Recently it has been shown that state-of-the-art NLP models are vulnerable to adversarial attacks, where the predictions of a model can be drastically altered by slight modifications to the input (such as synonym substitutions). While several defense techniques have been proposed, and adapted, to the discrete nature of text adversarial attacks, the benefits of general-purpose regularization methods such as label smoothing for language models, have not been studied. In this paper, we study the adversarial robustness provided by label smoothing strategies in foundational models for diverse NLP tasks in both in-domain and out-of-domain settings. Our experiments show that label smoothing significantly improves adversarial robustness in pre-trained models like BERT, against various popular attacks. We also analyze the relationship between prediction confidence and robustness, showing that label smoothing reduces over-confident errors on adversarial examples.


BACKGROUND
Only some studies have directly compared and analyzed the roles of activated partial thromboplastin time (aPTT) and activated clotting time (ACT) in coagulation monitoring during argatroban administration.

OBJECTIVES
This study aims to assess the correlation of argatroban dose with ACT and aPTT values and to identify the optimal coagulation test for argatroban dose adjustment.

METHODS
We evaluated 55 patients on extracorporeal membrane oxygenation (ECMO) who received argatroban for more than 72 hours. The correlation between argatroban dose and aPTT and ACT values was evaluated. To compare argatroban dose and bleeding events according to liver dysfunction, the patients were divided into 2 groups based on alanine aminotransferase and total bilirubin.

RESULTS
Among the 55 patients, a total of 459 doses and coagulation tests were evaluated. The aPTT and ACT values showed a weak correlation with argatroban dose, with the Pearson correlation coefficients of 0.261 (P < 0.001) and 0.194 (P = 0.001), respectively. The agreement between the target 150 to 180 seconds for ACT and 55 to 75 seconds for aPTT was observed in 140 patients (46.1%). Twenty-four patients (43.6%) had liver dysfunction when they started argatroban. The median argatroban dose was lower in the liver dysfunction group than in the control group (0.094 mcg/kg/min vs 0.169 mcg/kg/min, P = 0.020). Difference was not observed between the 2 groups in the amount of red blood cell (0.47 vs 0.43 pack, P = 0.909) and platelet (0.60 vs 0.08 pack, P = 0.079) transfusion per day.

CONCLUSION AND RELEVANCE
A weak correlation was observed between argatroban dose and the aPTT and ACT values. However, the agreement between aPTT and ACT was only 46.1% regarding the scope of target range. Further research is necessary to determine how to assess the optimal argatroban dose for patients administered argatroban while undergoing ECMO at the intensive care unit.


Water is one of the natural wealth that is absolutely needed by living things to survive and maintain health. In facts, water treatment is carried out on the raw water that does not meet the standards of clean water quality, therefore, the non-standardized elements need to be eliminated or reduced so that all water meets the applicable standards. One alternative which is available locally is the use of natural coagulants from plants living around us. This research was conducted by students of the UNNES Postgraduate Chemistry Education Magister Program. The process for water treatment employedthepotentialnaturalcoagulantofmoringaseedextractusinganEthno-STEM approach.Thisresearchwascarriedoutasachemicalprojecttask,namelytheproject of using potential bio-coagulant of Moringa oleifera seeds or Moringa plant. In this study, tests were carried out on the use of bio coagulant of moringa seeds extract with various varieties to purify turbid water. The research results concluded that the magisters of chemistry education have been able to design and implement the integrated Ethno-STEM chemical project learning on water purification topic using moringa seed extract (Maringo oleifera). In addition, the findings indicated that the studentswereabletoreconstructethnical-basedscientificknowledgeinthecontextof STEM;andwaterpurificationexperimentswithbio-coagulantofMoringaseedextracts.


Background: Avascular Necrosis / Osteonecrosis of the femoral head is a debilitating condition affecting the hip joint and is one of the most common causes of total hip replacement. The available treatments include pharmacological and surgical options with Total hip arthroplasty (THA) being the mainstay of treatment. We here is studying a novel technique of combining micro core decompression with intra-lesional bisphosphonate as a treatment for osteonecrosis of the hip. Materials and Methods: A prospective study of 19 hips was done. There were 11 males and 4 females ranging 42 - 63 years. Four hips were stage I, ten hips were stage IIA, three hips were stage IIb and two hips were stage III. 16 hips (40%) had stage IIb and 24 hips (60%) had stage III ONFH. The minimum period of follow up was 24 months. All patients were assessed according to the Harris Hip Score (HHS). The operative procedure include decompressing the avascular area with drilling then injecting the zoledronic acid locally. Results: The mean preoperative modified Harris Hip Score in stage I (n=4), stage IIa (n=10), stage IIb (n=3) and Stage III (n=2) were 81.9, 72.7, 68.8 and 59.2 respectively. The mean postoperative modified Harris Hip Score at two years in stage I, stage IIa, stage IIb and Stage III were 97.3, 91.1, 88.4 and 82.5 respectively. Conclusion: We found that the use of micro core-decompression with intra-lesional bisphosphonate will provide higher chances towards hip preservation especially in late cases or cases with larger lesions where core decompression may not be successful.


Attitudes are evaluative statements ― either favorable or unfavorable ― concerning objects, people or events. Attitude, which consists of cognitive, affective and behavioral components, reflects how one feels about something. New product includes new-to-the-world products, exiting products that are targeted to new markets or market segments, improvements and revisions of existing products, and so on. The article depicts an empirical study in which 200 consumers who lived in Dhaka City were asked about their attitudes toward vacuum cleaners and rice cookers, which have been selected as new products for this study. Vacuum cleaners and rice cookers are new products in the sense that they are existing products targeted at new market (Bangladesh). The principal findings of this study are that consumers of Dhaka City have a weakly positive attitude toward vacuum cleaners and rice cookers. In addition, age, gender, education, marital status, and family income influence the nature of consumers' attitudes toward vacuum cleaners and rice cookers as new products. But occupation does not always influence consumer attitude toward rice cookers as a new product.


Worley and Mohram (2014) state that academics are yet to provide frameworks to handle the rapidly changing market environment, and because technology is often instrumental in the change process now, the traditional change models are less relevant and out of date. Therefore, this research sets out to evaluate the process and techniques used to manage change in large organisations, in this case in the casual dining industry, using Mitchells and Butlers PLC as a case study. The literature highlighted how important different components are to making change initiatives successful. Adopting an interpretivist philosophy and using qualitative research methods, the questions posed were shaped by the themes emerging from the literature. By interviewing managers and conducting focus groups for employees, the key findings helped meet the aim and objectives of this study. The findings of the research support the majority of change management theories but it established that the components of change management model are often considered by managers but rarely shape what happens in practice. This research project has revealed that change management in practice involves effectively planning and coordinating the people and resources of an organisation but these needs to be adaptable. In addition, establishing desirable objectives that are sufficiently explored, planned, communicated and executed will be beneficial to the organisation. The findings did however establish that the post-change environment was exceptionally important to ensure the change was sustained in the organisation but although expert support and training is suggested to achieve this, further research in this area would benefit future change initiatives.


We previously discovered a cellular isoform of titin (originally named T-protein) colocalized with myosin II in the terminal web domain of the chicken intestinal epithelial cell brush border cytoskeleton (Eilertsen, K.J., and T.C.S. Keller. 1992. J. Cell Biol. 119:549-557). Here, we demonstrate that cellular titin also colocalizes with myosin II filaments in stress fibers and organizes a similar array of myosin II filaments in vitro. To investigate interactions between cellular titin and myosin in vitro, we purified both proteins from isolated intestinal epithelial cell brush borders by a combination of gel filtration and hydroxyapatite column chromatography. Electron microscopy of brush border myosin bipolar filaments assembled in the presence and absence of cellular titin revealed a cellular titin- dependent side-by-side and end-to-end alignment of the filaments into highly ordered arrays. Immunogold labeling confirmed cellular titin association with the filament arrays. Under similar assembly conditions, purified chicken pectoralis muscle titin formed much less regular aggregates of muscle myosin bipolar filaments. Sucrose density gradient analyses of both cellular and muscle titin-myosin supramolecular arrays demonstrated that the cellular titin and myosin isoforms coassembled with a myosin/titin ratio of approximately 25:1, whereas the muscle isoforms coassembled with a myosin:titin ratio of approximately 38:1. No coassembly aggregates were found when cellular myosin was assembled in the presence of muscle titin or when muscle myosin was assembled in the presence of cellular titin. Our results demonstrate that cellular titin can organize an isoform-specific association of myosin II bipolar filaments and support the possibility that cellular titin is a key organizing component of the brush border and other myosin II-containing cytoskeletal structures including stress fibers.


The color histogram is a tool that has been widely used in many image processing and computer vision applications such as image retrieval and image segmentation. In these applications, the features in the color histogram are used as signatures for feature comparison, scene analysis and object recognition. Various histogram features were explained previously by several models in computer vision which incorporate the physical process of light reflection. However, most of these approaches are mainly based on a dichromatic reflectance model, and only consider the lighting coming directly from the light source in the scene. In this dissertation, we present a comprehensive study of the formation of color histogram structures based on both the theory and simulation of light reflection and transport in the three dimensional world with the full spectrum of visible light by using advanced computer graphic techniques. By using a physically accurate, precisely controlled computer graphic environment, we have been able to successfully isolate and reproduce the features in the color histogram observed by previous researchers. Furthermore, we have also produced more complex new features, such as off-plane thickening and "banana" shaped structures in the color histogram by incorporating global illumination in our image synthesis procedure. Several physically based reflectance models are used to illustrate and explain the formation of these features in the color histogram.
We then use the color histogram analysis techniques in a digital photographic application to extract the spectral information about the illumination in the scene and spectral information about the diffuse component of the reflectance of a dichromatic surface. This spectral information is then used to predict the appearance of objects in the image under different illumination spectra. Our method is demonstrated to show improved performance over some traditional illumination compensation methods, and has great potential in digital photography.


We examine how reducing subsidies for federal crop insurance affects the risk management portfolios of US soybean producers. We apply the portfolio optimization approach of Das and Statman \citeyearpar{das2013options} to model how producers' risk management portfolios change as subsidies for federal crop insurance premiums change, and examine how the changes to the risk management portfolios impact farmers' on-farm income and exposure to downside risk. We optimize farmers' risk management portfolio by adjusting the budget shares dedicated to each of four risk management tools: returns on production, forward contracting, savings, and crop insurance.


Controller Area Network is the most frequently used in-vehicle communication system in the automotive industry today. The communication inside the Controller Area Network (CAN) bus is typically encoded using proprietary formats in order to prevent easy access to the information exchanged on the bus. However, it is still possible to decode this information through reverse engineering, performed either manually or via automated tools. Existing automated CAN bus reverse engineering methods are still time-consuming and require some manual effort, i.e., to inject diagnostic messages in order to trigger specific responses. In this paper, we propose CANMatch – a fully automated CAN bus reverse engineering framework that does not require any manual effort and significantly decreases the execution time by exploiting the reuse of CAN frames across different vehicle models. We evaluate the proposed solution on a dataset of CAN logs, or traces, related to 479 vehicles from 29 different automotive manufacturers, demonstrating its improved performance with respect to the state of the art.


Wide bandgap materials are important in the organic optoelectronic field. In this study, a diphenylphosphine oxide-functionalized tetraphenylsilane moiety was designed and applied in the construction of wide bandgap materials. The wide bandgap polymer PFSCPO was synthesized via a Suzuki coupling reaction between diphenylphosphine oxide substituted tetraphenylsilane and carbazole modified dihexylfluorene. PFSC without the diphenylphosphine oxide group was also prepared for comparison. They both show high thermal stabilities and good morphological stabilities. Doped films using these two polymers as hosts and Ir(ppy)3 as a guest were prepared via the spin-coating method. Compared with PFSC, the diphenylphosphine oxide group with strong electron-withdrawing property decreased the LUMO energy level of PFSCPO and facilitated electron injection in OLEDs. The turn-on voltage was 7.5 V in the PFSC/Ir(ppy)3 doped device, which reduced to 6.3 V in the PFSCPO/Ir(ppy)3 doped device. The maximum current efficiency also increased from 8.83 cd A−1 to 9.33 cd A−1.


This study investigated the mental health implications of a service-learning partnership between therapeutic recreation (TR) college students and children/youth in a recreation inclusion program. Twenty-five TR students participated in 6-week inclusion program with a child/ youth partner with or without a disability. Resiliency results exhibited a directional increase (d<=.10) with three subscales significant in change for student's ability to deal with: whatever comes my way (p < .029), seeing the humorous side of things (p < .035), and coping with stress (p < .029). Further analysis found significance that males (p = .045) and racial/ethnic minority participants (p = .021.) had reduced their stress scores. Enjoyment scores significantly increased (p < .001). Analysis of reflection notes revealed two main themes: (1) emotional contagion, and (2) reducing stress and anxiety. These themes relate to key aspects of resilience, which demonstrates the value of service-learning for TR college students and the therapeutic potential for mental health support. Practice and research implications of service learning for TR are presented. Subscribe to TRJ


Since 1957, the European Union (EU) has been a constant and reliable partner of Latin America, on the one hand, and the Caribbean, on the other. It still offers a unique model of idealist interregionalism based on the promotion of its own integration model, combined with limited economic interests, soft power and, more recently, shared global visions such as sustainable development, Compared with the two bigger external actors, the United States and China, the EU is a normative actor that complements and sometimes counterbalances (in the cases of Brazil, Cuba, and Mexico) relations with the dominant power. Although, in relative terms, trade exchanges have declined since the 1990s, Latin America and the EU share a solid network of multilevel and contractual relations integrated by political dialogue, development cooperation, and investment flows. The EU signed free trade agreements plus (dialogue and cooperation) with Chile, Colombia, Ecuador, Mexico, Peru, the Caribbean, and Central America. In June 2019 finalized a twenty year process of free trade negotiations between the EU and MERCOSUR. Once in force and approved by EU institutions and the four South American states, the EU-MERCOSUR association agreement will reactivate trade exchange grounded on economic, political, social and cultural cooperation between state and non-state actors. Nonetheless, it remains unclear if the 32 states involved in the mixed agreement (European Commission's exclusive trade competences plus EU member states) will approve the deal in a foreseeable future.


A kinetic theory is used to find the dispersion relation of a plasma-loaded free-electron laser that takes into account the velocity spread of both beam and plasma electrons. For the weak-coupling regime, the dispersion relation for a cold electron beam and plasma is obtained and is studied numerically. The kinetic theory predicts that, for the cold beam and plasma, plasma density increases the growth rate of the higher-frequency resonance and lowers it for the lower-frequency resonance up to a certain plasma density. By increasing the plasma density further, a critical density will be reached that diminishes the instability.


HIV self-testing (HIVST) may play a role in addressing gaps in HIV testing coverage and as an entry point for HIV prevention services by empowering individuals to test themselves and reducing stigma-related barriers to HIV testing. We evaluated two health systems delivery approaches for HIVST distribution compared to referral to standard testing among female sex workers in Zambia. Trained peer educators in Kapiri, Chirundu, and Livingstone, Zambia each recruited 6 FSW participants. Peer educator-FSW groups were randomized to one of three arms: 1) delivery (direct distribution of an oral HIVST from the peer educator), 2) coupon (a coupon for collection of an oral HIVST from a health clinic/pharmacy), or 3) standard-of-care HIV testing. Participants in the two HIVST arms received two kits: one at baseline and one at three months. The primary outcome was any self-reported HIV testing in the past month at the one- and four-month visits, as HIV self-testing can replace other parts of HIV testing. Secondary endpoints included linkage to care, HIVST use in the intervention arms, adverse events, empowerment, sexual behaviors, and measures of stigma. Participants completed questionnaires at one and four months following peer educator interventions.965 participants were enrolled (delivery: N=322, coupon, N=323, standard, N=320); 20% had never tested for HIV. Overall HIV testing at one month was 94.9% in the delivery arm, 84.4% coupon, and 88.5% standard-of-care. Four month rates were 84.1% delivery, 79.8% coupon and 75.1% standard. HIV self-test use was higher in the delivery arm compared to the coupon arm (RR=1.14, 95% CI 1.05–1.23, P=0.001) at one month but there was no difference in at four months. Among participants reporting a positive HIV test at one (N=144) and four months (N=235), linkage to care was non-significantly lower in the two HIVST arms compared to the standard-of-care arms. At four months, participants reported significantly fewer clients per night in the delivery arm (mean difference -0.78 clients, 95% CI -1.28 to -0.28, P=0.002) and the coupon arm (-0.71, 95% CI -1.21 to -0.21, P=0.005) compared to standard-of-care. HIV self-testing coverage was high in all arms, suggesting that HIV self-testing is able to overcome stigma-related barriers to HIV testing in this population. Disclosure No significant relationships.


The aim of this article was to find potential connection between positive experiences from ICT training courses gained by teachers and multipliers and their ability to affect elderly people"s willingness to learn ICT skills and motivate them for future participation in ICT training courses through motivational workshops. Within the study the authors focus on the evaluation of the ICT training courses for teachers and multipliers and the motivational workshops for the elderly. The data obtained was quantitative and analyzed using SPSS software. The authors found a significant correlation between the number of possibilities for discussion provided during the ICT training courses for teachers and multipliers and the opinion that, from an overall perspective, the course helped the participants to be more sensitized to intergenerational issues and so understand the elderly people better. Similarly, the authors found significant correlation between the number of discussion possibilities during the motivational workshops for elderly and the level of interest in participation in future ICT training courses. The study showed that individuals who work in a teaching/learning process with elderly people need to be properly trained to be able to transfer knowledge and motivation to the elderly. Motivational workshops for the elderly should focus on individualized


In vitro experiments on 72 E. coli strains showed the presence of relationship between the level of their antilysozyme activity and a number of parameters of the reproduction of these bacteria. The factor analysis revealed the integration of the antilysozyme sign with the factors which determined the inhibition of the development of bacterial populations at early stages and controlled the accumulation of bacterial biomass. The study established that the beginning of the expression of the antilysozyme sign of E. coli was associated with the transition of the culture to the phase of slow growth, and the subsequent dynamics of the level of antilysozyme activity was only partially linked with the increase of biomass. The suggestion was made that the antilysozyme factor was one of the elements of the intracellular system regulating the synthesis (and/or stabilization) of peptidoglycan of bacterial cell walls.


Peer-to-peer (P2P) networks have been adopted for Internet live video-streaming service, and several practical systems have been deployed in past years due to the inherent scalability and ease of deployment. However, most of these systems are commercial and proprietary, and hence little research was done in the area of characterizing practical system performance properties. In this article, we mainly present our experience on a practical P2P-based live video- streaming system called GridMedia, which was employed to broadcast live the Chinese Spring Festival Gala show over the Internet. Benefiting from two sets of flush-crowd traces with about 15,239 and 224,453 concurrent users in a 300 kb/s streaming session in 2005 and 2006, we perform a trace study to understand the service capacity, quality of streaming service, connection heterogeneity, user geographic distribution, and request and online duration characteristics. Our observations shed light on those systems and further improvements in the arena of large-scale live video-streaming service over the Internet.


Colloidal clusters are prepared by assembling positively charged cross-linked polystyrene (PS) particles onto negatively charged liquid cores of swollen polymer particles. PS particles at the interface of the liquid core are closely packed around the core due to interfacial wetting. Then, by evaporating solvent in the liquid cores, polymers in the cores are solidified and the clusters are cemented. As the swelling ratio of PS cores increases, cores at the center of colloidal clusters are exposed, forming patchy colloidal clusters. Finally, by density gradient centrifugation, high-purity symmetric colloidal clusters are obtained. When silica-PS core-shell particles are swollen and serve as the liquid cores, hybrid colloidal clusters are obtained in which each silica nanoparticle is relocated to the liquid core interface during the swelling-deswelling process breaking symmetry in colloidal clusters as the silica nanoparticle in the core is comparable in size with the PS particle in the shell. The configuration of colloidal clusters is determined once the number of particles around the liquid core is given, which depends on the size ratio of the liquid core and shell particle. Since hybrid clusters are heavier than PS particles, they can be purified using centrifugation.


This study assessed the effect of other safety gear worn in proximity on the attenuation afforded by earmuffs attached to a hard hat. Seventy-two males and females participated: 24 under the age of 40 years with normal hearing, and 48 over the age of 40 years, half with normal hearing and half with bilateral high-tone hearing loss. Measurements were made with the ears unoccluded, with the muffs on hard hat alone, and with the muffs on hard hat in combination with safety glasses, an air-purifying half mask respirator or both glasses and respirator. They included (1) diffuse field hearing thresholds from 0.25-8 kHz, and (2) consonant discrimination in quiet and in 80-dB SPL speech spectrum noise. Attenuation was derived by subtracting the unoccluded from the protected hearing threshold at each frequency. Muff attenuation was within 6 dB of the manufacturer's specifications but decreased by as much as 5 dB when the glasses or respirator were worn and by 9 dB with both these devices. Males achieved 3 dB higher attenuation than females. However, hearing status had no effect. Consonant discrimination was significantly worse in noise. The impaired subjects performed more poorly when wearing the muff on hard hat but there was no additional effect of wearing the glasses and/or respirator. These results demonstrate that wearing other protective safety gear around the head can interfere with the hearing protection provided by earmuffs. They also confirm that for people with a hearing loss, the use of earmuffs may increase the communication handicap.


In cyanobacteria, the photosynthetic prokaryotes, direct interaction between photosynthesis and respiration exists at plastoquinone (PQ) pool, which is shared by the two electron transport chains. Another possible point of intersection of the two electron transport chains is NADPH, which is the major electron donor to the respiratory chain as well as the final product of the photosynthetic chain. Here, we showed that the redox state of NADPH in the dark affected chlorophyll fluorescence induction in the cyanobacterium Synechocystis sp. PCC 6803 in a quantitative manner. Accumulation of the reduced NADPH in the dark due to the defect in type 1 NAD(P)H dehydrogenase complex in the respiratory chain resulted in the faster rise to the peak in the dark-to-light induction of chlorophyll fluorescence, while depletion of NADPH due to the defect in pentose phosphate pathway resulted in the delayed appearance of the initial peak in the induction kinetics. There was a strong correlation between the dark level of NADPH determined by its fluorescence and the peak position of the induction kinetics of chlorophyll fluorescence. These results indicate that photosynthesis interacts with respiration through NADPH, which enable us to monitor the redox condition of the acceptor side of photosystem I by simple measurements of chlorophyll fluorescence induction in cyanobacteria.


An increasing number of field examples in mountain belts show that the formation of passive margins during extreme continent thinning may occur under conditions of high to very high thermal gradient beneath a thin cover of syn-rift sediments. Orogenic belts resulting from the tectonic inversion of distal margins and regions of exhumed continental mantle may exhibit high-temperature, low-pressure (HT-LP) metamorphism and coeval syn-extensional, ductile deformation. Recent studies have shown that the northern flank of the Pyrenean belt, especially the North Pyrenean Zone, is one of the best examples of such inverted hot, passive margin. In this study, we provide a map of HT-LP metamorphism based on a data set of more than 100 peak-temperature estimates obtained using Raman spectroscopy of the carbona-ceous material (RSCM). This data set is completed by previous PT (pressure and temperature) estimates based on mineral assemblages, and new 40 Ar– 39 Ar (amphibole, micas) and U–Pb (titanite) ages from metamorphic and magmatic rocks of the North Pyrenean Zone. The implications on the geological evolution of the Cretaceous Pyrenean paleomar-gins are discussed. Ages range mainly from 110 to 90 Ma, and no westward or eastward propagation of the metamor-phism and magmatism can be clearly identified. In contrast, the new data reveal a progressive propagation of the thermal anomaly from the base to the surface of the continental crust. Focusing on the key localities of the Mauleon basin, Arguenos–Moncaup, Lherz, Boucheville and the Bas-Agly, we analyze the thermal conditions prevailing during the Cre-taceous crustal thinning. The results are synthetized into a series of three regional thematic maps and into two detailed maps of the Arguenos–Moncaup and Lherz areas. The results indicate a first-order control of the thermal gradient by the intensity of crustal thinning. The highest grades of metamor-phism are intimately associated with the areas where subcon-tinental mantle rocks have been unroofed or exhumed.


As Artificial Intelligence technologies are increasingly used to make important decisions and perform autonomous tasks, providing explanations to allow users and stakeholders to understand the AI has become a ubiquitous concern. Recently, a number of open-source toolkits are making the growing collection of Explainable AI (XAI) techniques accessible for researchers and practitioners to incorporate explanation features in AI systems. This course is open to anyone interested in implementing, designing and researching on the topic, aiming to provide an overview on the technical and design methods for XAI, as well as hands-on experience with an XAI toolkit.


For Origen, the purpose of reading the Scriptures is to be transformed more and more into the likeness of God, who is Love, through the Logos embodied in the Scriptures. This article first situated Origen's approach to the Scriptures in the broad agreement over the centuries that the Scriptures are meant to address the present readers and not merely the original readers. This has led to various approaches to actualise the text up to the present varieties of contextual exegesis. Secondly, the article showed how, for Origen, the aim of actualising the text is the transformation of the readers. It will be necessary, therefore, to briefly present some of the key aspects of Origen's pre-understanding. The third part focused on Origen's understanding of the reading process as a movement from the letter to the spirit, a process that involves the transformation of the reader. This process is a struggle to understand what love, which is both the mystery of God and the aim for which every being is created through the Logos, is.


The Rizzoli Quadrifolio art series combines the most popular artists with authoritative text and a fresh, unique format destined to appeal to children and adults alike. Featuring sixteen pages that open up to four times the individual page size, this series allows the reader to delve into the details of individual paintings or see the full horizontal development of a fresco. With stunning color reproductions, expert commentary, and a revolutionary format, Rizzoli Quadrifolios is a pioneering art series.Following the success of Michelangelo, the Sistine Chapel; Vincent van Gogh; Gustav Klimt; and Caravaggio, is Leonardo da Vinci: The Last Supper, a book dedicated to perhaps one of the most significant and recognizable works of art ever created. The reader is afforded extraordinary details of this restored but still deteriorating fresco, perhaps the Renaissance master's most important work. Located in a small monastery in Milan, the work has recently been restored so that the delicate faces which register, with great subtlety, the gravity of the moment at which Christ announces to his apostles that one among them will betray him, are visible once again. Every inch of the work is reproduced here in illuminating close-ups so that the masterpiece can be appreciated anew.


The X-ray crystal structure of Torpedo californica acetylcholinesterase (TcAChE) complexed with BW284C51 [CO[-CH(2)CH(2)-pC(6)H(4)-N(CH(3))(2)(CH(2)-CH=CH(2))](2)] is described and compared with the complexes of two other active-site gorge-spanning inhibitors, decamethonium and E2020. The inhibitor was soaked into TcAChE crystals in the trigonal space group P3(1)21, yielding a complex which diffracted to 2.85 A resolution. The structure was refined to an R factor of 19.0% and an R(free) of 23.4%; the final model contains the protein, inhibitor, 132 water molecules and three carbohydrate moieties. BW284C51 binds similarly to decamethonium and E2020, with its two phenyl and quaternary amino end-groups complexed to Trp84 in the catalytic site and to Trp279 in the peripheral binding site, and its central carbonyl group hydrogen bonded very weakly to Tyr121. Possible reasons for decamethonium's weaker binding are considered. The relative strength of binding of bisquaternary inhibitors to acetylcholinesterase and the effect of several mutations of the enzyme are discussed in the context of the respective X-ray structures of their complexes with the enzyme.


ABSTRACT Purpose: To compare heme oxygenase 2 (HO-2) enzyme levels detected by immunohistochemical staining methods in the cornea epithelium obtained from keratoconus patients and normal subjects. Materials and Methods: The keratoconus group included 69 eyes of 69 patients with keratoconus scheduled for cross-linking surgery. The control group included 52 eyes of 52 patients with refractive error scheduled for photorefractive keratectomy surgery. After a detailed ophthalmologic examination, corneal topographic maps of each patient were generated, and then the patients underwent surgery. The corneal epithelium was collected mechanically during the surgery, fixed with formalin, embedded in paraffin blocks, and sectioned by microtomes. HO-2 antibodies were applied to the samples for immunohistochemical evaluation. The intensity of the staining was identified as negative, weak, moderate or strong. The keratoconus group was classified as early (average keratometry (AvrK) ≤ 47 D), moderate (AvrK 47–55 D) and advanced keratoconus (AvrK ≥ 55 D). Finally, intergroup and intragroup comparison analyses were made statistically. Results: In the keratoconus group, 20 (29%) (14 weak and 6 moderate staining) of the 69 corneal epithelial specimens were identified with HO-2 expression. In the control group, 40 (76.9%) (16 moderate and 24 strong staining) of the 52 corneal epithelial specimens were identified with HO-2 expression. HO-2 expression in the corneal epithelial specimens was significantly less in the keratoconus group than in the control group (p < 0.001). There was no substantial difference among the keratoconus subgroups in terms of staining with the HO-2 antibody (p = 0.797). Conclusions: The HO-2 enzyme staining using immunohistochemical methods was at lower amounts in the keratoconic corneal epithelial cells as compared with normal corneal epithelial cells. The HO-2 enzyme may play a role in the etiopathogenesis of keratoconus.


type="main"> Most treatments of territorial rights include a discussion (and rejection) of Locke. There is a remarkable consensus about what Locke's views were. For him, states obtain territorial rights as the result of partial transfers of people's property rights. In this article, I reject this reading. I argue that (a) for Locke, transfers of property rights were neither necessary nor sufficient for territorial rights and that (b) Locke in fact held a two-part theory of territorial rights. I support this reading by appealing to textual and contextual evidence. I conclude by drawing a lesson from Locke's views for current debates on territorial rights.


The contribution of chemical processes to the erosion of beachrocks and aeolianites within the intertidal zone has long been a contentious issue. This paper briefly summarises previous work and describes new observations from the southeast coast of southern Africa. Field observations of isolated seawater bodies on the intertidal platform established a range of pH values, ascribed to diurnal variation. The contribution of biochemical processes to chemical erosion of beachrock is highlighted. Seventeen different erosive features occurring in coastal outcrops of beachrocks and aeolianites are described and illustrated. The majority of these erosional features occur on intertidal outcrops of beachrock/aeolianite, making a crude zonation of the topography possible. The physical dimensions and spatial distribution of erosional features within the intertidal and supratidal zones are described. Processes responsible for the formation of the erosional features include: physical erosion: chemical erosion; bioerosion; bioarmouring and algal induration. The possible modes of formation of each of the erosional features is discussed. Three different types of intertidal platforms occur on this coast: (1) Type 1 intertidal platforms comprise beachrock or aeolianite, sculpted by the retreat of a sea-level notch into a rocky headland; (2) Type 2 intertidal platforms comprise planed surfaces of beachrock or aeolianite which extend landwards under a cover of beach sand; (3) Type 3 intertidal platforms comprise multiple layers of seaward dipping beachrock which are preferentially eroded into a stepped appearance.


Summary form only given. For wide-angle scanning planar arrays, the magnitude of the reflection coefficient may change substantially with scan angle, scan plane and wave polarization. The conventional solution to this problem consists in the use of wide-angle impedance matching (WAIM) structures made up of a stack of dielectric layers. Much greater flexibility may be achieved by employing anisotropic slabs with controllable spatial dispersivity. Artificially structured materials (or metamaterials) make this approach feasible by allowing the simultaneous control of dielectric and magnetic properties in the different directions (S.Sajuyigb et al., IET Microw. Antennas Propag., 4(8), 1063-1072, 2010).


Objective: Supplementation with tetrahydrobiopterin, a nitric oxide synthase cofactor, may reduce microvascular endothelial dysfunction in severe sepsis. We studied whether tetrahydrobiopterin administration exerts beneficial effects in an ovine septic shock model. Design: Randomized animal study. Setting: University hospital animal research laboratory. Subjects: Fourteen adult female sheep. Interventions: Fecal peritonitis was induced, and the sheep were randomized to receive tetrahydrobiopterin (n = 7), given intravenously as 20mg/kg boluses at 4 and 12 hrs after sepsis induction, or placebo (n = 7). All animals were fluid resuscitated. The experiment was continued until death or for a maximum of 30 hrs. Measurements and Main Results: In addition to standard hemodynamic assessment, the sublingual microcirculation was evaluated using sidestream dark-field videomicroscopy. The first bolus of tetrahydrobiopterin blunted the increase in heart rate and cardiac index seen in the control group without affecting mean arterial pressure, and the second bolus of tetrahydrobiopterin prevented the decreases in cardiac index and mean arterial pressure. The reduction in mixed venous blood oxygen saturation and the increase in blood lactate seen in the control group were also delayed. Tetrahydrobiopterin significantly attenuated the deterioration in perfused small vessel proportion and density, microvascular flow index, and the increase in microvascular heterogeneity observed in the control group. Tetrahydrobiopterin was associated with better preserved lung compliance and PaO2/FIO2 ratio, which were associated with a lower lung wet/dry weight ratio at the end of the study. Median survival time was significantly prolonged in the tetrahydrobiopterin group (25.0 vs. 17.8 hrs, p < .01). Conclusion: In this clinically relevant model of sepsis, tetrahydrobiopterin supplementation attenuated the impairment in sublingual microvascular perfusion and permeability, which was accompanied by better preserved gas exchange, renal flow and urine output, and prolonged survival.


The envisaged dual system of vocational education and training in South A frica : assessing the potential thereof from a comparative perspective.
he aim of this research was to assess the potential of the envisaged dual system of vocational education and training in South Africa from a comparative perspective, namely, the German prototype and the many attempts to transplant this to other countries. The dual system in Germany is outlined and assessed, followed by an evaluation of attempts to export it to other countries. Subsequently, the motivation for and details of the envisaged dual system in South Africa are discussed, before extrapolating, in the concluding section, the implications of the experience abroad for South Africa. The population dynamics, economy, the mobile employment market and low prestige accorded to vocational education do not bode well for a dual system in South Africa. On the other hand, building the qualifications attained in the dual system into the National Qualifications Framework, and empowering would-be learners from designated groups by means of the Equal Employment Act, could create a dual system that could be exemplary for other developing countries, and even for Germany.


Background : As the Government Hospital of East Java Province, Menur Mental Hospital provide inpatient main public services with tariff that set by the Director of the hospital. Status of Badan Layanan Umum Daerah (BLUD) requires hospitals to improve financial independence along with improved quality of service, so that the necessary cost analysis as the basis for calculating rates and cost efficiency in order to mak e the right and accurate decisions. Determination of the major inpatient services rates using Activity Based Costing will track activity based on those costs. Objective : Calculate the unit cost per class, analyze the activity and performance of financial independence of the main inpatient services. Methods : The study design applied in a descriptive cross-sectional field. Results : The unit cost per day of hospitalization after activity analysis, are: VIP 1 Rp1.264.940,29; VIP 2 Rp982.913,63; Main 1 Rp513.692,85; Main 2 Rp423.506,13, and Main 3 Rp282.026,07. Fixed cost are Rp1.490.013.692,04; while the variable cost per class are 1 VIP Rp257.777,48; VIP 2 Rp229.777,48; Main 1 Rp195.582,48; Main 2 Rp164.852,48; and Main 3 Rp126.125,33. Conclusion : Unit Cost of all classes of treatment before analysis of activity  are higher than current tariff. Non value-added activities cost are Rp341.235.192,80; so that the unit cost of each class is reduced by an average 9.25% when including the salaries of civil servants, and 12.47% without the salaries of civil servants. Level of financial independence after the analysis of activity increased to 94.88%  from 80,00% if the salaries of civil servants still subsidized by the government. Suggestion : Keep the understanding and commitment, especially in cost efficiency through further analysis of activities. If civil servants salaries are not subsidizied anymore, Main 2 and Main 3 class are not able to reach the Break Even Point (BEP), although with Bed Occupancy Rate (BOR) to be considered for a 100% rate increase. Keywords : Activity Based Costing, financial independence, hospital


This study investigates the manner in which labour market flexibilisation is linked to the incorporation of Brazilian immigrants and their prospects for upward mobility in Japan. Although earlier studies have documented these relationships in North America and Europe, little is known about the socio-economic circumstances and recent changes in institutional settings in several Asian countries that currently accept a large number of immigrants. The results of this study indicate that the human and social capital of Brazilian immigrants has played a minor role in helping them to obtain standard employment. The highly regulated labour market in Japan has hindered the efforts of Brazilian immigrants to gain access to 'good' jobs with stable employment prospects, regardless of the degree of human and social capital that is possessed by individual immigrants. In addition, the recent increase in labour market flexibility has rendered it exponentially more difficult for Brazilian immigrants to enter the core employment sector. These institutional conditions for Brazilian immigrants have shaped the mechanisms of their integration and thereby prevented them from achieving upward mobility in Japanese society. These findings also reflect a lack of public debate and institutional support for the integration of immigrants into the wider Japanese society.


Cancer is characterized by uncontrolled growth or proliferation of cells. Besides conventional cancer therapy, antibodies can be used to target tumor-related molecules like the epidermal growth factor receptor (EGFR) and the hepatocyte growth factor (HGF) receptor (Met). Unfortunately, this attenuates tumor growth instead of eliminating tumors completely. Improvement can be made by using so-called antibody-drug conjugates (ADC) that combine the tumor-specificity of antibodies with the cytotoxicity of therapeutic agents. The variable domain of the heavy chain of heavy chain only antibodies (VHH or nanobody) are small antibody fragments that display high binding affinity in combination with good tumor penetration. This thesis provides a detailed overview of the use of nanobodies in cancer-therapy. Nanobodies for the delivery of therapeutic molecules are referred to as Nanobullets. Because Nanobullets often act on intracellular processes, they should facilitate both tumor targeting and intracellular delivery. Therefore, a proper understanding on cellular uptake by tumor cells is important. Ligand-induced signaling of both EGFR and Met is silenced by a negative-feedback mechanism consisting of rapid internalization and subsequent degradation of the receptor-ligand complex. This process is mediated by ligand-induced post-translational modifications like phosphorylation, ubiquitination and acetylation. Recently, ligand-induced clustering of EGFR on the plasma membrane was also found to be involved in receptor internalization. In this thesis, the mechanism behind clustering-induced endocytosis of EGFR was studied in more detail. EGFR clustering induces kinase-independent, clathrin-mediated endocytosis (CIC-ME), which is followed by an unconventional, ubiquitin-independent trafficking towards lysosomal degradation. CIC-ME of EGFR requires a previously unrecognized role for the transmembrane dimerization motifs in receptor internalization. Subsequently, this knowledge was put to practice by developing different examples of Nanobullets for intracellular drug delivery. Nanobody-decorated, albumin-based nanoparticles (NANAPs) facilitated the intracellular release of the platinum-linked multikinase inhibitor 17864-Lx in the lysosomes of EGFR-expressing tumor cells. Similarly, anti-Met NANAPs constitute a novel type of biomaterial for lysosomal drug delivery in Met-expressing tumor cells. Finally, nanobody-photosensitizer (PS) conjugates against EGFR exhibited specific and strong cytotoxicity, which could be improved by intracellular delivery of the PS via CIC-ME (100% specific cell death, IC50 of ~1nM). The small size, high specificity and high potency of these Nanobullets make them promising candidates for further in vivo testing.


We present tentative evidence for the existence of a dissolved star cluster at [Fe/H] = −2.7 in the Sextans dwarf spheroidal galaxy. We use the technique of chemical tagging to identify stars that are highly clustered in a multi-dimensional chemical abundance space (-space). In a sample of six stars, three, possibly four, stars are identified as potential cluster stars. The initial stellar mass of the parent cluster is estimated from two independent observations to be , assuming a Salpeter (Kroupa) initial mass function. If corroborated by follow-up spectroscopy, this star cluster is the most metal-poor system identified to date. Chemical signatures of remnant clusters in dwarf galaxies like Sextans provide us with a very powerful probe to the high-redshift universe. From available observational data, we argue that the average star cluster mass in the majority of the newly discovered ultra-faint dwarf galaxies was notably lower than it is in the Galaxy today and possibly lower than in the more luminous, classical dwarf spheroidal galaxies. Furthermore, the mean cumulative metallicity function of the dwarf spheroidals falls below that of the ultra-faints, which increases with increasing metallicity as predicted from our stochastic chemical evolution model. These two findings, together with a possible difference in the 〈[Mg/Fe]〉 ratio suggest that the ultra-faint dwarf galaxy population, or a significant fraction thereof, and the dwarf spheroidal population were formed in different environments and would thus be distinct in origin.


The work deals with the Particle in Cell/Monte Carlo Collision (PIC/MCC) analysis of the problem of detection and identification of impurities in the nonlocal plasma of gas discharge using the Plasma Electron Spectroscopy (PLES) method. For this purpose, 1d3v PIC/MCC code for numerical simulation of glow discharge with nonlocal electron energy distribution function is developed. The elastic, excitation, and ionization collisions between electron-neutral pairs and isotropic scattering and charge exchange collisions between ion-neutral pairs and Penning ionizations are taken into account. Applicability of the numerical code is verified under the Radio-Frequency capacitively coupled discharge conditions. The efficiency of the code is increased by its parallelization using Open Message Passing Interface. As a demonstration of the PLES method, parallel PIC/MCC code is applied to the direct current glow discharge in helium doped with a small amount of argon. Numerical results are consistent with the theoretical...


Surface modification of zinc oxide nanoparticles (ZnO NPs) is a strategy to tune their biocompatibility. Herein we report on the synthesis of a series of fluorescent ZnO NPs modified with 2-10% (3-glycidyloxypropyl)trimethoxysilane (GPTMS) to investigate the fluorescence properties and to explore their applications in microbiology and biomedicine. The obtained ZnO NPs were characterized by X-ray diffraction (XRD), high resolution transmission electron microscopy (HRTEM) and Fourier transform infrared spectroscopy (FTIR). Size reduction occurred from ca. 13 nm in unmodified ZnO to 3-4 nm in silane-modified samples and fluorescence spectra showed size-dependent variation of the photoemission bands' intensity. The antibacterial and cytotoxic activities were investigated on Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria, and in ovarian (A2780) and prostate (PC3) cancer cells by tetrazolium/formazan-based methods. The antibacterial effect was higher for E. coli than S. aureus, while the cytotoxic activity was similar for both cancer cells and varied with the particle size. Cell death by apoptosis, and/or necrosis versus autophagy, were explored by flow cytometry using an Annexin V based-method and transmission electron microscopy (TEM). The main mechanism of ZnO NPs toxicity may involve the generation of reactive oxygen species (ROS) and the induction of apoptosis or autophagy. This work revealed the potential utility of GPTMS-modified ZnO NPs in the treatment of bacterial infection and cancer.


This synthesis paper focuses specifically on the relationship between economic growth and the chronically poor. To what extent are the chronically poor able to participate in growth or from the benefits of growth? What factors enhance or restrict this ability? To what extent is growth accompanied by households falling back into poverty, and if so what processes underlie this? And what policy implications can be drawn out for governments and development partners?


Mammographic density is one of the strongest, independent risk factors in the development of breast cancer. Women with mammographically dense breasts, those with greater than or equal to 75% dense tissue, are at a four to six‐fold greater risk of developing breast cancer when compared to those with "no measurable dense tissue," in which the breasts are composed entirely of fat. Many of the established risk factors for breast cancer have been shown to be associated with variations in breast density (i.e., age, menopausal status, parity, BMI, and postmenopausal hormone use). Additionally, twin studies have also shown that heritability accounts for approximately 60% of the variance in mammographic density. Given the established role of estrogens in the development and progression of breast cancer, we have evaluated the role of 17 single‐nucleotide polymorphisms (SNPs) in the estrogen receptor 1 and 2 genes ( ESR1 and ESR2 ), and the recently identified G‐Protein Coupled Estrogen Receptor 1 ( GPER ) gene, which has been demonstrated to regulate physiologic responses to estrogens independent of the traditional estrogen receptors. This study population consisted of 370 cancer‐free (excluding cancers of the skin) Caucasian, postmenopausal women enrolled in the Mammograms and Masses Study (MAMS). Three different measures of mammographic density were computed: dense breast area, total breast area, and percent breast density, using the classification system developed by Wolfe in 1976, and a compensating polar planimeter, wax pencil, and transparent overlay. Breast density was calculated as the proportion of visibly dense breast to total breast area, expressed as a percentage. DNA was extracted from buffy coat samples, and genotyping was done using the Sequenom iPLEX Gold Assay. Heterozygote and homozygous variant genotypes were collapsed and compared to the common allele genotype for all statistical analyses. General linear models and χ 2 analyses were conducted. We arranged our percent density variable into tertiles for further analysis. We observed that three SNPs in ESR2 (rs12435857, rs1256044, and rs1256031) were significantly associated with percent mammographic density. For ESR2 rs1256044 and rs1256031, mean percent mammographic density was significantly higher among women with at least one rare allele compared to women homozygous for the common allele (respectively, P =0.02 and P =0.03). Conversely, mean percent mammographic density was significantly higher among women with ESR2 rs12435857 GG genotype compared to those with GA/AA genotypes, 29.0 and 23.7, respectively ( P =0.03). Our results suggest that common genetic variation in ESR2 is associated with percent mammographic density. Since estrogen receptor genes are highly expressed in breast tissue, functional SNPs in these genes may alter breast cancer risk, by altering mammographic density. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A2.


The aim of the study was to study the effect of constructive based training approach on teachers' attitude and students' achievement. The study comprised 80 students of class VI from Nagar Palika Girls Middle School Balmiki Basti New Delhi and Nagar Palika Girls Sr. Sec. School, Havelock Square, New Delhi. A quasi experimental pre-test and post-test design was applied in the present study. A pre and post -test design was applied on students and teachers learning and teaching Hindi subject. A training of 200 hours of constructive teaching training was given to one group of 15 teachers, whereas a conventional teaching training was given to another grou of 15 teachers. The training for both the groups was completed in 8 weeks.  After receiving the training both the groups used the approaches in their classes in which they had been trained. Therefore one group of students was taught the Hindi Subjects by using constructive approach where as another group was taught by using conventional approach of teaching. Teacher-made test with multiple-choice objective type questions was used to assess the learners' achievement in pre-test, and post-test was carried out just after two month of the experiment. Similarly teacher's attitude scale of S P Ahluwalia (1990) was administered before the training of teachers and also after completion of the training.The t values obtained revealed that constructivist method enhances the academic achievement and problem solving ability of the pupils. It was also found that both the group of teachers differs significantly on the teaching attitude. Keywords: Constructive based training approach, teachers' attitude and students achievement


Presently the automotive industry is facing enormous pressure due to global
competition and ever changing legislative, economic and customer demands. Both,
agility and reconfiguration are widely recognised as important attributes for
manufacturing systems to satisfy the needs of competitive global markets. To facilitate
and accommodate unforeseen business changes within the automotive industry, a new
proactive methodology is urgently required for the design, build, assembly and
reconfiguration of automation systems. There is also need for the promotion of new
technologies and engineering methods to enable true engineering concurrency between
product and process development. Virtual construction and testing of new automation
systems prior to build is now identified as a crucial requirement to enable system
verification and to allow the investigation of design alternatives prior to building and
testing physical systems. The main focus of this research was to design and develop
reconfigurable assembly systems within the powertrain sector of the automotive
industry by capturing and modelling relevant business and engineering processes.
This research has proposed and developed a more process-efficient and robust
automation system design, build and implementation approach via new engineering
services and a standard library of reusable mechanisms. Existing research at
Loughborough had created the basic technology for a component based approach to
automation. However, no research had been previously undertaken on the application of
this approach in a user engineering and business context. The objective of this research
was therefore to utilise this prototype method and associated engineering tools and to
devise novel business and engineering processes to enable the component-based
approach to be applied in industry. This new approach has been named Configurable
and Collaborative Automation Systems (CO AS). In particular this new research has
studied the implications of migration to a COAS approach in terms of I) necessary
changes to the end-users business processes, 2) potential to improve the robustness of
the resultant system and 3) potential for improved efficiency and greater collaboration
across the supply chain... cont'd


Daniel Kieffer's photographs constantly transport the viewer from one side of the lens to the other. With his camera at the service of sensation rather than the "beautiful image," Kieffer returns us to the essence of an art that teaches us about "the unconscious view" (Walter Benjamin). Seeing and experiencing sensation seem to be the conditions of artistic expression. The living soul is capable of anything. What can be expressed is made possible only under the guidance of sensation. Knowing things (learning) is not the only purpose of the art of seeing; this art also allows us to understand things and thus interpret the world better (become the other at the moment one encounters it). Through his witnessing, the photographer enables us to see the world from the outside (distance), but, through his involvement, he participates in what he witnesses (proximity); the result is a pragmatic, disturbing effect on our position with regard to the world and its representation. Excerpt of a text by Charles Perraton


Statement of the problem: Early detection of potentially malignant epithelial lesions (PMELs) is aimed at improving survival rates as carcinogenesis is a multistep process and prevention is possible if these lesions are detected at an early and reversible stage of the disease. Objectives: This prospective clinical study was designed to determine the prevalence of bilateral mirror-image PMELs in patients presenting with unilateral PMELs clinically. A modified brush biopsy technique was employed to detect early cytological epithelial changes if any, in the contralateral normal oral mucosa. Materials and method: Sixty individuals presenting with unilateral PMELs were selected for this study. These comprised 30 (50%) Indians, 24 (40%) Chinese, 5 (8.3%) Malays and one (1.7%) Nepalese. All selected cases had histopathological confirmation of their primary existing lesion(s) as inclusion criteria in this study. Cases which had subsequently presented with a lesion contralateral to the existing lesion were also subjected to scalpel incisional biopsy on this second lesion. The remaining cases which presented with a unilateral PMEL at the time of this clinical study were subjected to a brush biopsy on the clinically normal looking mucosa contralateral to the existing lesion. Results: A total of 70 lesions were detected in 60 patients. The most common PMEL found was oral lichen planus. Of the 60 patients studied, 26 exhibited mirror-image lesions either metachronously (73%) or synchronously (27%). The remaining cases that had undergone brush biopsy on the contralateral side to the existing PMEL yielded normal histological results. Conclusions: Present findings demonstrated that patients presenting with PMELs in the upper aerodigestive tract are at greater risk of developing a second lesion most probably on the contralateral mirror-image site. However the efficacy of brush biopsy method in detecting epithelial changes remained inconclusive due to the small sample examined.


Seabirds are long-lived, diverse and behaviourally complex marine top predators that are capable of traversing large areas of the global oceans. Consequently, this group are at risk from the wide and persistent range of anthropogenic activities working in this environment. Understanding the consistency with which individuals and populations use the marine environment over space and time, and the mechanisms underlying at-sea behaviour is therefore vital for interpreting population dynamics and developing appropriate and long-standing conservation strategies. This thesis utilises a combination of state-of-the-art tracking technologies and biogeochemical analyses to provide a better understanding of the at-sea movements, ecology and behaviour of a critically endangered seabird: the Balearic shearwater Puffinus mauretanicus. This species is the most threatened seabird in Europe and is undergoing continued population declines, believed to be largely associated with at-sea mortality from fisheries bycatch and predation on land. Despite intensive study during the breeding season, knowledge of the at-sea ecology of Balearic shearwaters during key phases of the annual cycle remains poor. Year-round tracking from colonies on the Balearic Islands yielded new insights into migration strategies of individuals and populations. Most individuals remained faithful to non-breeding areas over the course of the five-year study, although some plasticity in migration behaviour was also detected, indicating capacity for change. Patterns of differential migration were persistent in the main study population, and were linked to sex-based (and potential life stage-based) differences in migratory behaviour, which are most likely associated with varying ties to the breeding grounds. Links between reproductive performance and non-breeding behaviour were also detected, demonstrating an importance of carry-over effects in this species, with potential implications for population dynamics. Furthermore, behavioural differentiation was found between island populations. Migration strategies, use of foraging habitat and phenology differed between a potential Balearic/Yelkouan shearwater hybrid population on Menorca and a neighbouring colony of Balearic shearwaters on Mallorca, providing insights into the relatedness of Puffinus species in the Mediterranean, and emphasising the need to identify units for management that are both ecologically and evolutionarily relevant. Combined geolocation, isotope and feather moult data further identified use of a diversity of foraging tactics in northeast Atlantic waters, and spatial differences in non-breeding dietary behaviour. These findings implicate a role of both forage fish and fisheries in shaping patterns of at-sea distribution during the non-breeding season, and may prove useful for future assessment of seabird responses to anthropogenic and environmental change. During the breeding season, persistent use of highly productive coastal habitats was identified, indicating exploitation of predictable resources. Such movements emphasise the vulnerability of the Balearic shearwater to anthropogenic activity, but also highlight the potential of area-based management approaches for species protection, when combined with management of human activities throughout the species' distribution range. Together, the findings of this research provide urgently needed information on the at-sea behaviour and ecology of the Balearic shearwater, which should contribute to improved management efforts aimed at increasing population viability. In addition, this thesis contributes to a wider understanding of individual behaviours and inter-seasonal interactions in seabirds, and identifies the need to establish the movement behaviour of a wider range of life stages and populations across distinct seasons.


Class action law enforcement comprises a sequential, multi-stage investment opportunity under conditions of multi-dimensional uncertainty. This general proposition suggests that the myriad aspects of plaintiffs' attorneys' performance in the course of class action law enforcement can be treated and analyzed as sequential options to invest and sequential investment decisions. Thus, the extent to which private agents employ the class action mechanism to enforce the law is contingent upon their incentives to invest and the investment decisions they ultimately make throughout the multi-stage investment sequence. Against this backdrop, this Article examines the compound correlation between (i) the magnitude of private incentives to invest, (ii) the corresponding, aggregate level of investment, (iii) the magnitude of ex ante expected liability for systematic, mass-inflicted risk of harm and, consequently, (iv) the deterrence effects of class action law enforcement. Notwithstanding the observation that the specific properties of this correlation are highly law firmand context-specific, the analysis generates unambiguous insights into the general properties of this correlation. These insights are germane to making qualitative statements on the existence of discrete, privately-optimal level of investment in class action law enforcement; the existence of discrete social optima; and the efficacy of possible regulatory intervention to bridge the private-social incentive divergence.


Abstract Falls among older adults can lead to severe physical and psychological consequences. However, whether leisure participation changes after falling is not clear. We investigated whether falls resulted in reduced leisure participation in terms of duration, number, and intensity among older adults. Secondary data from the Health and Retirement Study and the Consumption and Activities Mail Survey (n = 1163) were analyzed. The results showed falls did not predict future leisure participation. Female, white, higher education, fewer functional limitations, and good balance were significant predictors of leisure participation at follow-up. Being white also predicted a significant decline in total number of leisure activities from baseline to follow-up, whereas higher education protected older adults from a significant reduction in total intensity of leisure activity. Our findings suggest falls may not directly affect leisure participation, but its risk factors, such as demographics, functional limitations, and balance, have a direct impact on leisure participation.


The introduction of intracytoplasmic sperm injection (ICSI) in 1992 has dramatically changed the management of severe male infertility. In severe male infertility, live birth rates with ICSI are superior to those with other non-donor treatments. In non-male infertility, however, pregnancy rates are not better with ICSI than with in vitro fertilization (IVF). With obstructive or non-obstructive azoospermia, reasonable pregnancy rates are now possible with ICSI after recovery of sperm from the testes followed by ICSI. Genetic counselling is indicated for severe male infertility, whether or not ICSI is considered. ICSI is indicated in preimplantation genetic diagnosis (PGD) to avoid contamination by extraneous DNA in the case of PCR-based testing and to increase the number of embryos available for testing. In turn, PGD may be indicated in pregnancies that are at high risk of aneuploidy because of genetic factors associated with azoospermia. As with IVF, not all couples succeed, but 2% of couples with failed ICSI cycles will conceive without treatment. ICSI outcome studies indicate that there is a significant increase in prematurity, low birthweight, and perinatal mortality associated with single and multiple births, similar to the outcomes of conventional IVF. However, as evidenced in long-term follow-up studies, the higher rates of urogenital abnormalities and increased use of healthcare may be associated with paternal characteristics.


We propose a two-layer control architecture for bilateral teleoperation with communication delays. The controller is structured with an (inner) performance layer and an (outer) passivity layer. In the performance layer, any traditional controller for bilateral teleoperation can be implemented. The passivity layer guarantees that, from the operator and environment perspective, the overall teleoperator is passive: The amount of energy that can be extracted from the teleoperator is bounded from below and the rate of increase of the stored energy in the teleoperator is bounded by (twice) the environment and operator supplied power. Passivity is ensured by modulating the performance layer outputs and by injecting a variable amount of damping via an energy-based logic that follows the innovative principle of energy duplication and takes into account the detrimental effects of time delays. In contrast to the traditional teleoperation approach, in which the master and slave controllers implement an as-stiff-as-possible coupling between the master and slave devices, our scheme is specifically designed for direct force-reflecting bilateral teleoperation: The slave controller mimics the operator action, whereas the master controller reflects the slave-environment interaction. We illustrate the performance of the two-layer approach in a challenging experiment with a round-trip communication delay of 300 ms while making and breaking contact with a stiff aluminum environment. Finally, we also compare our controller with the state of the art.


We have determined illite crystallinity, coal rank, percent 2M 1 white K-mica polytype, and phase assemblages for shales and shale-matrix melange from various areas in the Diablo Range. Additional information concerning metamorphic conditions and fluid composition was derived from stable isotope work and fluid inclusion measurements. This study presents new constraints on the pressure-temperature evolution of the Franciscan units from the Diablo Range. Several shales indicate a lower pressure, possibly higher temperature overprint on the peak pressure assemblages. Peak pressure assemblages include jadeitic pyroxene, sodic amphibole, lawsonite, aragonite, and phengite. Reactions, which indicate a lower pressure, possibly higher temperature overprint, are the transition from aragonite to calcite, the formation of albite from jadeitic pyroxene + quartz, the compositional gradient from phengite to muscovite in white K-mica, and the transition from sodic to calcic amphibole. The assemblage albite, calcic amphibole, lawsonite, and chlorite found in a single shale from Pacheco Pass indicates the transition from blueschist to greenschist facies conditions. We suggest that this transition occurred at a pressure and temperature of 5–8 kilobars and 300–350°C. Fluid inclusion data from post-kinematic quartz veins from the Mount Hamilton area support the idea of a lower pressure, possibly higher temperature metamorphic event. Pressure-temperature conditions of trapping early H 2 O- and CH 4 -rich fluids were 4.5 kilobars and ≈230°C. Geothermal gradients for the transition from blueschist to greenschist facies and the formation of early fluid inclusions are estimated to be ≈14°C/km. Illite crystallinity for all areas indicates diagenetic to high-grade anchizonal conditions; coal ranks are between 1.6% and 2.5% mean Ro. These estimates are not consistent with metamorphic conditions deduced for two different shale assemblages from Pacheco Pass, suggesting that illite crystallinity and coal rank are retarded. Poor illite crystallinity is thought to result from small coherent scattering domain sizes along c* of white K-mica crystals rich in a phengite component (Dalla Torre et al., 1994a, in press). The exact cause of the retardation of coal rank is not clear. The high pressure in the Diablo Range may have affected the maturation of organic matter. Our results imply that coal rank data from high-pressure terranes must be interpreted with caution if used as an absolute paleothermometer.


Pyrazole, previously reported to inhibit ethanol oxidation in the rat, also effectively blocks the in vivo metabolism of methanol, propanol, isopropanol, n-butanol, and isobutanol. A variety of oximes and amides are also effective inhibitors of ethanol metabolism. These various inhibitors may prove important in the elucidation of several facets of alcohol metabolism and also may have application in the treatment of methanol poisoning and in the reduction of the sequelae of the disulfiram-ethanol reaction syndrome in man.


Neuregulin (NRG), a growth and differentiation factor that signals via erbB receptor tyrosine kinases, has been shown to have biological effects in both the CNS and the peripheral nervous system. We report here that erbB4 is expressed in mature cerebellar granule cells, where it appears to be concentrated at the granule cell postsynaptic terminals. We also show that one form of NRG, Ig-NRG, plays a crucial role in aspects of cerebellar granule cell development in vitro. First, Ig-NRG treatment of granule cells in culture selectively induces the expression of the GABAA receptor β2 subunit. This increase in subunit expression is paralleled by an increase in functional GABAA receptors. In contrast to its effects on GABAA receptor subunit expression, Ig-NRG does not upregulate NMDA receptor N2B and N2C subunit expression. Second, we demonstrate that Ig-NRG also enhances neurite outgrowth from cultured granule cells. Ig-NRG does not, however, act as a survival factor for the granule cells. We have compared the effect of Ig-NRG with the effects of brain-derived neurotrophic factor (BDNF), a neurotrophin that exerts specific effects on granule cells in culture, and found that BDNF does not mimic the effects of Ig-NRG on GABAAreceptor subunit expression. Our results show that Ig-NRG has specific effects on granule cell development and maturation and may regulate these processes in vivo.


In this paper, we present a scheme towards the segmentation of English multi-oriented touching strings into individual characters. When two or more characters touch, they generate a big cavity region at the background portion. Using Convex Hull information, we use these background information to find some initial points to segment a touching string into possible primitive segments (a primitive segment consists of a single character or a part of a character). Next these primitive segments are merged to get optimum segmentation and dynamic programming is applied using total likelihood of characters as the objective function. SVM classifier is used to find the likelihood of a character. To consider multi-oriented touching strings the features used in the SVM are invariant to character orientation. Circular ring and convex hull ring based approach has been used along with angular information of the contour pixels of the character to make the feature rotation invariant. From the experiment, we obtained encouraging results.


Voluntary prepayment plans are making a worthwhile contribution to health security and have important potentialities. Beginning in 1932 hospital service plans have developed to the point where there are seventy-eight of such plans in the United States, with an enrolment of over 16,000,000 persons. Before the end of the year it is likely that plans will exist in all states. At the present time in three states over 30 per cent of the population of the state is enrolled and in seven states between 20 and 30 per cent of the population are enrolled., In a number of urban centers—Cleveland, Ohio, Rochester, N. Y., Rockford, Ill.—to name a few, over 50 per cent of the population belong to the hospital service plan. At the present time there are in operation nineteen medical service plans sponsored by local and state medical societies. These plans have a total enrolment of


STUDY QUESTION
Can cultured follicles model the ovarian cycle, including follicular- and luteal-phase hormone synthesis patterns and ovulation?

SUMMARY ANSWER
Under gonadotrophin stimulation, murine follicles grown in an encapsulated three-dimensional system ovulate in vitro and murine and human follicle hormone synthesis mimics follicular and luteal phases expected in vivo.

WHAT IS KNOWN ALREADY
Studies of the human ovary and follicle function are limited by the availability of human tissue and lack of in vitro models. We developed an encapsulated in vitro follicle growth (eIVFG) culture system, which preserves 3D follicular structure. Thus far, the alginate system has supported the culture of follicles from mice, dog, rhesus macaque, baboon and human. These studies have shown that cultured follicles synthesize steroid hormones similar to those observed during the follicular phase in vivo.

STUDY DESIGN, SIZE, DURATION
Cultured murine follicles were treated with human chorionic gonadotrophin (hCG) and epidermal growth factor (EGF) and either assayed for luteinization or removed from alginate beads and assayed for ovulation. Human follicles were also cultured, treated with follicle-stimulating hormone (FSH), hCG and EGF to mimic gonadotrophin changes throughout the ovarian cycle, and culture medium was assayed for hormone production.

PARTICIPANTS/MATERIALS, SETTING, METHODS
Murine and human follicles were cultured in alginate hydrogel and hormone production [17β-estradiol, progesterone, inhibin A, inhibin B, activin A and anti-Müllerian hormone (AMH)] was quantified in medium by enzyme-linked immuno assay (ELISA). Human ovarian tissue was acquired from females between 6 and 34 years of age with a cancer diagnosis. These participants were undergoing ovarian tissue cryopreservation at National Physicians Cooperative sites as part of the Oncofertility Consortium.

MAIN RESULTS AND THE ROLE OF CHANCE
When grown in this system, 96% of mouse follicles ovulated in response to hCG and released meiotically competent eggs. Ovulated follicles recapitulated transcriptional, morphologic and hormone synthesis patterns post-luteinizing hormone (LH/hCG). In addition to rodent follicles, individual human follicles secreted steroid and peptide hormones that mimicked the patterns of serum hormones observed during the menstrual cycle.

LIMITATIONS, REASONS FOR CAUTION
This was a descriptive study of an in vitro model of ovulation and the ovarian hormone cycle. The ovulation studies were limited to murine tissue and further studies are needed to optimize conditions using other species.

WIDER IMPLICATIONS OF THE FINDINGS
The eIVFG system reliably phenocopies the in vivo ovarian cycle and provides a new tool to study human follicle biology and the influence of cycling female hormones on other tissue systems in vitro.

STUDY FUNDING/COMPETING INTERESTS
This work was supported by NIH U54 HD041857, NIH U54 HD076188, NIH UH2 E5022920, NIH UH3 TR001207 and F30 AG040916 (R.M.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.


Ground water is a vital source for agricultural sector and rural communities. The global climate change is expected to change the hydrometeorological processes parameters. The climate considered as part of the southern Iraqi desert general climate with long, extremely hot, and dry summer and short wet period with little rain.  So it is vital to investigate the groundwater quality for irrigation purposes. The meteorological data of Samawa meteorological station for the period 1980-2015 was used to evaluate the climatic conditions for Muthana Governorate. It was found that the averages of annual rainfall was 105.7mm and the everages of evaporation is 3182 mm, while the mean monthly relative humidity % , mean temperature, wind speed  and sunshine were  40.9 %, 25.3 C o , 5.2m/sec and 9 h/day respectively. The results show that the mean evapotranspiration is 1717 mm, while the correct evapotranspiration is 1520 mm and the climate of the study area is classified as dry. And water deficit equals to (72%) of the total rainfall amount, and water surplus formed (28%) of the total rainfall amount.


BACKGROUND
A 10% prevalence of intracranial aneurysms in patients with coarctation of the aorta has been described in a few studies. Our objective is to describe the rate of intracranial aneurysm detection in patients with coarctation of the aorta in the current era. We hypothesise that, with earlier detection and coarctation of the aorta intervention, the rate of intracranial aneurysm is lower than previously reported and screening imaging may only be warranted in older patients or patients with certain risk factors.

METHODS
This is a retrospective study of 102 patients aged 13 years and older with coarctation who underwent brain computed tomography angiography, magnetic resonance imaging (MRI), or magnetic resonance angiography between January, 2000 and February, 2018.

RESULTS
The median age of coarctation repair was 4.4 months (2 days-47 years) and the initial repair was primarily surgical (90.2%). There were 11 former smokers, 4 current smokers, and 13 patients with ongoing hypertension. Imaging modalities included computed tomography angiography (13.7%), MRI (41.2%), and magnetic resonance angiography (46.1%), performed at a median age of 33.3 years, 22.4 years, and 25 years, respectively. There were 42 studies performed for screening, 48 studies performed for neurologic symptoms, and 12 studies performed for both screening and symptoms. There were no intracranial aneurysms detected in this study.

CONCLUSIONS
These results suggest that the rate of intracranial aneurysms may be lower than previously reported and larger studies should explore the risk of intracranial aneurysms in coarctation of the aorta in the current era.


In this paper, we present a unified architecture known as Transfer-Editing and Recognition Generative Adversarial Network (TER-GAN) which can be used: 1. to transfer facial expressions from one identity to another identity, known as Facial Expression Transfer (FET), 2. to transform the expression of a given image to a target expression, while preserving the identity of the image, known as Facial Expression Editing (FEE), and 3. to recognize the facial expression of a face image, known as Facial Expression Recognition (FER). In TER-GAN, we combine the capabilities of generative models to generate synthetic images, while learning important information about the input images during the reconstruction process. More specifically, two encoders are used in TER-GAN to encode identity and expression information from two input images, and a synthetic expression image is generated by the decoder part of TER-GAN. To improve the feature disentanglement and extraction process, we also introduce a novel expression consistency loss and an identity consistency loss which exploit extra expression and identity information from generated images. Experimental results show that the proposed method can be used for efficient facial expression transfer, facial expression editing and facial expression recognition. In order to evaluate the proposed technique and to compare our results with state-of-the-art methods, we have used the Oulu-CASIA dataset for our experiments.


This paper proposes an ecosystem services–based integrated water resource management (IWRM) framework within which a participatory Bayesian network (BN) model that 15 assists with the integration of IWRM is developed. The framework is divided three steps: (1) identifying water-related services of ecosystems; (2) analysis of the tradeoffs and synergy among users of water; and (3) ecosystem services–based IWRM implementation using the BN model. We present the development, evaluation and application of a participatory BN model with the involvement of four participant groups (stakeholders, water manager, water management experts, 20 and research team) in Qira oasis area, Northwest China. As a typical catchment-scale region, the Qira oasis area is facing severe water competition between the demands of human activities and natural ecosystems. We demonstrate that the BN model developed provides effective integration of ecosystem services into a quantitative IWMR framework via public negotiation and feedback. The network results, sensitivity evaluation, and management scenarios are broadly accepted by the 25 participant groups. The intervention scenarios from the model conclude that any water management measure remains unable to sustain the ecosystem health in water-related ecosystem services. Greater cooperation among the stakeholders is highly necessary for dealing with such water conflicts. In particular, a proportion of the agricultural water saved through improving water-use efficiency should be transferred to natural ecosystems via water trade. The BN model 30 developed is appropriate for areas throughout the world in which there is intense competition for water between human activities and ecosystems – particularly in arid regions.


Objective: To assess differential item functioning and observed mean differences across two modes of administration for PROMIS® measure scores in a sample of adults with traumatic injury. Method: Items from 7 PROMIS® adult measures (v1.0 Physical Function, Fatigue, Pain Interference, Anger, Anxiety, and Depression and v2.0 Social Health—Emotional Support) were administered as fixed-length short forms in random order to a cross-sectional sample. Participants were randomly assigned to interviewer-administered (phone or in-person) or self-administered (via the Assessment Center website) conditions. The research was conducted at 5 medical rehabilitation institutions across the U.S. Participants included 277 adults with spinal cord injury (n = 148) or traumatic brain injury (n = 129). Results: DIF analyses indicated that all items were invariant to mode of administration. There was no significant effect of mode of administration for the majority of PROMIS® measures tested. Regarding observed scores, there were small but significant effects of mode of administration on the Emotional Support and Depression measures, with participants in the interview condition reporting better support/fewer symptoms. Conclusions: PROMIS® instruments demonstrated measurement equivalence across interviewer-administered and self-administered conditions. These findings are particularly important for research or clinical applications where administration of PROMIS® measures by independent web- or tablet-based administration is not ideal, for example with individuals with physical or cognitive disabilities or with individuals who lack computer and/or Internet access. PROMIS® v1.0 Depression and PROMIS® v2.0 Emotional Support scores displayed a tendency toward social desirability that should be considered when these measures are interviewer-administered.


An increasing number of companies are using data analytics to improve their products, services, and business processes. However, learning knowledge effectively from massive data sets always involves nontrivial computational resources. Most businesses thus choose to migrate their hardware needs to a remote cluster computing service (e.g., AWS) or to an in-house cluster facility which is often run at its resource capacity. In such scenarios, where jobs compete for available resources utilizing resources effectively to achieve high-performance data analytics becomes desirable. Although cluster resource management is a fruitful research area having made many advances (e.g., YARN, Kubernetes), few projects have investigated how further optimizations can be made specifically for training multiple machine learning (ML) / deep learning (DL) models. In this work, we introduce FlowCon, a system which is able to monitor loss functions of ML/DL jobs at runtime, and thus to make decisions on resource configuration elastically. We present a detailed design and implementation of FlowCon, and conduct intensive experiments over various DL models. Our experimental results show that FlowCon can strongly improve DL job completion time and resource utilization efficiency, compared to existing approaches. Specifically, FlowCon can reduce the completion time by up to 42.06% for a specific job without sacrificing the overall makespan, in the presence of various DL job workloads.


Abstract Significant developments in the effective teaching of control education over the past few decades, since the emergence of new software and IT technologies, have made control education more efficient. Animated Tutorials are a clear illustration of this, and will aid control engineering students in their quest to study control topics in a productive and cost effective manner. This paper discusses how these animated tutorials can benefit control engineering students. However, there is a need for educators to work more closely with Multimedia and Software development in conjunction with animated tutorials to make teaching more effective.


Abstract This article uses the resource scarcity-violence model of Homer-Dixon (1999) to analyse the drivers of conflicts between ethnic groups that shared the pre-colonial ethnic frontiers of trans-Jubaland–Wajir and competed over water sources during the colonial period in the Northern Frontier District (NFD) of Kenya from 1903 to 1939. The article shows that pre-colonial ethnic conflicts were not induced by resource scarcity. Rather, extended periods of peace punctuated by conflicts were associated more with social and political relations. By contrast, the colonial period, with far more restrictive resource access to wells and the grazing lands, resulted in structural changes in resource scarcity. Colonial resource governance was incapable of stopping the pressures from migrants threatening resident populations. Residents were finally displaced and former alliances broken up. The competition resulted in violent conflicts due to structural changes that altered rights to resources.


Chronic biliary tract disease is the third most common indication for orthotopic liver transplantation (OLT) in the United States. Most patients undergoing OLT for chronic biliary tract disease have end-stage liver disease associated with cirrhosis, but a minority are transplanted in the precirrhotic stage for indications that can include poor quality of life (eg, intractable pruritis or fatigue), recurrent ascending cholangitis, or cholangiocarcinoma. A smaller subset of these patients suffer from severe noncirrhotic portal hypertension that can be associated with histologic features of nodular regenerative hyperplasia (NRH) and/or obliterative portal venopathy. We reviewed 306 liver explants performed for chronic biliary tract disease at 2 institutions during 1995 to 2003 to identify patients who were transplanted in the precirrhotic stage. The following clinical data were recorded: age, sex, type of biliary tract disease, radiology, clinical symptoms, signs of portal hypertension, pretransplant shunting procedures, time between diagnosis and OLT, and primary indication for OLT. Histopathologic data included: explant weight, gross appearance, fibrosis stage (1 to 4), cholangitis, bile duct dysplasia, malignancy, portal vein thrombi, presence of NRH, and presence of obliterative portal venopathy. Twenty-six of 306 (8.5%) patients underwent OLT in the precirrhotic stage (12 females: 14 males, mean age of 46 y, age range 12 to 68 y). At explant, fibrosis stage ranged from 1 to 2 (portal and periportal fibrosis) to 3 (multiple bridging fibrosis). Underlying biliary tract disease included primary sclerosing cholangitis (18 cases), primary biliary cirrhosis (5 cases), autoimmune cholangitis (2 cases), and secondary sclerosing cholangitis (1 case). Primary indications for OLT were recurrent cholangitis and/or decreased quality of life (11 cases), complications of portal hypertension (6 cases), portal hypertension plus cholangitis/decreased quality of life (5 cases), and malignancy (4 cases). Of the 11 patients with portal hypertension as a major indication for transplant, 2 had undergone transjugular intrahepatic portal-systemic shunting and 3 others had portal vein thrombi. Histopathologically, NRH was prominent in 8 of these 11 patients (73%) and obliterative portal venopathy in 6 (55%). NRH was also present in 4 of the 15 (27%) patients who were transplanted for other indications. These results indicate that precirrhotic portal hypertension is a predominant or major contributing factor to OLT in a significant minority (11 of 306, 3.3%) of patients with chronic biliary tract disease. The occurrence of NRH in some patients transplanted for other indications suggests it is a histologic pattern that can precede the development of clinically significant portal hypertension.


In December 2015, the government of Ontario introduced the Fertility Program, a plan to publicly fund in vitro fertilization (IVF). The Fertility Program seeks to use the advanced reproductive technology to reduce the occurrence of multiple births and to increase access to fertility treatments. This paper does not argue that IVF should not be publicly funded at all, but rather posits that in a time when the government is restricting healthcare spending, scarce resources must be allocated appropriately. The Ontario government has failed to craft a cost-effective funding program to maximize these limited resources by expanding the role of healthcare to a point that is unsustainable. While the Fertility Program makes steps towards achieving its goals, it fails to implement a comprehensive regulatory scheme and provide financial assistance to those with the greatest need. The province's failure to provide exclusion criteria to access funding allows the government to escape accountability by deferring public policy decisions to individual fertility clinics. In light of these shortcomings, several reforms to the Fertility Program are suggested and the implications of the Fertility Program going forward have been identified.


Despite its high and direct impact on nearly all biological processes, the underlying structure of gene-gene interaction networks is investigated so far according to pair connections. To address this, we explore the gene interaction networks of the yeast Saccharomyces cerevisiae beyond pairwise interaction using the structural balance theory (SBT). Specifically, we ask whether essential and nonessential gene interaction networks are structurally balanced. We study triadic interactions in the weighted signed undirected gene networks and observe that balanced and unbalanced triads are over and underrepresented in both networks, thus beautifully in line with the strong notion of balance. Moreover, we note that the energy distribution of triads is significantly different in both essential and nonessential networks compared with the shuffled networks. Yet, this difference is greater in the essential network regarding the frequency as well as the energy of triads. Additionally, results demonstrate that triads in the essential gene network are more interconnected through sharing common links, while in the nonessential network they tend to be isolated. Last but not least, we investigate the contribution of all-length signed walks and its impact on the degree of balance. Our findings reveal that interestingly when considering longer cycles the nonessential gene network is more balanced compared to the essential network.