1,237 research outputs found

    Complex Derivatives

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    The intrinsic complexity of the financial derivatives market has emerged as both an incentive to engage in it, and a key source of its inherent instability. Regulators now faced with the challenge of taming this beast may find inspiration in the budding science of complex systems. When financial derivatives were cast in 2002 as latent 'weapons of mass destruction', one might have expected the world at large to sit up and listen — particularly in the wake of subsequent events that led to the financial crisis of 2008. Instead, the derivatives market continues to grow in size and complexity (Fig. 1), spawning a new generation of financial innovations, and raising concerns about its potential impact on the economy as a whole. A derivative instrument is a financial contract between two parties, in which the value of the payoff is derived from the value of another financial instrument or asset, called the underlying entity. In some cases, this contract acts as a kind of insurance: in a credit default swap, for example, a lender might buy protection from a third party to insure against the default of the borrower. However, unlike conventional insurance, in which a person necessarily owns the house she wants to insure, derivatives can be negotiated on any underlying entity — meaning anyone could take out insurance on the house in question. Speculation therefore emerges as another reason to trade in derivatives. By engaging in a speculative derivatives market, players can potentially amplify their gains, which is arguably the most plausible explanation for the proliferation of derivatives in recent years. Needless to say, losses are also amplified. Unlike bets on, say, dice — where the chances of the outcome are not affected by the bet itself — the more market players bet on the default of a country, the more likely the default becomes. Eventually the game becomes a self-fulfilling prophecy, as in a bank run, where if each party believes that others will withdraw their money from the bank, it pays each to do so. More perversely, in some cases parties have incentives (and opportunities) to precipitate these events, by spreading rumours or by manipulating the prices on which the derivatives are contingent — a situation seen most recently in the London Interbank Offered Rate (LIBOR) affair. Proponents of derivatives have long argued that these instruments help to stabilize markets by distributing risk, but it has been shown recently that in many situations risk sharing can also lead to instabilities

    Neuromodulation of innate immunity by remote ischaemic conditioning in humans: Experimental cross-over study.

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    Experimental animal studies on the mechanisms of remote ischaemic conditioning (RIC)-induced cardioprotection against ischaemia/reperfusion injury demonstrate involvement of both neuronal and humoral pathways. Autonomic parasympathetic (vagal) pathways confer organ protection through both direct innervation and/or immunomodulation, but evidence in humans is lacking. During acute inflammation, vagal release of acetylcholine suppresses CD11b expression, a critical β2-integrin regulating neutrophil adhesion to the endothelium and transmigration to sites of injury. Here, we tested the hypothesis that RIC recruits vagal activity in humans and has an anti-inflammatory effect by reducing neutrophil CD11b expression. Participants (age:50 ​± ​19 years; 53% female) underwent ultrasound-guided injection of local anaesthetic within the brachial plexus before applying 3 ​× ​8 min cycles of brachial artery occlusion using a blood pressure cuff (RICblock). RIC was repeated 6 weeks later without brachial plexus block. Masked analysers quantified vagal activity (heart rate, heart rate variability (HRV)) before, and 10 ​min after, the last cycle of RIC. RR-interval increased after RIC (reduced heart rate) by 40 ​ms (95% confidence intervals (95%CI):13-66; n ​= ​17 subjects; P ​= ​0.003). RR-interval did not change after brachial plexus blockade (mean difference: 20 ​ms (95%CI:-11 to 50); P ​= ​0.19). The high-frequency component of HRV was reduced after RICblock, but remained unchanged after RIC (P ​< ​0.001), indicating that RIC preserved vagal activity. LPS-induced CD16+CD11b+ expression in whole blood (measured by flow cytometry) was reduced by RIC (3615 median fluorescence units (95%CI:475-6754); P = 0.026), compared with 2331 units (95%CI:-3921 to 8582); P = 0.726) after RICblock. These data suggest that in humans RIC recruits vagal cardiac and anti-inflammatory mechanisms via ischaemia/reperfusion-induced activation of sensory nerve fibres that innervate the organ undergoing RIC

    The transition towards a sustainable energy system in Europe: What role can North Africa's solar resources play?

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    Securing energy supply and speeding up the transition towards a reliable, sustainable, low-carbon energy system are among the major current and future challenges facing Europe. Importing dispatchable solar electricity from North Africa is considered as a potential and attractive option. Nevertheless, as things currently stand, the European Commission focuses mainly on the exploitation of the existing wind power potential in the North Sea, largely ignoring the solar power potential in the Sahara region of North Africa. After discussing the major challenges and issues facing Europe to achieve the assigned ambitious objectives, the paper emphasises the importance of North Africa's solar resources in helping Europe to successfully address the challenge of decarbonising its electricity system, in particular with regards to the security of supply and sustainability. Within these two major challenges, the paper explores the issues of access, barriers and opportunities. The paper highlights why the EU’s energy and climate goals will not be achievable without adequate grid expansion and grid-scale energy storage facilities, as well as other innovative measures to manage demand and ensure a secure energy supply. In this respect, the paper shows how the import of dispatchable electricity from North Africa via specific HVDC links could play a key role in helping the EU achieve its energy targets in a cost effective way without recourse to significant investments in transmission infrastructure and storage facilities. The paper then attempts to identify and analyze the main barriers that continue to inhibit the export of solar electricity from North Africa to Europe. Finally, to make the project more attractive and achievable in the near future, the paper proposes a systematic approach for setting up energy import scenarios. A promising import scenario is presented where energy import via Italy is shown to be a more viable and effective solution than via Spain.Peer reviewe

    Physical Activity during Cancer Treatment (PACT) Study: design of a randomised clinical trial

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    <p>Abstract</p> <p>Background</p> <p>Fatigue is a major problem of cancer patients. Thirty percent of cancer survivors report serious fatigue three years after finishing treatment. There is evidence that physical exercise during cancer treatment reduces fatigue. This may also lead to an improvement of quality of life. Such findings may result in a decrease of healthcare related expenditures and societal costs due to sick leave. However, no studies are known that investigated these hypotheses. Therefore, the primary aim of our study is to assess the effect of exercise during cancer treatment on reducing complaints of fatigue and on reducing health service utilisation and sick leave.</p> <p>Methods/Design</p> <p>The Physical Activity during Cancer Treatment study is a multicentre randomised controlled trial in 150 breast and 150 colon cancer patients undergoing cancer treatment. Participants will be randomised to an exercise or a control group. In addition to the usual care, the exercise group will participate in an 18-week supervised group exercise programme. The control group will be asked to maintain their habitual physical activity pattern. Study endpoints will be assessed after 18 weeks (short term) and after 9 months (long term). Validated questionnaires will be used. Primary outcome: fatigue (Multidimensional Fatigue Inventory and Fatigue Quality List) and cost-effectiveness, health service utilisation and sick leave. Secondary outcome: health related quality of life (European Organisation Research and Treatment of Cancer-Quality of Life questionnaire-C30, Short Form 36 healthy survey), impact on functioning and autonomy (Impact on functioning and autonomy questionnaire), anxiety and depression (Hospital Anxiety and Depression Scale), physical fitness (aerobic peak capacity, muscle strength), body composition and cognitive-behavioural aspects. To register health service utilisation and sick leave, participants will keep diaries including the EuroQuol-5D. Physical activity level will be measured using the Short Questionnaire to Assess Health-Enhancing Physical Activity and will be monitored with an exercise log and a pedometer.</p> <p>Discussion</p> <p>This study investigates the (cost)-effectiveness of exercise during adjuvant treatment of patients with breast or colon cancer. If early physical exercise proves to be (cost) effective, establishing standardised physical exercise programmes during cancer treatment will be planned.</p> <p>Trial registration</p> <p>Current Controlled trials ISRCTN43801571, Dutch Trial Register NTR2138</p

    The C-Terminal Domain of the Arabinosyltransferase Mycobacterium tuberculosis EmbC Is a Lectin-Like Carbohydrate Binding Module

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    The D-arabinan-containing polymers arabinogalactan (AG) and lipoarabinomannan (LAM) are essential components of the unique cell envelope of the pathogen Mycobacterium tuberculosis. Biosynthesis of AG and LAM involves a series of membrane-embedded arabinofuranosyl (Araf) transferases whose structures are largely uncharacterised, despite the fact that several of them are pharmacological targets of ethambutol, a frontline drug in tuberculosis therapy. Herein, we present the crystal structure of the C-terminal hydrophilic domain of the ethambutol-sensitive Araf transferase M. tuberculosis EmbC, which is essential for LAM synthesis. The structure of the C-terminal domain of EmbC (EmbCCT) encompasses two sub-domains of different folds, of which subdomain II shows distinct similarity to lectin-like carbohydrate-binding modules (CBM). Co-crystallisation with a cell wall-derived di-arabinoside acceptor analogue and structural comparison with ligand-bound CBMs suggest that EmbCCT contains two separate carbohydrate binding sites, associated with subdomains I and II, respectively. Single-residue substitution of conserved tryptophan residues (Trp868, Trp985) at these respective sites inhibited EmbC-catalysed extension of LAM. The same substitutions differentially abrogated binding of di- and penta-arabinofuranoside acceptor analogues to EmbCCT, linking the loss of activity to compromised acceptor substrate binding, indicating the presence of two separate carbohydrate binding sites, and demonstrating that subdomain II indeed functions as a carbohydrate-binding module. This work provides the first step towards unravelling the structure and function of a GT-C-type glycosyltransferase that is essential in M. tuberculosis. Author Summary Top Tuberculosis (TB), an infectious disease caused by the bacillus Mycobacterium tuberculosis, burdens large swaths of the world population. Treatment of active TB typically requires administration of an antibiotic cocktail over several months that includes the drug ethambutol. This front line compound inhibits a set of arabinosyltransferase enzymes, called EmbA, EmbB and EmbC, which are critical for the synthesis of arabinan, a vital polysaccharide in the pathogen's unique cell envelope. How precisely ethambutol inhibits arabinosyltransferase activity is not clear, in part because structural information of its pharmacological targets has been elusive. Here, we report the high-resolution structure of the C-terminal domain of the ethambutol-target EmbC, a 390-amino acid fragment responsible for acceptor substrate recognition. Combining the X-ray crystallographic analysis with structural comparisons, site-directed mutagenesis, activity and ligand binding assays, we identified two regions in the C-terminal domain of EmbC that are capable of binding acceptor substrate mimics and are critical for activity of the full-length enzyme. Our results begin to define structure-function relationships in a family of structurally uncharacterised membrane-embedded glycosyltransferases, which are an important target for tuberculosis therapy

    The Heart of the Matter. About Good Nursing and Telecare

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    Nurses and ethicists worry that the implementation of care at a distance or telecare will impoverish patient care by taking out ‘the heart’ of the clinical work. This means that telecare is feared to induce the neglect of patients, and to possibly hinder the development of a personal relation between nurse and patient. This study aims to analyse whether these worries are warranted by analysing Dutch care practices using telemonitoring in care for chronic patients in the Netherlands. How do clinical practices of nursing change when telecare devices are introduced and what this means for notions and norms of good nursing? The paper concludes that at this point the practices studied do not warrant the fear of negligence and compromised relations. Quite the contrary; in the practices studied, telecare lead to more frequent and more specialised contacts between nurses and patients. The paper concludes by reflecting on the ethical implications of these changes

    Occupational performance of the primary schoolchildren with special education needs in Malaysia: exploring the needs of school-based therapy service

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    Children’s occupational performance are activities of daily living, play/ leisure, social participation, education, and work. In developed countries, school-based therapy services are being provided for schoolchildren with special needs. The importance of these services in Malaysia is timely to be explored. This exploratory cross-sectional study identified occupational performance levels of primary schoolchildren with special needs in integrated special education programmes in Malaysia; children with intellectual disability, autism, attention deficit hyperactive disorder, Down syndrome, speech impairment, visual impairment, hearing impairment, and specific learning disorder. Researchers conducted Motor-Free Visual Perceptual Test Third Edition (MVPT-3), Beery-Buktenica Developmental Test of Visual-Motor Integration Fifth Edition (Beery-VMI), Test of Gross Motor Development – 2 (TGMD-2), Test of Hand Writing Skills-Revised (THS-R), and School Function Assessment (SFA) for 121 students. Results showed that 69.5% of the students scored very low to low average in MVPT-3 (median standard score = 70.0, Std. IQR = 37); 69.4% were very low to below average in Beery-VMI (mean standard score = 78.8, Std. deviation = 20.5); 73% were below age level raw score in TGMD-2; 72.8% were below average in THS-R (median standard score = 74.0, Std. IQR = 27.0); and 81% were below the criterion cut-off in school function. The children with below-normal MVPT, VMI, TGMD2, and THS scores, compared to the children with normal scores for these tests had significantly lower scores (p < 0.001). All the students had impairment in occupation performance at least in one area. This study recommends school-based occupational therapy and other rehabilitation services in the school system in Malaysia

    A First- and Second-Order Motion Energy Analysis of Peripheral Motion Illusions Leads to Further Evidence of “Feature Blur” in Peripheral Vision

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    Anatomical and physiological differences between the central and peripheral visual systems are well documented. Recent findings have suggested that vision in the periphery is not just a scaled version of foveal vision, but rather is relatively poor at representing spatial and temporal phase and other visual features. Shapiro, Lu, Huang, Knight, and Ennis (2010) have recently examined a motion stimulus (the “curveball illusion”) in which the shift from foveal to peripheral viewing results in a dramatic spatial/temporal discontinuity. Here, we apply a similar analysis to a range of other spatial/temporal configurations that create perceptual conflict between foveal and peripheral vision.To elucidate how the differences between foveal and peripheral vision affect super-threshold vision, we created a series of complex visual displays that contain opposing sources of motion information. The displays (referred to as the peripheral escalator illusion, peripheral acceleration and deceleration illusions, rotating reversals illusion, and disappearing squares illusion) create dramatically different perceptions when viewed foveally versus peripherally. We compute the first-order and second-order directional motion energy available in the displays using a three-dimensional Fourier analysis in the (x, y, t) space. The peripheral escalator, acceleration and deceleration illusions and rotating reversals illusion all show a similar trend: in the fovea, the first-order motion energy and second-order motion energy can be perceptually separated from each other; in the periphery, the perception seems to correspond to a combination of the multiple sources of motion information. The disappearing squares illusion shows that the ability to assemble the features of Kanisza squares becomes slower in the periphery.The results lead us to hypothesize “feature blur” in the periphery (i.e., the peripheral visual system combines features that the foveal visual system can separate). Feature blur is of general importance because humans are frequently bringing the information in the periphery to the fovea and vice versa

    Aerobic Exercise during Pregnancy and Presence of Fetal-Maternal Heart Rate Synchronization

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    It has been shown that short-term direct interaction between maternal and fetal heart rates may take place and that this interaction is affected by the rate of maternal respiration. The aim of this study was to determine the effect of maternal aerobic exercise during pregnancy on the occurrence of fetal-maternal heart rate synchronization.In 40 pregnant women at the 36th week of gestation, 21 of whom exercised regularly, we acquired 18 min. RR interval time series obtained simultaneously in the mothers and their fetuses from magnetocardiographic recordings. The time series of the two groups were examined with respect to their heart rate variability, the maternal respiratory rate and the presence of synchronization epochs as determined on the basis of synchrograms. Surrogate data were used to assess whether the occurrence of synchronization was due to chance.In the original data, we found synchronization occurred less often in pregnancies in which the mothers had exercised regularly. These subjects also displayed higher combined fetal-maternal heart rate variability and lower maternal respiratory rates. Analysis of the surrogate data showed shorter epochs of synchronization and a lack of the phase coordination found between maternal and fetal beat timing in the original data.The results suggest that fetal-maternal heart rate coupling is present but generally weak. Maternal exercise has a damping effect on its occurrence, most likely due to an increase in beat-to-beat differences, higher vagal tone and slower breathing rates

    Improved Algorithms for the Approximate k-List Problem in Euclidean Norm

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    We present an algorithm for the approximate kk-List problem for the Euclidean distance that improves upon the Bai-Laarhoven-Stehle (BLS) algorithm from ANTS\u2716. The improvement stems from the observation that almost all the solutions to the approximate kk-List problem form a particular configuration in nn-dimensional space. Due to special properties of configurations, it is much easier to verify whether a kk-tuple forms a configuration rather than checking whether it gives a solution to the kk-List problem. Thus, phrasing the kk-List problem as a problem of finding such configurations immediately gives a better algorithm. Furthermore, the search for configurations can be sped up using techniques from Locality-Sensitive Hashing (LSH). Stated in terms of configuration-search, our LSH-like algorithm offers a broader picture on previous LSH algorithms. For the Shortest Vector Problem, our configuration-search algorithm results in an exponential improvement for memory-efficient sieving algorithms. For k=3k=3, it allows us to bring down the complexity of the BLS sieve algorithm on an nn-dimensional lattice from 20.4812n+o(n)2^{0.4812n+o(n)} to 20.3962n+o(n)2^{0.3962n + o(n)} with the same space-requirement 20.1887n+o(n)2^{0.1887n + o(n)}. Note that our algorithm beats the Gauss Sieve algorithm with time resp. space requirements of 20.415n+o(n)2^{0.415n+o(n)} resp. 20.208n+o(n)2^{0.208n + o(n)}, while being easy to implement. Using LSH techniques, we can further reduce the time complexity down to 20.3717n+o(n)2^{0.3717n + o(n)} while retaining a memory complexity of 20.1887n+o(n)2^{0.1887n+o(n)}
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