream implementation of the MonAMI concept, as part of the Ambient Assisted Living Open Association (AALOA, 2010) initiative. The MonAMI project ran for 57 months and came to completion in May, 2011.


BACKGROUND
 The rise in pediatric obesity and its accompanying condition, type 2 diabetes (T2D), is a serious public health concern. T2D in adolescents is associated with poor health outcomes and decreased life expectancy. Effective diabetes prevention strategies for high-risk adolescents and their families are urgently needed.

 OBJECTIVE
 The aim of this study was to co-design a diabetes prevention program for adolescents by using human-centered design methodologies.

 METHODS
 We partnered with at-risk adolescents, parents, and professionals with expertise in diabetes prevention or those working with adolescents to conduct a series of human-centered design research sessions to co-design a diabetes prevention intervention for youth and their families. In order to do so, we needed to (1) better understand environmental factors that inhibit/promote recommended lifestyle changes to decrease T2D risk, (2) elucidate desired program characteristics, and (3) explore improved activation in diabetes prevention programs.

 RESULTS
 Financial resources, limited access to healthy foods, safe places for physical activity, and competing priorities pose barriers to adopting lifestyle changes. Adolescents and their parents desire interactive, hands-on learning experiences that incorporate a sense of fun, play, and community in diabetes prevention programs.

 CONCLUSIONS
 The findings of this study highlight important insights of 3 specific stakeholder groups regarding diabetes prevention and lifestyle changes. The findings of this study demonstrate that, with appropriate methods and facilitation, adolescents, parents, and professionals can be empowered to co-design diabetes prevention programs.


The exemplum is a privileged target for the cultural study of the medieval society. If the research regarding the content of those edifying anecdotes is already well advanced, the analysis of the real audiences and concrete uses of the exempla remained yet to be undertaken. Because the expansion and characterization of this typology is directly linked with the emergence of the collections of exempla, our investigation was based on this kind of works. To succeed with this project, we used the information existing in the manuscripts copies and in medieval booklists. With these two kinds of sources, we analysed books as physical objects (cover, writing, etc.), vehicles of culture (versions, surrounding works, etc.) and historical witness (purchase, legacies, etc.). The thesis focused on the following central questions: how did books of exempla diffused in time and space? Which works achieved success? Who were the owners of these books? How did they read and use them? In the first part of our analysis, the theoretical one, historiographical and historical definitions of the exemplum and the collections of exempla have been clarified. This was indispensable because a large part of the scientific literature, especially in France, only considered the exemplum as a kind of story, which appeared in the twelfth century and was used by preachers in sermons to illustrate a salutary message. By saying so, they neglected the persuasive nature of the exemplum, confining it to a literary genre. In reality, the exemplum should be primarily considered as a rhetorical argument based on a deed or a word that happened in the past. Nevertheless, its persuasive power, which comes from its visual imagery, is especially effective when the case is told in the form of a story. This phenomenon is currently studied in the storytelling management, which uses stories to improve communication. In sum, the exemplum is an argument stemming from reality in the form of a story. The history of the exemplum does not start with the mendicant orders, but within democracy and the rhetoric schools of Athena and later in Rome. With the emergence of Christianity, church fathers use it to fight against heretics and monks to share the spiritual experience of elders to novices. A pro domo use of the exempla appears with the creation of the new religious orders, first Cluny, then the Cistercians and finally the mendicants. The latter put exempla in theirs sermons to attract the attention of their audience, though not only. They use them in conversations, lectiones and also in didactic and moral treatises. This was no novelty: previous writers such as John of Salisbury in his Polycraticus uses it abundantly. If the years 1250-1350 are the magnificent era of the exemplum, since the second half of the 14th century, we can notice a decline of the exemplum, which becomes either an illustration, an allegory, or an open, facetious, entertaining or devote story. As far as the books of exempla are concerned, for a long time scholars did not try to define them precisely. They looked at these collections only for the stories they contained. To their minds, an exempla collection was simply a book in which there were exempla. To make a necessary distinction between very differing books of exempla, we need to precise: a) the proportion of exempla; b) if the exempla are used by the authors as arguments or offered to the readers for rhetorical purposes; c) if there is an organizational system. Those questions successively allow distinguishing books of exempla from books with exempla, exempla treaties from exempla collections and exempla repositories. Nonetheless, due to the fact that exemplum is not a genre but a function, it is very hard to define a clear corpus. The first important book of exempla comes from Roman Antiquity. The Facta et dicta memorabilia of Valerius Maximus was used as a text book for students in rhetoric. With the flourishing of monasticism, exempla collections of the Vitae patrum spread all over the Christian world, diffusing the good examples of the desert Fathers. In the beginning of the second millennium, religious orders continued this practice, but with the new will of putting their respective orders forward. The first alphabetical repositories of exempla appear at the end of the 13th century due to the necessity of preaching and of tidying up growing knowledge. However, alongside the existence of these collections of exempla made for preaching purposes, there are many others books and treaties of exempla, whose function is either to instruct, or to give the rules of social morality, or simply to edify readers. The second part of the thesis puts the stress on the concrete diffusion and uses of the exempla collections. The investigation on the manuscript copies shows, inter alia, an increase in their number during the centuries (13 times more in the 15th than in the 13th century), the predominant place of the German area, especially in the 15th century, and the growing importance of the treatises of exempla, taking advantage on the repertories. With regards to the incunabula, we count 172 Latin and 74 vernacular editions of exempla collections before 1500. This mainly concerns repositories for the former when the latter contains almost exclusively treaties. The production of this edition starts in the years 1470, culminates in the years 1480 and declines at the end of the century. Geographically, we notice the same importance of the German speaking area, especially in the city of Strasbourg. At the second place we find Italy, which produces mainly antique exempla collections. For the manuscript copies as for the incunabula editions, we have to keep in mind that it exists huge differences of success between books of exempla. The last chapter focuses on the diffusion and uses of the books of exempla written by the Dominicans, the biggest producer of such collections. We also see big discrepancies of success, owners and uses. For example, the Gerard of Frachet's Vitas fratrum were mainly read in continental Europe by Dominicans and Canons regular to keep conventual order and morality, while the John Herolt's Promptuarium exemplorum was used by different orders and persons in the German world for pastoral purposes and John of Bromyard's Summa praedicantium was located in England in highly intellectual institutions, such as universities and big Benedictine monasteries. A collection of exempla can also have different readers and uses. Thomas of Cantimpre's Bonum universale de apibus, written for conventual purposes, was also used either as a repertory of exempla for preaching or as a treaty of social morality. John of Cessoles' Liber de moribus was not only read by preachers and pastors but also by lay people as spiritual lecture. Across the study of the different exempla collections, we notice many German 15th century manuscripts exclusively elaborated for pastoral uses. In these Priesterhandbucher we can find, next to exempla collections, sermons, artes predicandi, treaties on the Mass, explanation of the sacraments, the Ten Commandments and Credo. Unlike a common vision of exempla collections produced and used within the preaching, this global study shows, on the one hand, the great diversity of production environments and aims intended by exempla compilers, as well as, on the second hand, an equally important variety concerning diffusion and real uses of such works. Added to the thesis, there is an appendix of more than 300 pages presenting 68 Latin books of exempla, in which the characteristics of the work are exposed, the objectives of use pursued by the author, and the modalities of diffusion (including the list of manuscripts, medieval mentions, translations and editions).


A variety of new physics models predict heavy resonances that decay to multiple hadronic jets. These models include axigluons, colorons, diquarks, excited quarks, Randall-Sundrum gravitons, string resonances, and Z' models, among others. Other models make the prediction that high-pT jets will be suppressed, resulting in jet extinction. Using the data collected in 2012 at a center-of-mass energy of 8 TeV, the CMS collaboration has made a baseline inclusive jet cross section measurement for comparison with new-physics searches, and then performed searches for jet extinction and resonances that decay to two hadronic jets. The results of these searches will be presented. No evidence of new physics has been observed, and these results set new limits on the parameters of these models.


Survey interview languages not only determine who is eligible to participate in certain surveys but may also influence survey estimates. We examined potential biases arising from the exclusion of linguistic minorities using the 2003 California Health Interview Survey (CHIS), a multilingual survey. Although 88.3 percent of the interviews were conducted in English, results show that surveys using only English are likely to produce large differences in estimates. When survey interviews are conducted in English and Spanish, the overall difference may disappear, but the survey results for Asians remain unchanged. This implies that surveys conducted only in English may not adequately represent the general population and differences in estimates for Asians may exist even if English and Spanish are used.


This article presents an example of how one hospital reports the results of activity-based costing (ABC). It examines the composition and supporting assumptions of an ABC report for a particular procedure in the operating room (OR). It describes management uses of the information generated. It comments upon how the continuous quality improvement (CQI) is synchronized with the ABC reporting.


Small theropod post-cranial material from Tendaguru, Tanzania, the only known Late Jurassic theropod locality in the Southern Hemisphere, is reviewed. Material originally described as 'coelurosaurs' includes at least one taxon of basal tetanuran and one taxon of small abelisauroid. Together with the abelisauroid Elaphrosaurus and the presence of a larger ceratosaur in Tendaguru, this material indicates that ceratosaurs were an important faunal element of Late Jurassic East African theropod faunas. One bone furthermore shares derived characters with the holotype of the poorly known Middle Jurassic Australian theropod Ozraptor and allows the identification of the latter as the oldest known abelisauroid, thus indicating an early divergence of ceratosaurids and abelisauroids within ceratosaurs. Abelisauroids might have originated in Gondwana and represent important faunal elements of Cretaceous Gondwanan theropod faunas in general.


Laminin is a heterotrimeric glycoprotein that plays a central role in promoting neutrophil chemotaxis, motility, and attachment to basement membrane. Rabbit peritoneal exudate neutrophils stain positively for laminin, which is presumed to be of exogenous origin and bound to laminin receptors on the cell surface. We examined 32Dc13 cells, a murine neutrophil precursor cell line, by immunoprecipitation. Northern blot analysis, flow cytometry, and electron microscopy for the endogenous production of laminin. Our results demonstrate that 32Dc13 cells endogenously produce a laminin B2 chain protein and messenger RNA (mRNA) without producing any detectable A or B1 chain protein or mRNA. The B2 chain protein was not secreted by the cells; rather it could be detected on the cell surface after treatment of cells with neuraminidase. These findings suggest the possibility of a novel role for the laminin B2 chain in myeloid development and function.


Written from a mathematical standpoint accessible to students, teachers, and professionals studying or practicing in engineering, mathematics, or physics, the new second edition is a comprehensive introduction to the theory and application of transformations. Presenting the more abstract foundation material in the first three chapters, Geometric Transformations in 3D Modeling reduces the clutter of theoretical derivation and development in the remainder of the text and introduces the operational and more application-oriented tools and concepts as the need arises. It assumes the reader has already taken analytic geometry and first-year calculus and has a working knowledge of basic matrix and vector algebra. This self-contained resource is sure to appeal to those working in 3D modeling, geometric modeling, computer graphics, animation, robotics, and kinematics. Explores and develops the subject in much greater breadth and depth than other books, offering readers a better understanding of transformation theory, the role of invariants, the uses of various notation systems, and the relations between transformations. Describes how geometric objects may change position, orientation, or even shape when subjected to mathematical operations, while properties characterizing their geometric identity and integrity remain unchanged. Presents eigenvalues, eigenvectors, and tensors in a way that makes it easier for readers to understand. Contains revised and improved figures, with many in color to highlight important features. Provides exercises throughout nearly all of the chapters whose answers are found at the end of the book.


Tectonic subsidence of the Cordilleran miogeocline in the western United States during late Proterozoic through early Paleozoic time is best explained by rifting and subsequent thermal contraction of the lithosphere. The tectonic component of subsidence can be calculated by removing the isostatic effects of sediment and water loading. The resultant subsidence curves indicate that rifting began about 600 m.y. ago and that extension of the lithosphere during rifting was in excess of a factor of 1.3.


To dissect the individual effects of the four non-MHC, autosomal loci (Bxs1 to Bxs4) that contribute to SLE susceptibility in BXSB mice, we generated congenic lines from chromosome 1 on a C57BL/10.YBXSB (B10.Yaa) background for the intervals (values in megabases (Mb)) Bxs1 (46.3-89.2 Mb), Bxs1/4 (20.0-65.9 Mb), Bxs1/2 (64.4-159.0 Mb), and Bxs2/3 (105.4-189.0 Mb). Glomerulonephritis, qualitatively similar to that seen in the parental BXSB strain, developed in three of these congenic strains. Early onset, severe disease was observed in B10.Yaa.BXSB-Bxs2/3 congenic mice and caused 50% mortality by 12 mo. In B10.Yaa.BXSB-Bxs1/4 mice disease progressed more slowly, resulting in 13% mortality at 12 mo. The progression of renal disease in both of these strains was correlated with the level of anti-dsDNA Abs. B10.Yaa.BXSB-Bxs1 mice, despite their genetic similarity to B10.Yaa.BXSB-Bxs1/4 mice, developed a low-grade glomerulonephritis in the absence of anti-dsDNA Abs. Thus, Bxs4 directed an increase in titer and spectrum of autoantibodies, whereas Bxs1 promoted the development of nephritis. The Bxs2 interval was linked to the production of anti-dsDNA Abs without concomitant glomerulonephritis. In contrast, the Bxs3 interval was sufficient to generate classic lupus nephritis in a nonautoimmune–prone strain. Immune phenotype differed between controls and congenics with a significant increase in B220+ cells in BXSB and B10.Yaa.BXSB-Bxs2/3, and an increase in CD4 to CD8 ratio in both BXSB and B10.Yaa.BXSB-Bxs1/4. Disease in the Bxs3 mice was delayed in comparison to the BXSB parental strain, emphasizing the necessity for multiple interactions in the production of the full BXSB phenotype.


The nature of vulnerability to agricultural drought in three study blocks of Bolangir district in western Orissa has been analysed. The indexing and vulnerability profile method have been used for assessing the nature of drought vulnerability, coping capacity and risk. The study has revealed that the three most influential biophysical factors of drought vulnerability are: rainfall variability, drought intensity and shortage of available waterholding capacity of soil and the three most influential socioeconomic factors are: low irrigation development, poor crop insurance coverage and smaller forest area. It is found that while drought risk varies widely across the study blocks and drought vulnerability and physical exposure to drought vary moderately, the coping capacity of study blocks differ marginally. However, the level of coping capacity has been found significantly lower than the level of drought risk and vulnerability in the study blocks.


SUMMARY Weather conditions and social contact patterns provide some clues to understanding year-round influenza epidemics in the tropics. Recent studies suggest that contact patterns may direct influenza transmission in the tropics as critically as the aerosol channel in temperate regions. To examine this argument, we analysed a representative nationwide survey dataset of contact diaries with comprehensive weather data in Taiwan. Methods we used included model-free estimated relative changes in reproduction number, R 0; relative changes in the number of contacts; and model-based estimated relative changes in mean contacts using zero-inflated negative binomial regression models. Overall, social contact patterns clearly differ by demographics (such as age groups), personal idiosyncrasies (such as personality and happiness), and social institutions (such as the division of weekdays and weekend days). Further, weather conditions also turn out to be closely linked to contact patterns under various circumstances. Fleeting contacts, for example, tend to diminish when it rains hard on weekdays, while physical contacts also decrease during weekend days with heavy rain. Frequent social contacts on weekdays and under good weather conditions, including high temperature and low absolute humidity, all might facilitate the transmission of infectious diseases in tropical regions.


We introduce the notion of a summable fractal curve generated by a finite family of affine operators. This generalizes well-known notions of affine fractals and continuous fractal curves to the case of non-contractive operators. We establish a criterion for the existence of a fractal curve for a given family of operators, obtain criteria for that curve to belong to various function spaces and derive formulae for the exponents of regularity in those spaces as well as asymptotically sharp estimates for the moduli of continuity. These results are applied to the study of well-known curves (Koch, de Rham, and so on), refinable functions and wavelets. We also study the local behaviour of continuous fractal curves. We obtain a formula for the exponent of local regularity of continuous fractal curves at a given point and characterize the sets of points with a fixed local regularity. It is shown that the values of the local regularity of any fractal curve fill out some closed interval. Nevertheless, the regularity is the same at almost all points (in the Lebesgue measure) and can be computed from the Lyapunov exponent of certain linear operators. We apply this technique to refinement equations and compactly supported wavelets. As an example, we compute the moduli of continuity and exponents of local regularity and -regularity for several Daubechies wavelets.


Abstract In the frontal part of the south Pyrenean Eocene thrust-fault system, syn-kinematic fluid flow during the early compressional deformation of the foreland basin marls is evidenced macroscopically by the abundance of calcite shear veins within the thrust-fault zones and folds. The geometry and distribution of the veins are indicative of the mechanisms and kinematics of fluid-deformation relationships, and give assessment of the fluid migration paths. The crack-seal mechanism of formation of the shear veins attests to the episodic nature of fault-slip and associated fluid flow in fractures. The distribution of the veins suggests that the main source of fluid was the dewatering of the overpressured, poorly permeable marls from the thrust footwalls, probably related to both (i) vertical compaction due to burial under thrust sheets and (ii) tectonic horizontal shortening. These fluids drained upwards towards the thrust-fault zones, in which they migrated laterally towards the thrust front due to the anisotropy of the fracture permeability in these zones. The geochemistry of the vein-filling minerals and their comparison with the geochemistry and mineralogy of the host marls are indicative of the fluid types, fluid origins, fluid-sediment interactions, and fluid migration paths. The δ34S and 87Sr/86Sr ratio of the host marl calcite and of the calcite and celestite in the veins away from the thrust-fault zones indicate that the original water trapped interstitially in the marls was Eocene seawater. The elemental composition (Ca, Sr, Mg, Mn, and Fe), δ18O, and δ13C of the same samples reveal a change of the pore-water composition from marine to formation water during the early burial stage. Fluid-inclusion analyses of the celestite in the veins reveal the presence of a hot, saline ascending fluid restricted to these discontinuities, where it was mixed with the local formation water. These two types of fluids drained towards the thrust-fault zones where they acquired a higher 87Sr/86Sr ratio, probably related to local fluid-sediment reactions. Indeed, dickite precipitated during cleavage formation in the most intensely strained part of the fault zones, and its formation was probably mainly controlled by stress. δ18O depletion in the calcite from the structurally highest/innermost thrust-fault zones suggests also the influence of meteoric water derived from the emerged part of the belt in these structures. The earlier fluid regime in the Ainsa basin was an intergranular (porous) flow regime (compactional flow) allowing for a pervasive isotopic, and elemental exchange of the marls prior to vein formation. With the onset of compressional deformation, channelized flow along tectonic slip surfaces became dominant.


Service recommendation plays a critical role in fostering the growth of service ecosystems. However, existing methods are mainly in favor of a small number of popular services while newly emerged ones (i.e., newborn services) are largely ignored, which hurts the systems in two aspects. First, the potential of many services, especially the newborn ones, is wasted. Second, service ecosystems highly depending on a few kernel services are not diversified nor robust. To address this issue, we propose to proactively recommend collaborative services for newborn ones. The aim is to illuminate how to use the newborn services and fertilize their proper usages. While this is a cold start problem, frequent collaboration among newborn or dissimilar services makes it more difficult. In this situation, a Divide-and-Conquer approach is adopted utilizing category tags and collaboration records (DCCC). For each newborn service, the approach first produces one ranked list of old services and one list of newborn services, separately. DCCC then merges the two lists into one for recommendation. Experiments over a real-world dataset from ProgrammableWeb demonstrate that the proposed approach achieves significant improvement in recommendation accuracy compared with baseline methods.


The immediate and continuing management of an 'immersion victim' is described in this article. Proper assessment of the patient and the details of cardiopulmonary resuscitation are revised.


Objective. Closed-loop prosthesis interfaces, which combine electromyography (EMG)-based control with supplementary feedback, represent a promising direction for developing the next generation of bionic limbs. However, we still lack an understanding of how users utilize these interfaces and how to evaluate competing solutions. In this study, we used the framework of speed–accuracy trade-off functions (SAF) to understand, evaluate, and compare the performance of two closed-loop user-prosthesis interfaces. Approach. Ten able-bodied participants and an amputee performed a force-matching task in a functional box-and-block setup at three different speeds. All participants were subjected to both interfaces in a crossover study design with a 1 week washout period. Importantly, both interfaces used direct proportional control but differed in the feedback provided to the participant (EMG feedback vs. Force feedback). We estimated the SAFs afforded by the two interfaces and sought to understand how the participants planned and executed the task under the various conditions. Main results. We found that execution speed significantly influenced performance, and that EMG feedback afforded better overall performance, especially at medium speeds. Notably, we found that there was a difference in the SAF between the two interfaces, with EMG feedback enabling participants to attain higher accuracies faster than Force feedback. Furthermore, both interfaces enabled participants to develop flexible control policies, while EMG feedback also afforded participants the ability to generate smoother, more repeatable EMG commands. Significance. Overall, the results indicate that the performance of closed-loop prosthesis interfaces depends critically on the feedback approach and execution speed. This study showed that the SAF framework could be used to reveal the differences between feedback approaches, which might not have been detected if the assessment was performed at a single speed. Therefore, we argue that it is important to consider the speed–accuracy trade-offs to rigorously evaluate and compare user-prosthesis interfaces.


Messenger RNA (mRNA) degradation plays a critical role in regulating transcript levels in eukaryotic cells. Previous work by us and others has shown that codon identity exerts a powerful influence on mRNA stability. In Saccharomyces cerevisiae, studies using a handful of reporter mRNAs show that optimal codons increase translation elongation rate, which in turn increase mRNA stability. However, a direct link between elongation rate and mRNA stability has not been established across the entire yeast transcriptome. In addition, there is evidence from work in higher eukaryotes that amino acid identity influences mRNA stability, raising the question as to whether the impact of translation elongation on mRNA decay is at the level of tRNA decoding, amino acid incorporation, or some combination of each. To address these questions, we performed ribosome profiling of wildtype yeast. In good agreement with other studies, our data showed faster codon-specific elongation over optimal codons and faster transcript-level elongation correlating with transcript optimality. At both the codon-level and transcript-level, faster elongation correlated with increased mRNA stability. These findings were reinforced by showing increased translation efficiency and kinetics for a panel of 11 HIS3 reporter mRNAs of increasing codon optimality. While we did observe that elongation measured by ribosome profiling is composed of both amino acid identity and synonymous codon effects, further analyses of these data establish that A-site tRNA decoding rather than other steps of translation elongation is driving mRNA decay in yeast.


Abstract The specific energy consumption during mechanical refining operation can be reduced by choosing the optimal process parameters in the wood chipping process such that a beneficial pretreatment is obtained. In the case of the utilization of a larger knife-edge angle, which is one such process parameter, the energy reduction is presumably due to the increased compressive loading parallel to the wood fibers. In the present article, a chip damage parameter D of spruce is in focus, which is relevant for cracking parallel to the fibers. D is defined and its dependence on the chip length and edge angle of the chipping knife is analyzed numerically by means of finite element analyses (FEA). The cutting force was measured in a pilot wood chipper for a number of knife-edge angles. There is a good correlation between the experimental results and those of FEA.


The capacitive coupling interference within floating-gate transistors is the main scaling barrier for highly dense NAND Flash memories. In this case study, we propose a simulation-based methodology for the variability modeling, which is caused by line edge roughness in advanced technological nodes. The aim of this work is to present the approach by modeling the threshold voltage disturbance propagation mechanism in a raw memory array, caused by the variability-affected parasitic coupling. The variability aware model is statistically designed for evaluation of the cell-to-cell interference variability impact on disturbances of threshold voltage and the error generation in a 16-nm half-pitch NAND Flash memory.


We used satellite images to examine the calving behavior of Helheim and Kangerdlugssuaq Glaciers, Greenland, from 2001 to 2006, a period in which they retreated and sped up. These data show that many large iceberg-calving episodes coincided with teleseismically detected glacial earthquakes, suggesting that calving-related processes are the source of the seismicity. For each of several events for which we have observations, the ice front calved back to a large, pre-existing rift. These rifts form where the ice has thinned to near flotation as the ice front retreats down the back side of a bathymetric high, which agrees well with earlier theoretical predictions. In addition to the recent retreat in a period of higher temperatures, analysis of several images shows that Helheim retreated in the 20th Century during a warmer period and then re-advanced during a subsequent cooler period. This apparent sensitivity to warming suggests that higher temperatures may promote an initial retreat off a bathymetric high that is then sustained by tidewater dynamics as the ice front retreats into deeper water. The cycle of frontal advance and retreat in less than a century indicates that tidewater glaciers in Greenland can advance rapidly. Greenland's larger reservoir of inland ice and conditions that favor the formation of ice shelves likely contribute to the rapid rates of advance.


Recent evaluations of both temporal and spatial precision in bird migration have called for external cues in addition to the inherited programme defining the migratory journey in terms of direction, distance and fuelling behaviour along the route. We used juvenile European robins (Erithacus rubecula) to study whether geomagnetic cues affect fuel deposition in a medium-distance migrant by simulating a migratory journey from southeast Sweden to the wintering area in southern Spain. In the late phase of the onset of autumn migration, robins exposed to the magnetic treatment attained a lower fuel load than control birds exposed to the ambient magnetic field of southeast Sweden. In contrast, robins captured in the early phase of the onset of autumn migration all showed low fuel deposition irrespective of experimental treatment. These results are, as expected, the inverse of what we have found in similar studies in a long-distance migrant, the thrush nightingale (Luscinia luscinia), indicating that the reaction in terms of fuelling behaviour to a simulated southward migration varies depending on the relevance for the species. Furthermore, we suggest that information from the geomagnetic field act as an important external cue overriding the seasonal effect on fuelling behaviour in migratory birds.


Background There is a critical need for effective health education methods for adolescent smoking prevention. The coproduction of antismoking videos shows promising results for adolescent health education. Objective This study explored the feasibility of a smoking prevention program using the coproduction of antismoking videos in order to empower adolescents in smoking prevention and tobacco control. A smoking prevention program based on coproduction of antismoking videos over eight sessions was implemented in a low-income neighborhood. Methods A mixed methods design with a concurrent embedded approach was used. In total, 23 adolescents participated in the program. During the prevention program, small groups of participants used video cameras and laptops to produce video clips containing antismoking messages. Quantitative data were analyzed using the Wilcoxon signed-rank test to examine changes in participants' psychological empowerment levels between pre- and postintervention; qualitative interview data were analyzed using content analysis. Results Pre- and postcomparison data revealed that participants' psychological empowerment levels were significantly enhanced for all three domains—intrapersonal, interactional, and behavioral—of psychological empowerment (P<.05). Interviews confirmed that the coproduction of antismoking videos is feasible in empowering participants, by supporting nonsmoking behaviors and providing them with an opportunity to help build a smoke-free community. Conclusions Both quantitative and qualitative data supported the feasibility of the coproduction of antismoking videos in empowering adolescents in smoking prevention. Coproduction of antismoking videos with adolescents was a beneficial health education method.


Sofosbuvir along with ribavirin is being widely used for treatment of HCV in Pakistan but it may show delayed response and reoccurrence of disease in some cases. The aim of the study was to investigate pharmacokinetics and concentration effect analysis of sofosbuvir. HCV patients (n=100) received 400 mg sofosbuvir along with low dose or weight based ribavirin (400 mg). Nonlinear mixed effects modeling (NONMEM) and unpaired t-test were used for the association of concentrations and treatment outcomes. Average day 10 sofosbuvir metabolite BM 331007 concentration was higher in patients having haemoglobin nadir value <10 g/dl compared to the patients having heamoglobin nadir value >10 g/dl (5.34 versus 4.87 pmol/106 cells; p=0.03). The average concentration trends of GS331007 at day 10 was towards being higher in the patients achieved sustained virologic response (SVR) as compare to the patients relapsed (5.19 versus 4.86 pmol/106 cells; p=0.05). Sofosbuvir (GS331007) thresholds concentration (suggested at day 10 through receiver operating characteristic curve) was 5.4 pmol/106 cells for SVR (p=0.05) and haemoglobin nadir cells was 6.3 pmol/106 with sensitivity and specificity of >60%. Dosing simulations shows that 400 mg sofosbuvir twice daily produce day 10 concentration range of 5.4 to 6.7 pmol/106 cells. The range of therapeutic values was identified for HCV patients receiving sofosbuvir in combination with ribavirin for 24 weeks, suggesting a potential pharmaceutical basis for individualized therapeutic dosing.