Circadian rhythms play critical roles in regulating metabolism, including daily feeding/fasting periods and oscillating expressions of certain genes. Glucokinase (Gck) , expressed in the liver and pancreas, is central for whole-body glucose homeostasis by acting as a glucose sensor and regulating metabolism according to prevailing glucose levels. Gck expression has also been shown to follow a circadian rhythm. Gck activators (GKAs) effectively reduce hyperglycemia, however, adverse events have also involved hypoglycemia, hyperlipidemia, and hepatic steatosis. Given the circadian rhythmicity and natural postprandial activation of Gck, we hypothesized that GKA treatment would benefit from being timed specifically during feeding periods. We compared the metabolic effects following differentially timed administrations of the GKA AZD1656 in the obese, insulin resistant Zucker rat. Four weeks of continuous treatment significantly improved glycemic control; however, hepatic steatosis and inflammation manifested. In contrast, a robust reduction in hepatic steatosis and inflammation on top of improved glycemia, was observed when AZD1656 administration was timed to feeding periods only. When AZD1656 was timed to fasting periods, detrimental metabolic effects were observed, including impaired glycemic control, severe liver steatosis and elevated inflammation. Mechanistically, timing AZD1656 administration to feeding periods was found to divert de novo lipogenesis-derived lipids away from hepatic storage towards VLDL synthesis and secretion, without affecting plasma triglyceride levels. In conclusion, intermittent AZD1656 dosing timed to feeding periods promotes glucose disposal when needed the most, while the daily drug holiday allows for maintained metabolic flexibility and avoids hepatic steatosis. Chronotherapeutic approaches should be considered for the development of GKAs and other drugs acting on metabolic targets.

 T. Kroon: Employee; AstraZeneca. I. Alexandersson: Employee; AstraZeneca. A. Ferm: Employee; AstraZeneca. M. Petersson: Employee; AstraZeneca. S. Maurer: Employee; AstraZeneca, Merck Sharp & Dohme Corp. B. Zarrouki: Employee; AstraZeneca. K. Wallenius: Employee; AstraZeneca. N.D. Oakes: Employee; AstraZeneca. J. Boucher: Employee; AstraZeneca, Evotec International GmbH.


This paper asserts that the role of blogs cannot be adequately understood without examining the established media context in which they appear. Blogs operate along side, in conjunction with, and in opposition to established vehicles for political information, which creates tension among journalists seeking to preserve their authority. As a site to observe the blog-traditional journalism relationship, this article examines the reaction by journalists and others to blogs' role in US Election Day 2004 coverage. Much of the attention by journalists focuses on assessing the well-publicized decision by some blogs to release incomplete exit polls erroneously predicting a victory for Democratic candidate John Kerry. This discourse works to make sense of the status and credibility of blogs while simultaneously allowing journalists to negotiate their role as authoritative providers of political news. Ultimately, the discourse underlines the dynamism of news in a contemporary media environment marked by new forms of complexity and competitiveness.


To improve the security of the smart grid, quantum key distribution (QKD) is an excellent choice. The rapid fluctuations on the power aerial optical cable and electromagnetic disturbance in substations are two main challenges for implementation of QKD. Due to insensitivity to birefringence of the channel, the stable phase-coding Faraday—Michelson QKD system is very practical in the smart grid. However, the electromagnetic disturbance in substations on this practical QKD system should be considered. The disturbance might change the rotation angle of the Faraday mirror, and would introduce an additional quantum bit error rate (QBER). We derive the new fringe visibility of the system and the additional QBER from the electromagnetic disturbance. In the worst case, the average additional QBER only increases about 0.17% due to the disturbance, which is relatively small to normal QBER values. We also find the way to degrade the electromagnetic disturbance on the QKD system.


59155902 : Major DESIGN ARTS (INTERNATIONAL PROGRAM) Keyword : CERAMICS, RECYCLED GLASS, INTEGRATION AND DECORATIVE LIGHTING MRS. WEERAYA JUNTRADEE : CERAMICS AND RECYCLED-GLASS INTEGRATION METHODOLOGY STUDY:AN APPLICATION OF DECORATIVE LIGHTING DESIGN. THESIS ADVISOR : ASSISTANT PROFESSOR VEERAWAT SIRIVESMAS, Ph.D. Ceramics and glass exist in the same group of materials; compounded by the same inorganic substances and with which when treated with heat exhibit a very similar transformation process. However, they are structurally different resulting in varying rates of expansion and shrinkage. This creates incompatibility problems, in the form of excessive cracks or stresses when they are combined. This research aims to experiment to find possibilities of combining ceramics and recycled glass for decorative lighting design regarding both materials share similar characteristics with regard to passage of light and their translucency. The research methodology was related to practice based research, consisted of research in art and design and pure practice process which were implemented to identify potential compatibility and combining techniques. The development of these techniques were based-on a review of relevant literature, analyzed and concluded into 3 possible processing routes. Quartz added bone china clay body was identified and used with recycled bottle and window glass in the exploration. The kiln-formed techniques; fusing, slumping and casting were used to create the prototype artwork. Design inspiration was drawn from "Star ceiling: patterns and elements from Thai Traditional Architecture" and simplified version of these elements were used in the design to make contemporary artworks while at the same time maintaining a sense of Thainess and reflecting the artistic identity of the researcher. The experimentations results are present in the prototype artworks as follow; lighting sculptures, stained glass partition and table lamps which are demonstrated the translucency enhancement of ceramic clay body combining with recycled glass. Furthermore this research also expected to raise society's awareness and aesthetic appreciation of ceramic and recycled glass design which will be able to benefit the further development of creative art and eco-friendly design product in the future.


Self-regulated learning (SRL) is an active and constructive process whereby learners set goals for their learning, monitor, regulate, and control their cognition and motivation behaviours as well as the contextual features of the learning environment. Self-regulated learning (SRL) helps learners to choose what to learn, determine how long they want to learn, determine how to learn, access relevant instructional materials effectively, as well as assessing their level of comprehension of learning materials (Zimmerman, 1989). Several studies have revealed that self-regulated learning (SRL) variables such as goal setting, monitoring and help seeking have been shown to have significant impact on the learners' academic performance (Paris & Paris, 2001, Narciss et al. 2007). According to Pintrich & Zusho, (2002), if students regulate their learning effectively, they will definitely achieve their academic goals. Reaching these goals successfully during science learning will lead to greater understanding of the scientific concepts being taught; however, students are not always effective at regulating their learning (Paris & Paris, 2001). Research has shown that students may fail to use self-regulatory skills for many reasons; for example, students may not have prior knowledge or know when to apply certain regulatory strategies during learning processes in order to meet their set goals. Students may also not engage in planning their learning through goals setting as well as monitoring their progress toward the set goals within the learning context. Students may not even know when to seek help from a peer or teacher and finally they may not be motivated about their learning tasks (Azevedo et al., 2003, Narciss et al. 2007). The context of the learning situation within the classroom plays an important role in how students self-regulate their learning behaviours, when they use technology learning tools such as computer supported collaborative learning (CSCL) environment.


This paper was written in the course of the ALAQS project (Airport Local Air Quality Studies) held by EUROCONTROL since 2003. The ALAQS project aims at defining best practice for conducting airport emission inventories and dispersion studies. As a consequence, a test bed toolset was developed: ALAQS-AV. One of the advantages of ALAQS-AV is its high flexibility which allows conducting emission calculations with various methods within the tool. Furthermore, ALAQS-AV output is expected to provide reliable input for a wide range of dispersion models: Gaussian, Lagrangian and Eulerian. The objective of this study was to estimate the impact of an aircraft take-off weight on its take-off and climb-out emissions, which occur in the vicinity of airports and influence the airport local air quality. Obviously aircraft weight influences engine performances, which result in different climb profiles to reach an altitude of 3000 ft. The 3000 ft limit is a commonly accepted limit altitude for airport emission inventories. It is obvious that the greater the weight of an aircraft and the longer the time it takes to reach 3000 ft. However this is not considered in most actual air quality tools. take off weight for widely used aircraft types (Yak 40, Boeing 747-400 and 767-300, Tupolev Tu-134, Airbus A320, …). Quantities emitted of CO, HC, NOx, PM10 are calculated and compared as well as the geographical extent of the exhaust areas. The climb profiles used in this study originated from the INM tool (Integrated Noise Model, FAA) which is used world wide for noise estimations at airports. They were implemented in the ALAQS-AV tool, developed on behalf of EUROCONTROL, to estimate airport emissions. Results proved that the impact of take off weight on climb emissions is significant. In the worst case, emissions of NOx are almost doubled. The horizontal extent of the pollution goes from ~5 km to ~10 km for large jet aircraft. For the covering abstract see ITRD E135582


Introduction: Immune reconstitution inflammatory syndrome (IRIS) is defined by various clinical manifestations following the initiation of antiretroviral treatment (ART) in HIV patients primarily infected with Mycobacteria. IRIS has clinical similarities with lepromatous reactions in patients with leprosy following antibiotic initiation. Areas covered: Tuberculosis and more rarely lepromatous leprae and Whipple's disease are the main diseases caused by actinobacteria associated with IRIS, regardless of HIV status. The pathogenesis of this syndrome remains complex and partially understood. The treatment for IRIS is non-evidence-based, except for corticosteroids in tuberculosis-IRIS. Thalidomide and other immunomodulatory drugs have been successfully used in case series. Expert opinion: IRIS is mainly observed during infections (viral, fungal or bacterial) which involve inefficient macrophages for the clearance of bacteria, namely Actinobacteria such as Mycobacterium leprae, M. tuberculosis and Tropheryma whipplei. The restoration of macrophage competence after ART or antibiotic initiation results from a complex mechanism, probably involving a sudden and violent immune reaction with a cytokine storm, such as TNF-α and IFN-γ. This overreaction might be controlled using corticosteroids and thalidomide.


Hospital is a very important institution to provide health care for people. It is not surprising that nowadays the people's demands for hospital is increasing. However, due to the rising cost of healthcare services, hospitals need to consider efficiencies in order to overcome these two problems. This paper deals with an integrated strategy of staff capacity management and bed allocation planning to tackle these problems. Mathematically, the strategy can be modeled as an integer linear programming problem. We solve the model using a direct neighborhood search approach, based on the notion of superbasic variables.


This paper presents a methodology for predicting Myocardial Ischemic Beats from ECG signal using a Nonlinear Autoregressive Neural Network with Exogenous inputs (NARX) model. This technique utilizes the features extracted by integrating independent component analysis (ICA) and Wavelet packet decomposition (WPD) on ECG for detecting Myocardial Ischemic beats. At first, the denoised ECG beat segments are projected on the bases to create the independent component (IC) vectors. Further, these IC vectors are disintegrated by WPD. The feature set for distinguishing ischemic beats is extracted by calculating entropy, mean and standard deviation from wavelet coefficients. These features are input to NARX model for uncovering ischemic beats from normal beats. Several architectures of NARX models were tested for predicting myocardial ischemic beats. The efficacy of NARX architectures are assessed by comparing MSE and correlation coefficient. The NARX model with 2 hidden neurons and 2 delay lines provided the best results with a MSE of 0.0002 and correlation coefficient 0.99, which implies that the NARX neural network has huge potential in the prognosis of Myocardial Ischemic Beats.


The facile synthesis of 16-hydroxygeranylgeraniol(1), a naturally existing alicyclic diterpene, by alkylation reaction of allylic iodide(3) with phenyl sulfone(4), is described.


A geometric approach is introduced to study permutation polynomials over a finite field. As an application, we prove that there are no permutation polynomials of degree 2/ over a large finite field, where / is an odd prime. This proves that the Carlitz conjecture is true for n = 21. Previously, the conjecture was known to be true only for n < 16.


In contrast with media constructed as vast, ontologically homogeneous, non-localized systems, formats show material networks of interoperability and exclusions, inscribed in local specificities, and involving precise conditions for the circulation of images and sounds. Formats, institutionalized as standards, frame the "technical networks" defined by Gilbert Simondon, that unfold technical objects into economically and politically structured webs that cover the world. Media are always formatted and, as such, do not flow: they are displaced.


Cuckoo Search (CS) is a meta-heuristic optimization algorithm that is inspired by breeding strategy of some cuckoo species that involves laying of eggs in the nests of other host birds. Like other population based optimization algorithms, the initial positions of the population, in the case of CS are host nests, will influence the performance of the searching. Based on this fact, we believe that the CS algorithm can further be improved by strategically selecting the starting positions of the nests instead of the standard random selection. This work suggests the use of positions generated from the Centroidal Voronoi Tessellations (CVT) as the starting points for the nests. A CVT is a Voronoi tessellation of a set such that the generators of the Voronoi sets are simultaneously their centers of mass. The CVT will initially present the problem space in equally distributed manner. The performance of CS algorithm initialized using CVT is compared with those generated from the standard CS algorithm on several benchmark test functions. The results show that the initialization of CS algorithm using the CVT improves its performance especially for benchmark functions with high-dimensional input spaces.


To recognize the nature and distribution of various vegetation types, it is necessary to have an accurate area inventory, species composition list, and classification of plant communities. In a sub-tropical forest of the Western Ghats, we investigated the spatial variation of rainforest tree community structure and composition to establish if forest structure and diversity is varied as a function of altitude. In the present study, we describe the structure and composition of tropical forest in Silent Valley National Park (SVNP) with emphasis on the different altitudes and habitats. Three major habitats in the study area were selected based on elevation between 900 and 2300 msl. The major habitats were grasslands and evergreen forests at an altitude below 1400 m. Between 1400 and 1800 m, broadleaved hill forests were dominant. Above 1800 m, Shola forest was observed and above 2000 m Shola forest interspersed with the grasslands were prominent. All trees greater than 30 cm diameter were marked and measured in sixty 20 x 20 m plots in the forest across the elevational gradient of 900 to 2300 msl. We identified and tagged 1872 individuals with 152 species of trees belonging to 109 genera in 41 families. Forest structure and composition varied significantly across altitudinal gradient. We elucidate patterns of forest structure and diversity in the context of the disturbance, topography, logging and altitude. We conclude with the argument that conservation of forest across the altitudinal gradient is essential to maintain the forest structure to ensure the uninterrupted gene flow.


Pillage games (Jordan, 2006a) have two features that make them richer than cooperative games in either characteristic or partition function form: they allow power externalities between coalitions; they allow resources to contribute to coalitions' power as well as to their utility. Extending von Neumann and Morgenstern's analysis of three agent games in characteristic function form to anonymous pillage games, we characterise the core for any number of agents; for three agents, all anonymous pillage games with an empty core represent the same dominance relation. When a stable set exists, and the game also satisfies a continuity and a responsiveness axiom, it is unique and contains no more than 15 elements, a tight bound. By contrast, stable sets in three agent games in characteristic or partition function form may not be unique, and may contain continua. Finally, we provide an algorithm for computing the stable set, and can easily decide non-existence. Thus, in addition to offering attractive modelling possibilities, pillage games seem well behaved and analytically tractable, overcoming a difficulty that has long impeded use of cooperative game theory's flexibility. © 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).


Maternal cardiorespiratory compromise has been reported to occur during the treatment of preterm labor with tocolytic agents. The risk for these complications is increased by the following factors: multiple gestation, the combination of magnesium sulfate and β‐adrenergic agonist, and the use of adrenocortico‐steroids to hasten fetal pulmonary maturity. A case is presented of labor at 28 weeks' gestation complicated by pulmonary edema associated with the three risk factors listed above. The β‐agonist was discontinued with resolution of pulmonary edema. Intravenous magnesium sulfate was continued for 11 days. When uterine contractions finally overcame the tocolysis, delivery occurred. It appeared that uterine quiescence was achieved through the continued use of magnesium sulfate despite pulmonary edema in this case. The risk of continued tocolysis seemed to be counterbalanced by the benefits of prolonged intra‐uterine existence for the fetuses.


We appreciate suggestions presented by Gharebaghi and Heidary regarding our article titled "The Shiraz Pediatric Eye Study – a PopulationBased survey of School – Age Children: Rationale, Design, and Baseline Characteristics".[1] In that study, we aimed to provide a valid source of data via a standard protocol and effective quality assurance strategies. Our article had just described the design, methods, eye examination techniques, and baseline characteristics of the participants. Although the two mentioned studies[2, 3] were conducted on a small fraction of the same population, we did not find any scientific justifications to cite them in this publication. They might be cited in future articles from the Shiraz Pediatric Eye Study, if it was deemed necessary. Their suggestions regarding the prevalence of visual impairments, associations of the race and age with the ocular structures, and the continuing cohort of biometric data are useful. Considering the specific goals of our study (last paragraph of introduction),[1] we have planned to apply the mentioned suggestions and much more in future publications of the Shiraz Pediatric Eye Study.


Background: In the past decades, a number of non-invasive methods have emerged for detecting and estimating liver fibrosis; these include both serum-based panels and imaging-based technology. Some of these methods are now being incorporated in clinical practice. However, the limitations of the current techniques include lack of organ specificity, sampling errors and limited ability to reflect the efficacy of interventions. Key Messages: Novel magnetic resonance (MR)-based techniques provide an opportunity to bring about further changes in the investigations and management of patients with liver diseases. Multimodal quantitative MR techniques enable the estimation of fat, iron accumulation, degree of liver injury/inflammation and fibrosis within the whole liver without the need for administering contrast agents. Architectural changes within the liver can be evaluated concurrently with portal haemodynamic changes allowing non-invasive assessment of portal hypertension and effects of interventions. A combination ultra-high field (7T) provides greater sensitivity with a potential to distinguish inflammation from fibrosis on imaging and determine specific types of fats (saturated vs. unsaturated) present within the liver using MR spectroscopy. 13C MR spectroscopy can estimate glutathione flux and rate of beta oxidation in-vivo providing novel tools for experimental studies that evaluate the efficacy of interventions as well as underlying mechanisms. Conclusions: Translational research should focus on converting the potentials of these innovative methodologies into clinical applications for the benefit of patients.


Background: Toxoplasma gondii is an obligatory intracellular parasite that is consider a major invasive parasite in immunocompromised individuals. Objective: To determined the prevalence of Toxoplasmosis in patients with different types of cancer in Iraq. Patients and Methods: Samples of blood were gathered from 258 women who included 112 healthy controls samples and 146 samples with different types of cancer. They were attended Oncology Teaching Hospital in the Medical City Hospital in Baghdad province from October, 2016 to February, 2017. Then the sera were tested to determine the anti- T. gondii antibodies (IgG and IgM) using enzyme linked immunosorbent assay. Results : The highest seropositive rate of T. gondii IgG were noted in patients with lymph node cancer followed by breast, colorectal, liver, pancreas, lung, ovary, prostate cancer which was (100%, 77.50%, 77.42%, 75.00%, 66.67%, 66.67%, 54.55%, 28.57%) respectively with significant differences (P<0.01). This study focused on breast and colorectal cancer. According to the age groups, the seroprevalence of anti- T. gondii IgG was the highest in the age group (26-35) years in patients with colorectal and breast cancer which was (378.309 IU/ml, 374.561 IU/ml respectively) compared with control group (148.917 IU/ml). In regard to the anti- tumor dosage, the highest mean titer of IgG observed in dosage (0), the mean titer of IgG in patients with colorectal and breast cancer whose were seropositive to anti-T. gondii IgG were (242.016 IU/ml and 227.275 IU/ml) respectively, while in seronegative patients to anti-T. gondii IgG were (8.594 IU/ml and 6.011 IU/ml) respectively. Conclusion : These finding suggest that incidental rate of toxoplasmosis is higher in cancer patients. Thus, the incidental rate of toxoplasmosis could be considered as an indication to the high risk of cancer. In addition, anti- T. gondii IgG test has to be taken into consideration as markers for staging cancer disease.


Introduction: A key feature of home care is its divided nature. Conditions for coordination are poor. A variety of professionals provides a coherent mix of services. The social care system is in general local, less professionalised and usually more poorly financed than the health care system. These differences are related to or result in different interests, culture and style and are a ground for communication problems. The existence of this divide will be explored it will be considered what remedies are available and are applied. Methods and Materials: This presentation is drawn upon the results of the EC-financed EURHOMAP project and a discussion between country experts invited to the conference. The study has collected a wealth of data on various types of home care (including nursing care, personal care, domestic aid and respite care). In 31 countries information was gathered on a large set of indicators in the areas of policy & regulation, financing, organisation & delivery and clients & informal carers. Results: Home care services may stem from different sectors, systems and organisations. Several countries have identified and addressed problems related to this situation. However, the degree of splitting varies among countries. It can exist at one or more of the following levels: governance and regulation; entry to the home care system; delivery of services. Furthermore the extent to which the division occurs may differ as well. Integration at governance level creates more favourable conditions for integration at access and delivery level. From a clients' perspective poor integration may manifest itself both at the point of entry (absence of a clear-cut easy access point), and in the delivery of services (which are not tailored to what is needed or lack flexibility). Conclusion: There are many possible remedies against problems of poor integration; depending on the level and the situation where the problem occurs.(aut. ref.)


This paper investigates whether or not the share prices of soccer clubs listed on the London Stock Exchange and the Alternative Investment Market are influenced by the soccer teams' weekly sporty performances. Event studies corrected for thin trading and with Baysian updating reveal that at the first day of trading after a game, positive abnormal returns almost 1% were realised expected following a soccer victory. In contrast, defeats or draws are penalised, respectively, by negative abnormal returns of 1.4% and 0.6%. Cumulatively over the week, defeats and draws trigger abnormal losses of 2.5% and 1.7%. These findings are consistent across the English and Scottish, national Cup and European competitions. Much larger abnormal returns are generated subsequent to promotion and relegation games as the Premier League and European games guarantee substantially higher (future) income in terms of television broadcasting rights and sponsoring income. Whereas victories seem to be more rewarded by share price increases for those clubs listed on the LSE in comparison to those listed on the AIM, defeats lead to larger price reductions for AIM listed clubs. In spite of the sporty performance sensitivity of listed soccer clubs and the excellent share price performance of certain clubs like Manchester United, Sunderland and Celtic, Jensen's alpha and the Sharpe ratio of an equally weighted investment in listed soccer clubs since 1996 points out that such an investment has substantially underperformed the market index.


Abatmct- A model describing relations and interactions between local vessel resistances and tissue temperatures during extra-corporeal circulation (ECC) is described and developed from first principles. Unknown model parameters are estimated by means of an extended Kalman Filter from real patient data. Estimated model parameters produced good model performance in tracking patient data and produced meaningful physiological results. This approach is a necessary first step in modeling further physiological interactions in the body during hypothermic ECC.


Recent years have witnessed the rapid growth of smart devices and mobile applications. However, mobile applications are typically computation-intensive and delay-sensitive, while User Devices (UDs) are usually resource-limited. Mobile Edge Computing (MEC) has been proposed as a promising paradigm to mitigate the tension, where UDs' tasks could be executed either locally on itself or remotely on the edge server via computation offloading. Lots of efficient computation offloading scheduling approaches have been proposed, whereas most of them are based on centralized scheduling which could face troubles in large-scale MEC. To address the issue, this paper proposes a distributed scheduling framework by leveraging the idea of 'centralized training and distributed scheduling'. Furthermore, the Actor-Critic reinforcement learning is adopted to build the framework where the Actor and Critic play the roles of distributed scheduling and centralized training, respectively. Extensive simulations are conducted and the experimental results verify the effectiveness and efficiency of the proposed framework.


Author(s): Axelrad, Lee | Abstract: State governments in the U.S. have increasingly been promoting their business climate and products abroad. The motivation behind these efforts at "global promotion" might seem obvious to persons acquainted with export base theory. According to this theory, growth in a region's total economy-usually measured in either jobs or income -is a function of growth in its export or "basic" sectors; one builds an economy by building exports.Export base theory has been a mainstay of economic development literature, and students of economic development theory probably would not be surprised to see state governments across the country engaging in global promotion. Thus, policy-makers in this area appear to be applying a well-established theory to the practical problem of enhancing economic development.


A fifth order operational transconductance amplifier-C (OTA-C) Butterworth type low-pass filter with highly linear range and less passband attenuation is presented for wearable bio-telemetry monitoring applications in a UWB wireless body area network. The source degeneration structure applied in typical small transconductance circuit is improved to provide a highly linear range for the OTA-C filter. Moreover, to reduce the passband attenuation of the filter, a cascode structure is employed as the output stage of the OTA. The OTA-based circuit is operated in weak inversion due to strict power limitation in the biomedical chip. The filter is fabricated in a SMIC 0.18-μm CMOS process. The measured results for the filter have shown a passband gain of −6.2 dB, while the −3-dB frequency is around 276 Hz. For the 0.8 VPP sinusoidal input at 100 Hz, a total harmonic distortion (THD) of −56.8 dB is obtained. An electrocardiogram signal with noise interference is fed into this chip to validate the function of the designed filter.


Creative intelligence is relevant to all aspects of the school curriculum, yet it is through art and design that pupils may come to experience the significance of creativity as a means of exploring innovative and original ideas which offer credence to the individual and affect approaches to learning. This article analyses creativity and the creative process and addresses the links between creativity and intelligence by examining the implications such factors may hold for the teacher when developing approaches to learning in art and design. It focuses in particular on the use of sketchbooks within the context of a number of Art and Design GCSE courses and explores how students have been provided with opportunities to develop creative responses to set tasks. In addition, it sets out to challenge the notion that the requirements of GCSE assessment criteria inevitably restrict creativity and lead to non-creative formulaic practice.


Brain decoding, a paradigm that consists of predicting stimuli or mental states from concurrent functional brain data, is steadily gaining popularity in neuroimaging based research. While the machine learning and pattern recognition techniques involved in classification-based analysis are getting more and more sophisticated, the statistical methods used for the evaluation of the obtained results are not developing at the same speed. This represents a problem because inadequately evaluated results can be misleading and further claims based on them might be unfunded. This PhD thesis presents a sound procedure for the evaluation of classification results from brain decoding experiments overcoming some limitations of current common practice. An evaluation method within the Bayesian hypothesis testing framework, namely Bayesian test of independence, is presented, which recasts the question whether there is evidence that the classifier has learned from data to discriminate the classes or not as a test of independence between predicted and true class labels. Within the multi-class setting a classifier can learn the complete discrimination of all classes or only subsets of classes. The Bayesian test for partial independence is derived for the latter case. This approach closes a gap as common practice methods do not allow for analysis of potential subsets except for additional binary analysis.
Data from simulated and real experiments are considered when comparing the novel methods to common practice. The proposed procedure is robust with imbalanced datasets, it reduces potential issues that arise when having a single null-hypothesis, there is the possibility to incorporate prior knowledge for the learning case, it is compatible with small sample size test sets, and it prevents the misleading interpretation of the estimated prediction accuracy. Experimental evidence shows, that the proposed Bayesian test of independence not only addresses the question whether learning from data has taken place or not but also that it can be successfully used in settings where common practice tests are stressed to their limits.


Traditional approaches to brand-building dictate that success in branding can only result from communicating a single differentiating claim (or promise) with exceptional clarity and unwavering consistency. Hence, brands have been built on the back of single-minded propositions that remained fixed and unchanging through successive cycles of advertising and promotions. This whitepaper argues that the above model of brand positioning is an artifact of an old mass media order in which scarcity was the overriding norm. Media fragmentation and digital media are now offering brand practitioners an expansive choice of touch points, and in the process altering the very fundamentals of marketing and strategic brand management. This paper presents the case for building brands by communicating every credible brand proposition - not just one chosen 'hit' - in relevant and profitable contexts, to different consumer segments. It also outlines 8 concrete ways for marketers and advertising agencies to harness the power of the long tail in brand communication - reaping complex, layered and engaging brands without sacrificing clarity or simplicity in advertising.


A prerequisite for any animal's survival is the ability to make decision about its sensory world. Here we show that (1) Drosophila can make discrete and firm choices among behavioural alternatives on the basis of small difference in the saliency of visual cues( color/shape and color/position dilemma); (2) Mushroom bodies in Drosophila brain are likely site for such choice behavior; (3) Dopamine neurons in Drosophila play a key role in the coding of negative reward (or punishment) probability and uncertainty behavior. Information received by the nervous system through multiple sensory modalities must be processed in an integrated manner. Different modalities of sensation interact in a synergistic or antagonistic manner during sensory perception, but whether there is also interaction during memory acquisition is largely unknown. in Drosophila reinforcement learning, we found that conditioning with concurrent visual and olfactory cues facilitated memory acquisition near the threshold level that was ineffective for unimodal conditioning and that this bimodal conditioning reduced the threshold for unimodal memory retrieval. Furthermore, bimodal preconditioning followed by unimodal conditioning with either visual or olfactory cue led to crossmodel memory transfer. Thus crossmodal memory acquisition exists in Drosophila and interactions between sensory modalities may play an important role for learning in a natural environment.


Finite-dimensional Lie algebras over an algebraically closed field of positive characteristic representable as a sum (not necessarily direct) of two nilpotent subalgebras are studied. Necessary and sufficient conditions are obtained for a Lie algebra to be decomposable into a sum of two Cartan subalgebras.Bibliography: 4 titles.


The Getty Museum inaugurates a new series of affordable publications that introduce the public to the richness of its holdings in illuminated manuscripts. The first in the series features Italian manuscript illumination from the ninth to the sixteenth centuries. This volume showcases full-colour reproductions of masterpieces by Niccolo da Bologna, Pisanello, Girolamo da Cremona, Taddeo Crivelli, Giovanni di Paolo, Matteo da Milano, Antonio da Monza, and the Master of Gerona, among a number of Italy's finest illuminators. The selection includes multiple illuminations from such sumptuous volumes as the Montecassino Breviary, the Gualenghi-d'Este Hours, the Missal of the Anti-Pope John XXIII, and the recently discovered Orsini Missal, along with exceptional leaves from the celebrated choir books of Santa Maria degli Angeli, Florence, and from the laudario of the Compagnia di Sant'Agnese, Florence. J. PAUL GETTY MUSEUM


Aim: This study aimed: to develop and validate an LC-MS/MS method for mycophenolic acid, tacrolimus, sirolimus, everolimus and cyclosporin A in oral fluid (OF), as an essential tool to study the usefulness of OF as an alternative matrix for immunossuppressants' therapeutic drug monitoring; and to find the best OF collector for these analytes. Materials & Methods: Chromatographic separation was achieved using an XBridge® Shield RP18 analytical column maintained at 65ºC, using 2 mM ammonium formate and 0.1% formic acid in water (A) and acetonitrile (B) as mobile phase. OF sample was extracted with solid phase extraction after sonication and protein precipitation. Results & Conclusions: Method validation met all the acceptance criteria. LODs were 0.05-1 ng/ml, and LOQs 0.1-5 ng/ml. Silanized tubes offered the best recoveries. The method was successfully applied to 31 OF specimens, describing everolimus detection in OF for the first time. Conclusion: The proposed method is sensitive enough for the detection of OF trough concentrations in patients receiving immunosuppressants when using an appropriate OF collector.


Abstract. Anthropogenic carbon dioxide (CO2) emissions and their observed growing trends raise awareness in scientific, political and public sectors of the society as the major driver of climate-change. For an increased understanding of the CO2 emission sources, patterns and trends, a link between the emission inventories and observed CO2 concentrations is best established via Earth system modelling and data assimilation. In this study anthropogenic CO2 emission inventories are processed into gridded maps to provide an estimate of prior CO2 emissions for 7 main emissions groups: 1) power generation super-emitters and 2) energy production average-emitters, 3) manufacturing, 4) settlements, 5) aviation, 6) transport and 7) others, with estimation of their uncertainty and covariance to be included in the European Centre for Medium-Range Weather Forecasts (ECMWF) Integrated Forecasting System (IFS). The emission inventories are sourced from the Intergovernmental Panel on Climate Change (IPCC) 2006 Guidelines for National Greenhouse Gas Inventories and revised information from its 2019 Refinements, and the global grid-maps of Emissions Database for Global Atmospheric Research (EDGAR) inventory. The anthropogenic CO2 emissions for 2012 and 2015, (EDGAR versions 4.3.2 and 4.3.2_FT2015 respectively) are considered, updated with improved apportionment of the energy sector, energy usage for manufacturing and diffusive CO2 emissions from coal mines. These emissions aggregated into 7 ECMWF groups with their emission uncertainties are calculated per country considering its statistical infrastructure development level and sector considering the most typical fuel type and use the IPCC recommended error propagation method assuming fully uncorrelated emissions to generate covariance matrices of parsimonious dimension (7×7). While the uncertainty of most groups remains relatively small, the largest contribution to the total uncertainty is determined by the group with usually the smallest budget, consisting of oil refineries and transformation industry, fuel exploitation, coal production, agricultural soils and solvents and products use emissions. Several sensitivity studies are performed: for country type (with well-/less well-developed statistical infrastructure), for fuel type specification, and for national emission source distribution (highlights the importance of 30 accurate point source mapping). Uncertainties are compared with United Nations Framework Convention on Climate Change (UNFCCC) and the Netherlands Organisation for Applied Scientific Research (TNO) data. Upgraded anthropogenic CO2 emission maps with their yearly and monthly uncertainties are combined into the CHE_EDGAR-ECMWF_2015 dataset (Choulga et al., 2020) available from https://doi.org/10.5281/zenodo.3712339 .


Acoustics issues such as noise in the workplace remains one of the most prevalence occupational hazard especially in the manufacturing industry with heavy machineries. Increasing mechanization in all industries and most trades has since proliferated the noise problem. In Malaysia, much has been studied and is known about the auditory effects of noise. However less attention has been given to the non-auditory effects of noise such as annoyance, stress, and work performance, and concern about such effects is a relatively recent phenomenon. In view of this, this study aims to determine the level of noise from different type of machines and tools in a manufacturing plant and also the effects of noise to the employees. A structured questionnaire was used to assess the effects of noise on the workers and sound level meter was used to measure the noise level at selected work areas. The results of this study showed that nearly all the identified work areas exceeded the action level of 85 dB(A) and four of these areas noise levels' are more than 90 dB(A) which is the permissible exposure limit according to the Factories and Machinery (Noise Exposure) Regulations 1989. For the questionnaire, it was found that annoyance topped the noise effects list with 51.4%, followed by stress with 40.0%, hearing deterioration (14.3%) and job performance deterioration (2.9%). As a conclusion, noise control or preventive measures are suggested in order to minimize the health risks from noise exposure.


Vitis amurensis Ruprecht contains a large number of polyphenolic compounds which are biologically active components. For the most efficient and safe extraction supercritical carbon dioxide was used. In this work, for the first time, a comparative metabolomic study of biologically active substances of wild grapes collected from five different places of the Primorsky and Khabarovsk territories is carried out. To identify target analytes in ethanol extracts of grape berries, high performance liquid chromatography (HPLC) was used in combination with an amaZon SL ion trap (manufactured by BRUKER DALTONIKS, Germany) equipped with an ESI electrospray ionization source in negative and positive ion modes. The mass spectrometer was used in the scan range m / z 100 - 1.700 for MS and MS / MS. Used fragmentation of the 4th order. Primary mass spectrometric results showed the presence of 89 biologically active compounds corresponding to the species V. amurensis, moreover, salvianolic acids F, D and G, oleanoic, ursolic, myristoleic acids, berbericinin, mearnsetin, esculin, nevadensin, stigmasterol, fucosterol, phlorizin, L-tryptophan identified for the first time in V. amurensis.


Abnormalities of glucose metabolism and hyperinsulinemia have been demonstrated in patients with end-stage renal disease and may contribute to the development of atherosclerotic complications in these patients. In the present study, we investigated the stage of renal failure in which abnormalities of glucose metabolism develop and whether these abnormalities were associated with an increased prevalence of cardiovascular events in patients with early renal failure. In 321 untreated essential hypertensive patients, we assessed renal function by measuring 24-h creatinine clearance, urinary protein excretion, and microalbuminuria; we assessed cardiovascular status by clinical and laboratory tests; and we measured plasma glucose, insulin, and C-peptide levels at fasting and after a 75-g oral glucose load. To evaluate insulin sensitivity, a hyperinsulinemic-euglycemic clamp was performed in a subgroup of 104 patients. Patients with creatinine clearance < 30 ml.min(-1).1.73 m(-2), severe hypertension, BMI < 30 kg/m(2), and diabetes or family history of diabetes were excluded. Hypertensive patients were found to be hyperinsulinemic when compared with 92 matched normotensive subjects. Early renal failure (creatinine clearance < 90 ml.min(-1).1.73 m(-2)) caused by hypertensive nephrosclerosis was detected in 116 of 321 patients. Analysis of patients with varying degrees of renal function impairment demonstrated increased plasma glucose and insulin response to oral glucose load, decreased fasting glucose-to-insulin ratio, and reduced sensitivity to insulin only in those patients with creatinine clearance < 50 ml.min(-1).1.73 m(-2). Parameters of glucose metabolism were not correlated with creatinine clearance and microalbuminuria. Prevalence of atherosclerotic cardiovascular events was significantly related to reduction of creatinine clearance, but parameters of glucose metabolism were comparable in patients with and without evidence of atherosclerotic damage. Thus, in patients with hypertensive nephrosclerosis and early impairment of glomerular filtration, alterations of glucose metabolism become evident only when creatinine clearance is < 50 ml.min(-1).1.73 m(-2) and are not related to microalbuminuria and cardiovascular complications.


We consider the unsupervised learning problem of assigning labels to unlabeled data. A naive approach is to use clustering methods, but this works well only when data is properly clustered and each cluster corresponds to an underlying class. In this paper, we first show that this unsupervised labeling problem in balanced binary cases can be solved if two unlabeled datasets having different class balances are available. More specifically, estimation of the sign of the difference between probability densities of two unlabeled datasets gives the solution. We then introduce a new method to directly estimate the sign of the density difference without density estimation. Finally, we demonstrate the usefulness of the proposed method against several clustering methods on various toy problems and real-world datasets.


ABSTRACT: Light is one of the factors that influence the germination and initial establishment of orchids under in vitro cultivation. This study evaluated the effect of different light sources on these stages in in vitro cultivation of Schomburgkia crispa Lindl. After sowing in an aseptic environment, we stored the cultures in a screened greenhouse (natural light) or in a growth room with the following light sources: 3,000 K yellow LED; 6,500 K white LED [1]; 6,500 K white LED [2]; or 6,500 K white fluorescent lamp (control). We assessed germination percentage and initial seedling establishment at 45 and 90 days after sowing. Light did not influence the germination of S. crispa. However, the use of 3,000 K LED provided a faster initial establishment of S. crispa when compared to the other light sources, also presenting lower seedling mortality. Thus, the light source 3,000 K LED is a potential substitute for the 6,500 K fluorescent lamps and LEDs used in growth rooms in in vitro culture laboratories.


Objective: Against the background of increasing risk for hypertension in adolescents, we decided to investigate blood donation as an opportunity to compare national guidelines for identification of individuals, between 16–19 years of age, meeting hypertension criteria. Design and method: 16–19 year old volunteers donating blood between 2015 and 2020 were enrolled. They were asked to identify their ethnicity. Those declining were identified as "other''. Blood pressure was measured using automated equipment (Welch Allyn, ProBP). We compared the European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines for hypertension (> = 140/90 mmHg) with the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for hypertension (> = 130/80 mmHg). Results: There were 71912 participants, 63.2% (45441) and 36.8% (26471) were female and male respectively. Conclusions: More males, by comparison with females, met hypertension guideline criteria in all ethnicities. The prevalence of hypertension was highest in African Americans. Depending on which international hypertension criteria are chosen, there are significant differences in the size of population of 16–19 year olds identified for attention. Determining a suitable threshold that will justify investigation their investigation and treatment will require long term clinical trials.


An immunoadsorbent specific for the carboxy-terminal sequence -GAPER, which comprises residues 502-506 of the alpha-polypeptide of ovine sodium and potassium ion activated adenosinetriphosphatase [(Na+ + K+)-ATPase], was used to isolate the products of the reaction between the lysine immediately preceding this sequence in the intact protein and either [3H]acetic anhydride or fluorescein 5'-isothiocyanate. Changes in the apparent nucleophilicity of this lysine, Lys501, were observed with both reagents when ATP was bound by the intact, native enzyme poised in the E1 conformation or when the structure of the enzyme was changed from the E1 conformation into the E2-P conformation. With both reagents, a decrease of more than 4-fold in the yield of incorporation occurred during the former change, but a decrease of only 2-fold occurred during the latter. Because a much larger decrease occurred when ATP was bound in the absence of a conformational change than occurred when a major conformational change took place in the absence of the occupation of the active site, these changes in the incorporation of [3H]acetyl suggest that Lys501 from the alpha polypeptide is directly involved in binding ATP within the active site of (Na+ + K+)-ATPase. The immunochemical reactions between the specific polyclonal antibodies raised against the sequence-GAPER and denatured or enzymically active (Na+ + K+)-ATPase were also investigated. Western blots and the inhibition of enzymic activity caused by the antibody have shown that it can bind to both the denatured and the native form of the alpha-polypeptide, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Hereditary hemolytic anemias (HHAs) embrace a highly heterogeneous group of chronic disorders with a highly variable clinical picture. HHA encompass (1) hyporegenerative anemias (HAs), as congenital dyserythropoietic anemias (CDAs); (2) hemolytic anemias due to red cell membrane defects (HAMDs), as hereditary spherocytosis (HS) and hereditary stomatocytosis (HST). Although the workflow to diagnose these conditions is a normal clinical practice, differential diagnosis, classification, and patient stratification among HHAs are often very difficult. Beyond achieving a definitive diagnosis, knowing the genetic basis of these patients can be valuable also for guiding treatment. Next generation sequencing (NGS) refers to non-Sanger-based high-throughput DNA sequencing technologies. This technology plays a major role either in disease gene discovery or in clinical use for establishing a genetic diagnosis. Particularly, the major current application of NGS in diagnostics is through design of disease specific panel, named targeted (t)-NGS, in which a selected fraction of genes is sequenced.
The primary aim of our study was the development of a fast, accurate, reliable and cost effective diagnostic/prognostic tool for HHAs based on t-NGS. In order to assess the reliability of this approach we created a t-NGS gene panel, named RedPlex, composed by 34 loci causative or candidates of HHAs. In silico design was performed by Agilent SureDesign web tool. For each locus, all coding regions, 5' and 3'UTRs, and 100 bp flanking splice junctions were included. Sequence length was set at 150×2 nucleotides, and the predicted target size amounted to 538 regions (239.764 kb). Targeted enrichment was performed on 32 patients from 27 unrelated families by HaloPlex Target Enrichment System. High-throughput sequencing was performed by Illumina NextSeq 500. SureCall software was used for bioinformatic and computational analyses. RedPlex panel showed high sensitivity and specificity. It was able to capture at least 99.4% of 538 target regions with high and uniform coverage. We were able to obtain a conclusive diagnosis in approximately 72% of cases. In addition, a lot of patients (39%) showed multiple disease-associated variants suggesting complex inheritance. Indeed, t-NGS approach also allows the identification of "polygenic" genotypes, which may account for the phenotypic variability among HHA patients. Thus, the secondary aim of this project was the study of the interaction between mutated genes in HHA patients. We particularly focused on the functional interaction between two CDA-related genes, GATA1 and SEC23B. The demonstration of the direct interaction of GATA1 transcription factor on the SEC23B promoter provided also an explanation of the variability of phenotypes GATA1-related by means of the crosstalk of this gene with its target SEC23B.


Melatonin (N-acetyl-5-methoxytryptamine) is a pleiotropic signaling molecule that plays a crucial role in the regulation of various environmental stresses, including heat stress (HS). In this study, a 100 μM melatonin (MT) pretreatment followed by exposure to heat stress for different time periods was found to efficiently reduce oxidative stress by preventing the over-accumulation of hydrogen peroxide (H2O2), lowering the lipid peroxidation content (malondialdehyde (MDA) content), and increasing proline (Pro) biosynthesis. Moreover, the activities of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), were increased substantially in MT-pretreated wheat seedlings. The presence of MT significantly improved the heat tolerance of wheat seedlings by modulating their antioxidant defense system, activating the ascorbate–glutathione (AsA–GSH) cycle comprising ascorbate peroxidase (APX), and increasing glutathione reductase (GR) activities. It also held the photosynthetic machinery stable by increasing the chlorophyll content. Enhancement in the endogenous MT contents was also observed in the MT+HS-treated plants. Furthermore, the expression of reactive oxygen species (ROS)-related genes TaSOD, TaPOD, and TaCAT, and anti-stress responsive genes, such as TaMYB80, TaWRKY26, and TaWRKY39, was also induced in MT-treated seedlings. Due to these notable changes, an improvement in stress resistance was observed in MT-treated seedlings compared with control. Taken together, our findings suggest that MT can play a key role in boosting the stress tolerance of plants by modulating the antioxidant defense system and regulating the transcription of stress-responsive genes.


Globally, one of the public health problems confronting the medical community is maternal mortality. This study seeks to investigate the relationship between maternal mortality, proteinuria and pregnancy induced hypertension among some pregnant mothers in Ghana. In this study, protein in the urine and blood pressure of some 450 pregnant women who visited the Hospital between Januarys to December, 2015were monitored. Retrospective data based on maternal death from January 2010 and December 2015 were also retrieved and analysed. This was augmented by interviewing150 respondents (75 each from antenatal and postnatal section of the hospital) based on maternal health history, knowledge on PIH etc. The results of the study with respect to proteinuria and the blood pressure (BP) monitoring showed that, 36% of these mothers had traces of protein in their urine whiles 32 mothers out of 450 had elevated systolic and diastolic BP. The study also revealed, when data on maternal mortality and PIH of pregnant mothers were retrieved that, a total of 75, 439 (N=75,439) mothers attended the antennal section of the Hospital. Out of this, 139 of them (0.18%) died due to PIH. Maternal child bearing behaviour, nulliparity when analysed showed that, greater proportions of antenal (AN) mothers (32.00%) were nulliparous compared to their PN counterpart (0%) (p<0.0001). Results of our study has shown that, maternal mortality due to PIH were high due to elevated systolic and diastolic blood pressure as well as high doses of trace amount of protein in pregnant mothers' urine.


Supervised and semi-supervised source separation algorithms based on non-negative matrix factorization have been shown to be quite effective. However, they require isolated training examples of one or more sources, which is often difficult to obtain. This limits the practical applicability of these algorithms. We examine the problem of efficiently utilizing general training data in the absence of specific training examples. Specifically, we propose a method to learn a universal speech model from a general corpus of speech and show how to use this model to separate speech from other sound sources. This model is used in lieu of a speech model trained on speaker-dependent training examples, and thus circumvents the aforementioned problem. Our experimental results show that our method achieves nearly the same performance as when speaker-dependent training examples are used. Furthermore, we show that our method improves performance when training data of the non-speech source is available.


Cysteine Dioxygenase is an enzyme that catalyses the reaction of cysteine to cysteinesulfinic acid and is thought to regulate the intracellular concentrations of its substrate. The enzyme may also be involved in the oxidation of exposed sulfidrils of protein and by implication, involved in cell signalling or regulation. Substrate and products of cysteine dioxygenase are known to be disrupted in a number of neurodegenerative diseases making the protein an important target for medical research. To date, the structure of the protein has not been solved. An understanding of its structure and reaction mechanism will further the understanding of the aetiology of a number of different pathologies. Its structure may also further the development of novel pharmacological drugs.


Specific features of the relief structure of the hard palate mucosa in relation to sex and age were studied in putrefactive corpses. The findings may be useful in forensic medical expert evaluations.


This research investigates executive functioning challenges faced by students in college. This research responds to a gap in the literature within college student development theories about the development of college students with learning differences, specifically executive function (EF) challenges. Five students with EF challenges were involved in a series of interviews throughout and concluding their first semester at a four-year, public institution. The transcripts were coded and analyzed to identify themes to describe their development through college student development vectors using Chickering and Reisser's (1993) theory as well as their perceptions of college for students with EF challenges.


We surveyed the actinosporean stages of fish myxosporeans at fish farms in Jiangsu Province, China, from 2011 to 2014. During the surveys, we identified 7 actinosporean types from 4 collective groups: echinactinomyxon (1 type), triactinomyxon (1 type), aurantiactinomyxon (1 type), and neoactinomyxum (4 types), released by the oligochaete Branchiura sowerbyi. The morphological characteristics and DNA sequences of these types are described here. Based on 18S rDNA sequence analysis, the actinosporean of echinactinomyxon type CZ with 4 branches at the end of the caudal processes was identified as Myxobolus wulii, and the neoactinomyxum type JD was identified as Thelohanellus wangi Yuan, Xi, Wang, Xie, Zhang, 2015 (JX458816), a recently nominated species from the gills of allogynogenetic gibel carp Carassius auratus gibelio. In addition, actinosporeans of aurantiactinomyxon type JD, neoactinomyxum type CZ-1, neoactinomyxum type CZ-2, and neoactinomyxum type CZ-3 showed high genetic similarity to T. wuhanensis (96.3-96.5%), T. nikolskii (98.0-99.1%), T. wuhanensis (97.8-98.9%), and T. hovorkai (98.7-98.9%), respectively. Phylogenetic analyses showed that these actinosporeans were robustly clustered in the Thelohanellus spp. clade.


Contrary to predictions of its demise, C remains a dominant programming language, especially in embedded systems. Speed and transparency dictate that it will be so for the next decade, despite its supposed unsuitability for programming parallel architectures. A flexible compiler development system is a unique vehicle to bend the C language and its implementation to the developers' will. Using hard-won experience in applying extended versions of C to diverse parallel architectures, C's potential in the dark ages of multi-core programming is examined.


The great Vis.n. u temple at Angkor Wat in north-central Kampuchea (Cambodia) is known to have been built according to an astronomical plan. In this note we show that the little-understood solar formula of the temple is identical to the one in the Śatapatha Brāhman. a. We propose that the Angkor Wat formula was an expression of the Śatapatha astronomy.


Today's farmer has a choice of nine major types of sprinkler systems and many
versions of each type. The nine major types are handmove, tow line, giant
sprinkler, side roll, side move with and without trail lines, solid set,
center-pivot, self-propelled straight lateral, and self-propelled gun traveler.
All sprinkler types except the handmove are mechanical-move systems. The first
six major types are stationary systems -- the sprinkler or sprinklers apply
water while operating in a fixed position in the field. The last three types
are moving systems -- the sprinkler or sprinklers apply water while continuously
moving over the field.

Uniform water distribution by sprinkler systems is essential to optimize crop
yield and quality; allow minimum sprinkler system capacity; conserve pumping
power, and make more efficient use of the available irrigation water supplies.
It is very important where the system is used to apply fertilizers and pesticides
in irrigation water. To obtain uniform water distribution in the soil
with sprinkler systems, the application rate should be equal to or less than
the intake rate and surface storage capacity of the soil so that there is no
runoff or water movement on the soil surface.


Introduction: urogenital mycoplasmas (Mycoplasma hominis, Ureaplasma urealyticum), despite being part of the normal flora of the vagina, are among the bacterial species most frequently involved in infertility of the couple. Objectives: to determine the incidence of urogenital mycoplasma in endocervix smear tests of patients in the Provincial Consultation Service for Infertile Couples, to classify the severity of the infection detected, and to identify sensitivity-resistance to different antimicrobials of the isolated genital mycoplasmas. Methods: across-sectional, observational, descriptive study of female infertility by genital mycoplasmas was conducted in Dr. Julio Rafael Alfonso Medina Provincial Gynaecobstetric Teaching Hospital of Matanzas, between the months of November 2014 and January 2015. The sample consisted of the 117 patients who met the inclusion criteria. Results: 56.4% of the samples tested were positive; the most common species was Ureaplasma urealyticum. Mild infections predominated in 59.09%. The most reported symptom was vaginal discharge (42.73%). Ureaplasmaurealyticum showed greater resistance to ofloxacin (82%). No resistance was found of Mycoplasma hominis against the antimicrobial drugs used in the investigation. Coinfections were more resistant to azithromycin (100%), ofloxacin (90%) and erythromycin (80%). Conclusions: the most common organism was Ureaplasma urealyticum. Mild infections predominated. Ureaplasma urealyticum showed to be more resistant than Mycoplasma hominis. Both were highly sensitive to pefloxacin and minocycline.


This paper uses the Fran system for functional reactive animation to give a simulation of a lift – or elevator – with many floors. The paper first introduces a two-floor version, and then indicates in detail how this is extended to give a simulation with an arbitrary number of floors and featuring more realistic animated graphics. The paper introduces those aspects of Fran relevant to the simulation, making it a self-contained tutorial on parts of Fran and how it is applied in practice. The full code for the system is available on the World Wide Web.


This paper presents an overview of some of the theory and application of stochastic minimal graphs in the context of entropy estimation for imaging applications. Stochastic graphs which span a set of extracted image features can be constructed to yield consistent estimators of Jensen's entropy difference for between pairs of images. Unlike traditional plug-in entropy estimates based on density estimation, stochastic graph methods provide direct estimates of these quantities. We review the stochastic graph approach to entropy estimation, compare convergence rates to that of plug-in estimators, and discuss a geo-registration application.


The purpose of this study was to test the hypothesis that H(2)O(2) decreases the amount of force produced by a given intracellular Ca(2+) concentration (i.e., the Ca(2+) sensitivity) in airway smooth muscle (ASM) in part by mechanisms independent of changes in regulatory myosin light chain (rMLC) phosphorylation. A new preparation was developed and validated in which canine ASM strips were first exposed to H(2)O(2) and then permeabilized with 10% Triton X-100 to assess the persistent effects of H(2)O(2) on Ca(2+) sensitivity. Experiments in which H(2)O(2) was administered before permeabilization revealed a novel mechanism that contributed to reduced Ca(2+) sensitivity independently of changes in rMLC phosphorylation, in addition to an rMLC phosphorylation-dependent mechanism. The mechanism depended on factors not available in the permeabilized ASM strip or in the buffer to which the strip was exposed, since there was no effect when H(2)O(2) was added to permeabilized strips. H(2)O(2) treatment of a maximally thiophosphorylated purified myosin subfragment (heavy meromyosin) significantly reduced actomyosin ATPase activity, suggesting one mechanism by which the phosphorylation-independent reduction in Ca(2+) sensitivity may occur.


The deoxyribonucleic acid (DNA) synthetic response of cultured lymphocytes to grass pollen antigens was significantly higher in 66 untreated atopic patients than in 15 non-atopic subjects (p less than 0.05). There was no correlation between the DNA synthetic response and the specific IgE antibody level as measured by radioallergosorbent test in the 81 subjects (r= 0.13; p greater than 0.2). The effect of immunotherapy on proliferative lymphocyte response and specific IgE antibody response to grass pollen antigens was evaluated prospectively in 22 atopic patients. The DNA synthetic response to grass pollen antigens was significantly reduced after immunotherapy (p less than 0.01) but the specific IgE antibody level did not change significantly.


To reduce time-to-market, more and more embedded system developers and system-on-chip designers rely on microprocessor-based design methodology. ARM processor has been a major player in this industry over the last 10 years. However, there are many restrictions on developing embedded software using ARM processor in the early design stage. For those who are not familiar with embedded software development environment or who cannot afford to have an expensive embedded hardware equipment, testing their software on a real ARM hardware platform is a challenging job. To overcome such a problem, we have designed VMA (Virtual ARM Machine), which offers easier testing and debugging environment to ARM based embedded system developers. Major benefits that can be achieved by utilizing a virtual ARM platform are (1) reducing development cost, (2) lowering the entrance barrier for embedded system novices, and (3) making it easier to test and debug embedded software designs. Unlike many other purely software-oriented ARM simulators which are independent of real hardware platforms, VMA is specifically targeted on SYS-Lab 5000 ARM hardware platform, (designed by Libertron, Inc.), which means that VMA imitates behaviors of embedded software as if the software is running on the target embedded hardware as closely as possible. This paper will describe how VMA is designed and how VMA can be used to reduce design time and cost.


We describe the effects of different tracheostomy techniques on intracranial pressure (ICP), cerebral perfusion pressure (CPP), and cerebral extraction of oxygen. We attempted to identify the main mechanisms affecting intracranial pressure during tracheostomy. To do so we conducted a prospective, block-randomized, clinical study which took place in a neurosurgical intensive care unit in a teaching hospital. The patients studied consisted of thirty comatose patients admitted to the intensive care unit because of head injury, subarachnoid hemorrhage, or brain tumor. Ten patients per group were submitted to standard surgical tracheostomy, percutaneous dilatational tracheostomy or translaryngeal tracheostomy. In every technique a significant increase of ICP (P < .05) was observed at the time of cannula placement. Intracranial hypertension (ICP > 20 mm Hg) was more frequent in the percutaneous dilatational tracheostomy group (P < .05). Cerebral perfusion pressure dropped below 60 mm Hg in eleven cases, more frequently during surgical tracheostomy. Arterial tension of CO2 significantly increased in all three groups during cannula placement. No other major complications were recorded during the procedures. At follow-up no severe anatomic or functional damage was detected. We conclude that the three tracheostomy techniques, performed in selected patients where the risk of intracranial hypertension was reduced to the minimum, were reasonably tolerated but caused an intracranial pressure rise and cerebral perfusion pressure reduction in some cases.


Abstract Aims: Compare the need for neonatal resuscitation procedures between newborn infants with and without meningomyelocele (MMC). Results: This retrospective case-control study included 94 neonates with MMC, defined as open spinal dysraphism with exposure of nervous tissue, and 94 controls without malformations, paired with MMC infants by gender, mode of delivery, gestational age and time of birth. Infants were born at a university hospital in São Paulo, Brazil, from 2001 to 2010. After adjusting for perinatal variables (prenatal care, maternal hypertension, birth during the day shift, cephalic presentation, meconium in the amniotic fluid, gestational age <37 weeks and small-for-gestational-age infants), MMC increased the chance of positive pressure ventilation at birth [odds ratio (OR) 4.55 95% confidence interval (CI) 1.82–11.41], intubation at birth (OR 3.94 95% CI 1.14–13.59) and 1-min Apgar score 95% CI 0.99–7.57). Conclusion: MMC is an independent factor associated with the need for positive pressure ventilation and intubation at birth.


An integrated reservoir characterization workflow, for structural uncertainty assessment and continuous updating of the structural reservoir model, by assimilation of production data, is presented. An ensemble of reservoir models, expressing explicitly the uncertainty resulting from seismic interpretation and time-to-depth conversion, is created. The top and bottom reservoir-horizon uncertainties are considered as a parameter for assisted history matching and are updated by sequential assimilation of production data using the Ensemble Kalman Filter (EnKF). To avoid modifications in the grid architecture and thus ensure a fixed dimension of the state vector, an elastic grid approach is proposed. The geometry of a base-case simulation grid is deformed to match the reservoir top and bottom horizon realizations. The method is applied to a synthetic example. The result is an ensemble of history-matched structural models with reduced and quantified uncertainty. The updated ensemble of structures provides a more reliable characterization of the reservoir architecture and a better estimate of the field oil in place.


CaHPO4 and SrHPO4 were investigated using Raman, 1H NMR and 31P NMR techniques to study the environment of their PO3−4 tetrahedra and the percentage of mobile protons. 1H NMR spectra at room temperature suggest the presence of three types of protons, in agreement with RX investigation. The percentage of mobile protons in SrHPO4 is greater than in CaHPO4 because Sr2+ is bigger than Ca2+. 31P NMR spectra at room temperature show two lines in the spectrum of SrHPO4, revealing an equal environment of two sets of pairs of PO3− 4 . The 31P NMR spectrum of CaHPO4, however, exhibits three lines. This result was confirmed using a cross polarization (CP) sequence program. The first peak is attributed to the first set of pairs of P(1)O4 units and the two other ones to P(2)O4 and P(2)O4 units.


Social media platforms have become an inevitable part of our daily lives. Companies that noticed the intense use of social media platforms started to use them as a marketing tool. Even ordinary people have become famous by social media and companies have been sending their products to them to try and advertise. Many people have gained a considerable amount of money in this way and today new jobs are emerged like "Youtuber" and "Instagram Influencer". Therefore, ordinary people realized the power of social media and many people started to strength their digital identity over social media. The question raising in people's mind is that "What is the difference between the influencers and the ordinary people who have also digital identity over social media?". This study examined Instagram influencers for five categories namely fashion, makeup, photography, travel, and fitness in Turkey. As an exploratory study, the relationship between the influencers' average number of posts, the number of likes, the number of views, the number of comments, number of followers, and the number of following were examined. As well as the engagement rates of the followers to the influencers were calculated. In addition, the words they mostly used in the captions of the posts were examined.


A geriatric health maintenance program, started in 1976 as a community medicine elective, has developed into an innovative model in humanistic health care. Junior and senior medical students act as live-in facilitators of comprehensive health care for the elderly tenants in publicly subsidized housing units. Students rotate emergency night and weekend calls and hold weekly health clinics at the housing units. Weekly seminars are given by faculty members during which case presentations by students and topics related to the complex problems of the elderly are discussed. Important aspects of this elective are experiential learning in humanistic health care, exposure to ambulatory well or stable elderly people, development of communication/interpersonal skills, and acceptance of responsibility. The program has been received enthusiastically by tenants, community physicians, students, and an increasing number of faculty members at the University of Oregon Health Sciences Center School of Medicine.


Attachment to the bad object has remained a durable, undertheorized clinical problem. With an extended clinical example, the experience of limit, in both patient and analyst, is examined as part of a dense undercurrent in the relationship, including transference, that gives rise to shifts in understanding the attachment to an unsatisfying internal object. Importantly, the patient's and the analyst's experiences of limit are "in play" during the process of changes in the patient's attachment to the bad object. The relation of patient and analyst to the patient's internal objects, including bad and unsatisfying objects, is where play itself begins. Limit itself is constitutive of play. The analyst's attempt to analyze his own thoughts and experience regarding limits in maintaining an empathic connection to the patient's psychic reality influences the patient's capacity to take in a new part of his or her experience.


The occurrence of intestinal metaplasia with colonic‐type sulphomucins: (abbreviated: s‐IM or s‐positive IM) in the gastric mucosa was studied in 125 patients with gastric carcinoma (GCA), 62 patients with pernicious anemia (PA), 301 and 183 first‐degree relatives of GCA and PA patients, 406 outpatients and in 358 controls matched from a large population sample. The sulphomucins (s‐mucins) were demonstrated histochemically in endoscopic biopsy specimens by using high iron diamine and Alcian blue (pH 1) methods. The prevalence of s‐IM, especially the strongly s‐positive IM, was significantly higher in GCA patients than in other series or controls of the same age group. Further, s‐IM was significantly more common in PA patients and its prevalence higher in GCA relatives and outpatients than in other series or controls. The occurrence of s‐IM was also age‐dependent and dependent on the extent of IM. It was suggested that the occurrence of s‐IM can be used as a sign of lesions that are more closely associated with GCA than IM is in general.


The aim of this study was to investigate the effects of Bioglue as a mechanical barrier with or without biphasic calcium phosphate (BCP) in a rat tibia model. Sixty Sprague Dawley male rats weighing 250 ± 20 g and 10 to 12 weeks of age were studied. Unicortical defects were created on the right tibia of all rats. Subjects were randomly divided into 3 groups. BioGlue group (24 rats); BioGlue alone, Graft group (24 rats); BioGlue + BCP and Control group; unfilled and uncovered (12 rats). Animals were euthanized at 7th, 21st, and 45th days postoperatively for histological and histomorphometric analyses. BioGlue material exhibited no adverse effects until the end of observation period. Bone-healing scores did not differ statistically between Control and BioGlue group, but found to be lower in Graft group on 21st and 45th days, (P < 0.001 and P < 0.01 on the 21st day and P < 0.01 and P < 0.05 on the 45th day, respectively). New bone formation in Graft group was found to be statistically different from Control group on the 7th and 21st days (P < 0.01 and P < 0.05 respectively), whereas no statistical difference was observed between BioGlue and Control group at all times. The present analysis indicates that BioGlue functioned well as a mechanical barrier allowing new bone formation. No additional benefit of combination treatment was detected in this study design and BCP did not offer any advantage for bone regeneration, thus it can serve as only a space maintainer.


In a scintillation detector, scintillation crystals are typically made into a 2-dimensional modular array. The location of incident gamma-ray needs be calibrated due to spatial response nonlinearity. Generally, position histograms-the characteristic flood response of scintillation detectors-are used for position calibration. In this paper, a position calibration method based on a crystal position lookup table which maps the inaccurate location calculated by Anger logic to the exact hitting crystal position has been proposed. Firstly, the position histogram is preprocessed, such as noise reduction and image enhancement. Then the processed position histogram is segmented into disconnected regions, and crystal marking points are labeled by finding the centroids of regions. Finally, crystal boundaries are determined and the crystal position lookup table is generated. The scheme is evaluated by the whole-body positron emission tomography (PET) scanner and breast dedicated single photon emission computed tomography scanner developed by the Institute of High Energy Physics, Chinese Academy of Sciences. The results demonstrate that the algorithm is accurate, efficient, robust and applicable to any configurations of scintillation detector.


Background The increased prevalence of coronary heart disease (CHD) in UK resident Indo-Asians is unexplained by the traditional cardiovascular risk factors of dyslipidaemia, hypertension, smoking and diabetes mellitus. C-reactive protein (CRP) has been implicated in the pathogenesis of CHD but the data on ethnic variation in CRP is conflicting. We therefore investigated whether CRP could help explain the increased prevalence of CHD in Indo-Asians. Design and methods We measured CRP, using a highly sensitive assay, in 102 men (63 Caucasians and 39 Indo-Asians) and 89 women (58 Caucasians and 31 Indo-Asians). All subjects, aged between 40 and 70 years, were nondiabetic and nonsmokers. Results Serum CRP correlated (P < 0.05) positively with coronary risk. Serum HDL cholesterol concentrations were lower (P<0.05) in Indo-Asian women when compared with Caucasian women, but otherwise the ethnic groups were matched for calculated coronary risk and cardiovascular risk factors. Serum CRP concentrations were similar in Indo-Asians (women 2.29 (1.52) mg/l {mean (SD)}; men 1.77 (1.46) mg/l) and Caucasians (women 2.23 (1.54) mg/l; men 1.94 (1.45) mg/l). Conclusions Altered CRP concentrations does not appear to be implicated in the increased prevalence of CHD in UK resident Indo-Asians.


It is desirable to construct a transmission matrix with full code rate as well as full transmit diversity in the design of space time block coding (STBC). For an arbitrary complex constellation, only full rate and full diversity signal matrix with size 2 by 2 is possible, said as Alamouti Code. For a real signal matrix with a size above 8 by 8, it is also impossible to acquire full code rate and full transmit diversity simultaneously. An efficient selective receiver switching scheme is proposed for STBC with the full code rate and non-orthogonal design. In the proposed scheme with the aid of beamforming, the authors divide the received signals into two groups according to the encoded matrix. By this way, the authors can eliminate the interference from the neighbouring signals almost by half. The simulation results with the example of matrix demonstrate that the proposed scheme can provide the improved performance and more under imperfect channel estimation.


SUMMARY The body axis plays a central role in tetrapod locomotion. It contributes to the work of locomotion, provides the foundation for the production of mechanical work by the limbs, is central to the control of body posture, and integrates limb and trunk actions. The epaxial muscles of mammals have been suggested to mobilize and globally stabilize the trunk, but the timing and the degree to which they serve a particular function likely depend on the gait and the vertebral level. To increase our understanding of their function, we recorded the activity of the m. multifidus lumborum and the m. longissimus thoracis et lumborum at three cranio-caudal levels in dogs while they walked, trotted and galloped. The level of muscle recruitment was significantly higher during trotting than during walking, but was similar during trotting and galloping. During walking, epaxial muscle activity is appropriate to produce lateral bending and resist long-axis torsion of the trunk and forces produced by extrinsic limb muscles. During trotting, they also stabilize the trunk in the sagittal plane against the inertia of the center of mass. Muscle recruitment during galloping is consistent with the production of sagittal extension. The sequential activation along the trunk during walking and galloping is in accord with the previously observed traveling waves of lateral and sagittal bending, respectively, while synchronized activity during trotting is consistent with a standing wave of trunk bending. Thus, the cranio-caudal recruitment patterns observed in dogs resemble plesiomorphic motor patterns of tetrapods. In contrast to other tetrapods, mammals display bilateral activity during symmetrical gaits that provides increased sagittal stability and is related to the evolution of a parasagittal limb posture and greater sagittal mobility.


This paper presents numerical simulations to study the heating of a two-dimensional (2D) solid target under an ion cluster interaction. 2D quantum hydrodynamic (QHD) model is employed for the heating of solid target to warm dense matter on a picosecond time scale. A Gaussian cluster is used to uniformly heat the solid target to a temperature of several eV. The density and temperature of the target are calculated by a full self-consistent treatment of the QHD formalisms and the Poisson's equation. The technique described in this paper provides a method for creating uniformly heated strongly coupled plasma states.


Academics have frequently used and endorsed the Public Participation Geographic Information System (PPGIS) approach for national park management. However, it is only minimally used by public agencies such as national park organisations. This study explores the potential that managers of Finnish national parks see in the PPGIS approach in the context of planning for the visitor use of parks. Ten semi-structured interviews with managers of Parks and Wildlife Finland were conducted. The managers perceived that PPGIS could help in optimising site management, and preferred PPGIS studies that are practical and clearly connected to planning site management actions. They envisioned a mobile phone application that would allow mapping visitor experiences on the spot. Overall, the managers were open to adopting place-based planning practices. The study increases the understanding of public agencies' views towards PPGIS. It also produces practical information for conducting PPGIS case studies as well as for integrating PPGIS tools into planning processes.


Abstract In this study, the effect of gradient and multi-layered porous media is assessed for the optimized properties and arrangement in the tested novel baffle design arrangement, which results in further enhancement in its thermo-hydraulic performance. The computational study is carried out using ANSYS FLUENT; wherein the permeability and porosity for each layer is varied. It's executed in two steps: case 1 – porous layers with variations implemented (constant, linear/stepwise, increasing/decreasing) and case 2 – porosity varied over the length. The findings show that the linear/stepwise increments in both cases give almost similar performance evaluation criteria (PEC) values. The increase in heat transfer rate and pressure drop can be compared using PEC, for better evaluation of the performance of different arrangements. With the simulation data genetic algorithm optimization model is used to find the optimal arrangement of the porous layers for both cases to maximize PEC further. The optimal arrangement for case 1 and case 2 taken individually, gives PEC of 2.425 and 2.401 respectively. And their simultaneous optimization gives highest PEC of 2.508. Additionally, to improve the heat transfer rate further, Al2O3 (5 w/v %) nanoparticles in water is tested with optimized conditions, which improves the PEC by almost double magnitude.


For most plant species growing in polluted areas genotoxicity assays are not available. We have studied the possibility of using the alkaline protocol of the Comet assay as a method for detecting induced DNA damage in a grass Calamagrostis epigejos, growing wild in highly polluted areas. To calibrate the Comet assay for C. epigejos, two model mutagens were applied: the monofunctional alkylating agent ethyl methanesulfonate (EMS) and gamma-rays. With increasing concentrations of EMS (0 to 10 mM, 18 h treatment at 26 degrees C) applied on excised leaves, the DNA damage, as expressed by the tail moment (TM) values, increased from 4.7 +/- 0.9 to 60.8 +/- 2.7 microns. After gamma irradiation (0 to 30 Gy) the TM value increased from 4.2 +/- 0.2 to 48.1 +/- 1.7 microns. A 24 to 72 h recovery of leaves after EMS treatment in an EMS-free medium did not result in a significant change in the induced EMS damage. By contrast, a 24 h recovery after gamma-irradiation led to a complete repair of DNA damage measurable by the Comet assay. We have measured the DNA damage in nuclei of leaves of C. epigejos plants growing in the area of a sediment reservoir with substrates from uranium mining, where the ore was exploited through leaching with sulfuric acid. The average specific activity of natural radionuclides measured in the substrate was for 226Ra = 11,818 Bq kg-1, for 232Th = 66 Bq kg-1 and for 40K = 75 Bq kg-1. No significant increase in the DNA damage in plants growing on the sediment substrate above the DNA damage in control plants was detected by the Comet assay.


Abstract Among his instrumental music, Victor Herbert's Second Cello Concerto, op. 30 (1894) in particular deserves greater attention, not only because it has become standard repertoire but because of its historical importance as a stimulus to Antonín Dvořák. An analysis of the piece reveals a subtly crafted composition that brilliantly exploits the resources of the cello—Herbert's own instrument—and that builds upon the composer's earlier work for cello and orchestra. The work also exhibits that stylistic amalgam of Irish, German, and American elements that characterize Herbert's operetta scores. Scholars have long appreciated the fact that the piece helped inspire Dvořák to attempt a cello concerto of his own (1895). But Herbert, as has been suggested in the case of George W. Chadwick, might have influenced Dvořák's "American" music more generally. In turn, Dvořák's music—in particular, his "New World" Symphony—seems to have left its mark on Herbert's Second Concerto. In short, Herbert and Dvořák—colleagues at New York's National Conservatory in the early 1890s—engaged in a sort of musical dialogue, one that reflected differing ideas concerning nationalism and American music.


In light of the favorable outcomes of few small, non-randomized clinical studies, the Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) to Hydroxychloroquine (HCQ) for hospitalized coronavirus disease 2019 (COVID-19) patients. In fact, subsequent clinical studies with COVID-19 and HCQ have reported limited efficacy and poor clinical benefits. Unfortunately, a robust clinical trial for its effectiveness is not feasible at this emergency. Additionally, HCQ was suspected of causing cardiovascular adverse reactions (CV-AEs), but it has never been directly investigated. The objective of this pharmacovigilance analysis was to determine and characterize HCQ-associated cardiovascular adverse events (CV-AEs). We performed a disproportionality analysis of HCQ-associated CV-AEs using the FDA adverse event reporting system (FAERS) database. The FAERS database, comprising more than 11,901,836 datasets and 10,668,655 patient records with drug-adverse reactions, was analyzed. The disproportionality analysis was used to calculate the reporting odds ratios (ROR) with 95% confidence intervals (CI) to predict HCQ-associated CV-AEs. HCQ was associated with higher reporting of right ventricular hypertrophy (ROR: 6.68; 95% CI: 4.02 to 11.17), left ventricular hypertrophy (ROR: 3.81; 95% CI: 2.57 to 5.66), diastolic dysfunction (ROR: 3.54; 95% CI: 2.19 to 5.71), pericarditis (ROR: 3.09; 95% CI: 2.27 to 4.23), torsades de pointes (TdP) (ROR: 3.05; 95% CI: 2.30 to 4.10), congestive cardiomyopathy (ROR: 2.98; 95% CI: 2.01 to 4.42), ejection fraction decreased (ROR: 2.41; 95% CI: 1.80 to 3.22), right ventricular failure (ROR: 2.40; 95% CI: 1.64 to 3.50), atrioventricular block complete (ROR: 2.30; 95% CI: 1.55 to 3.41) and QT prolongation (ROR: 2.09; 95% CI: 1.74 to 2.52). QT prolongation and TdP are most relevant to the COVID-19 treatment regimen of high doses for a comparatively short period and represent the most common HCQ-associated AEs. The patients receiving HCQ are at higher risk of various cardiac AEs, including QT prolongation and TdP. These findings highlight the urgent need for prospective, randomized, controlled studies to assess the risk/benefit ratio of HCQ in the COVID-19 setting before its widespread adoption as therapy.


Abstract. We document and evaluate the aerosol schemes as implemented in the physical and Earth system models, the Global Coupled 3.1 configuration of the Hadley Centre Global Environment Model version 3 (HadGEM3-GC3.1)
and the United Kingdom Earth System Model (UKESM1), which are contributing to the sixth Coupled Model Intercomparison Project (CMIP6).
The simulation of aerosols in the present-day period of the historical ensemble of these models is evaluated
against a range of observations.
Updates to the aerosol microphysics scheme are documented as well as differences in the
aerosol representation between the physical and Earth system configurations.
The additional Earth system interactions included in UKESM1 lead to differences in the emissions of
natural aerosol sources such as dimethyl sulfide, mineral dust and organic aerosol and subsequent evolution
of these species in the model.
UKESM1 also includes a stratospheric–tropospheric chemistry scheme which is fully coupled to the aerosol scheme,
while GC3.1 employs a simplified aerosol chemistry mechanism driven by prescribed monthly climatologies of
the relevant oxidants.
Overall, the simulated speciated aerosol mass concentrations compare reasonably well with observations.
Both models capture the negative trend in sulfate aerosol concentrations over Europe and the eastern United
States of America (US)
although the models tend to underestimate sulfate concentrations in both regions.
Interactive emissions of biogenic volatile organic compounds in UKESM1 lead
to an improved agreement of organic aerosol over the US.
Simulated dust burdens are similar in both models despite a 2-fold difference in dust emissions.
Aerosol optical depth is biased low in dust source and outflow regions but performs well in
other regions compared to a number of satellite and ground-based retrievals of aerosol optical depth.
Simulated aerosol number concentrations are generally within a factor of 2 of the observations, with
both models tending to overestimate number concentrations over remote ocean regions, apart from
at high latitudes, and underestimate over Northern Hemisphere continents.
Finally, a new primary marine organic aerosol source is implemented in UKESM1 for the first time.
The impact of this new aerosol source is evaluated. Over the pristine Southern Ocean, it is found to improve the seasonal
cycle of organic aerosol mass and cloud droplet number concentrations relative to GC3.1
although underestimations in cloud droplet number concentrations remain.
This paper provides a useful characterisation of the aerosol climatology in both models
and will facilitate understanding in the numerous aerosol–climate interaction studies that will
be conducted as part of CMIP6 and beyond.