3,131 research outputs found

    Coherent Structures in Fluids are Topological Torsion Defects

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    Abstract: Cartan’s theoryofaglobal1-formofActiononaprojectivevarietypermitsthe algebraicevaluationof certainusefulgeometricandtopologicalobjectswhichcanbe singular. Theprojectivealgebraicmethodsthereforel ndthemselvestothedevelopmentof a theoryof coherentstructuresanddefectsin whichtheconceptof translationalshear dislocationsandrotationalsheardisclinationscanbeputonequalfooting. Thetopological methodsnotonlyleadto a precisedefinitionof coherentstructuresin fluids, butalso produceanon-statisticaltestforthermodynamicirreversibilityonasymplecticmanifoldof dimension4, andthereforeyieldanecessarycriteriaforturbulence. 1

    The fundamental problem of command : plan and compliance in a partially centralised economy

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    When a principal gives an order to an agent and advances resources for its implementation, the temptations for the agent to shirk or steal from the principal rather than comply constitute the fundamental problem of command. Historically, partially centralised command economies enforced compliance in various ways, assisted by nesting the fundamental problem of exchange within that of command. The Soviet economy provides some relevant data. The Soviet command system combined several enforcement mechanisms in an equilibrium that shifted as agents learned and each mechanism's comparative costs and benefits changed. When the conditions for an equilibrium disappeared, the system collapsed.Comparative Economic Studies (2005) 47, 296–314. doi:10.1057/palgrave.ces.810011

    30 days wild: development and evaluation of a large-scale nature engagement campaign to improve well-being

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    There is a need to increase people’s engagement with and connection to nature, both for human well-being and the conservation of nature itself. In order to suggest ways for people to engage with nature and create a wider social context to normalise nature engagement, The Wildlife Trusts developed a mass engagement campaign, 30 Days Wild. The campaign asked people to engage with nature every day for a month. 12,400 people signed up for 30 Days Wild via an online sign-up with an estimated 18,500 taking part overall, resulting in an estimated 300,000 engagements with nature by participants. Samples of those taking part were found to have sustained increases in happiness, health, connection to nature and pro-nature behaviours. With the improvement in health being predicted by the improvement in happiness, this relationship was mediated by the change in connection to nature

    Depression diagnoses following the identification of bipolar disorder: costly incongruent diagnoses

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    <p>Abstract</p> <p>Background</p> <p>Previous research has documented that the symptoms of bipolar disorder are often mistaken for unipolar depression prior to a patient's first bipolar diagnosis. The assumption has been that once a patient receives a bipolar diagnosis they will no longer be given a misdiagnosis of depression. The objectives of this study were 1) to assess the rate of subsequent unipolar depression diagnosis in individuals with a history of bipolar disorder and 2) to assess the increased cost associated with this potential misdiagnosis.</p> <p>Methods</p> <p>This study utilized a retrospective cohort design using administrative claims data from 2002 and 2003. Patient inclusion criteria for the study were 1) at least 2 bipolar diagnoses in 2002, 2) continuous enrollment during 2002 and 2003, 3) a pharmacy benefit, and 4) age 18 to 64. Patients with at least 2 unipolar depression diagnoses in 2003 were categorized as having an incongruent diagnosis of unipolar depression. We used propensity scoring to control for selection bias. Utilization was evaluated using negative binomial models. We evaluated cost differences between patient cohorts using generalized linear models.</p> <p>Results</p> <p>Of the 7981 patients who met all inclusion criteria for the analysis, 17.5% (1400) had an incongruent depression diagnosis (IDD). After controlling for background differences, individuals who received an IDD had higher rates of inpatient and outpatient psychiatric utilization and cost, on average, an additional $1641 per year compared to individuals without an IDD.</p> <p>Conclusions</p> <p>A strikingly high proportion of bipolar patients are given the differential diagnosis of unipolar depression <it>after </it>being identified as having bipolar disorder. Individuals with an IDD had increased acute psychiatric care services, suggesting higher levels of relapses, and were at risk for inappropriate treatment, as antidepressant therapy without a concomitant mood-stabilizing medication is contraindicated in bipolar disorder. Further prospective research is needed to validate the findings from this retrospective administrative claims-based analysis.</p

    Cardiorespiratory fitness, fatness and the acute blood pressure response to exercise in adolescence

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    Objective: Exaggerated exercise blood pressure (BP) is associated with cardiovascular risk factors in adolescence. Cardiorespiratory fitness and adiposity (fatness) areindependent contributors to cardiovascular risk, but their interrelated associationswith exercise BP are unknown. This study aimed to determine the relationships between fitness, fatness, and the acute BP response to exercise in a large birth cohort ofadolescents.Methods: 2292 adolescents from the Avon Longitudinal Study of Parents andChildren (aged 17.8 ± 0.4 years, 38.5% male) completed a sub-maximal exercisestep test that allowed fitness (VO2 max) to be determined from workload and heart rateusing a validated equation. Exercise BP was measured immediately on test cessationand fatness calculated as the ratio of total fat mass to total body mass measured byDXA.Results: Post-exercise systolic BP decreased stepwise with tertile of fitness (146(18); 142 (17); 141 (16) mmHg) but increased with tertile of fatness (138 (15); 142(16); 149 (18) mmHg). In separate models, fitness and fatness were associated withpost-exercise systolic BP adjusted for sex, age, height, smoking, and socioeconomicstatus (standardized β: −1.80, 95%CI: −2.64, −0.95 mmHg/SD and 4.31, 95%CI:3.49, 5.13 mmHg/SD). However, when fitness and fatness were included in thesame model, only fatness remained associated with exercise BP (4.65, 95%CI: 3.69,5.61 mmHg/SD).Conclusion: Both fitness and fatness are associated with the acute BP response to exercise in adolescence. The fitness-exercise BP association was not independent of fatness, implying the cardiovascular protective effects of cardiorespiratory fitness mayonly be realized with more favorable body composition

    Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage.

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    Colibactin is an assumed human gut bacterial genotoxin, whose biosynthesis is linked to the clb genomic island that has a widespread distribution in pathogenic and commensal human enterobacteria. Colibactin-producing gut microbes promote colon tumour formation and enhance the progression of colorectal cancer via cellular senescence and death induced by DNA double-strand breaks (DSBs); however, the chemical basis that contributes to the pathogenesis at the molecular level has not been fully characterized. Here, we report the discovery of colibactin-645, a macrocyclic colibactin metabolite that recapitulates the previously assumed genotoxicity and cytotoxicity. Colibactin-645 shows strong DNA DSB activity in vitro and in human cell cultures via a unique copper-mediated oxidative mechanism. We also delineate a complete biosynthetic model for colibactin-645, which highlights a unique fate of the aminomalonate-building monomer in forming the C-terminal 5-hydroxy-4-oxazolecarboxylic acid moiety through the activities of both the polyketide synthase ClbO and the amidase ClbL. This work thus provides a molecular basis for colibactin's DNA DSB activity and facilitates further mechanistic study of colibactin-related colorectal cancer incidence and prevention

    Conventional and CT angiography in children: dosimetry and dose comparisons

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    Tremendous advances have been made in imaging in children with both congenital and acquired heart disease. These include technical advances in cardiac catheterization and conventional angiography, especially with advancements in interventional procedures, as well as noninvasive imaging with MR and CT angiography. With rapid advances in multidetector CT (MDCT) technology, most recently 64-detector array systems (64-slice MDCT), have come a number of advantages over MR. However, both conventional and CT angiography impart radiation dose to children. Although the presence of radiation exposure to children has long been recognized, it is apparent that our ability to assess this dose, particularly in light of the rapid advancements, has been limited. Traditional methods of dosimetry for both conventional and CT angiography are somewhat cumbersome or involve a potential for substantial uncertainty. Recent developments in dosimetry, including metal oxide semiconductor field effect transistors (MOSFET) and the availability of anthropomorphic, tissue-equivalent phantoms have provided new opportunities for dosimetric assessments. Recent work with this technology in state-of-the-art cardiac angiography suites as well as with MDCT have offered direct comparisons of doses in infants and children undergoing diagnostic cardiac evaluation. It is with these dose data that assessment of risks, and ultimately the assessment of risk-benefit, can be better achieved

    Role of the mesoamygdaloid dopamine projection in emotional learning

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    Amygdala dopamine is crucially involved in the acquisition of Pavlovian associations, as measured via conditioned approach to the location of the unconditioned stimulus (US). However, learning begins before skeletomotor output, so this study assessed whether amygdala dopamine is also involved in earlier 'emotional' learning. A variant of the conditioned reinforcement (CR) procedure was validated where training was restricted to curtail the development of selective conditioned approach to the US location, and effects of amygdala dopamine manipulations before training or later CR testing assessed. Experiment 1a presented a light paired (CS+ group) or unpaired (CS- group) with a US. There were 1, 2 or 10 sessions, 4 trials per session. Then, the US was removed, and two novel levers presented. One lever (CR+) presented the light, and lever pressing was recorded. Experiment 1b also included a tone stimulus. Experiment 2 applied intra-amygdala R(+) 7-OH-DPAT (10 nmol/1.0 A mu l/side) before two training sessions (Experiment 2a) or a CR session (Experiment 2b). For Experiments 1a and 1b, the CS+ group preferred the CR+ lever across all sessions. Conditioned alcove approach during 1 or 2 training sessions or associated CR tests was low and nonspecific. In Experiment 2a, R(+) 7-OH-DPAT before training greatly diminished lever pressing during a subsequent CR test, preferentially on the CR+ lever. For Experiment 2b, R(+) 7-OH-DPAT infusions before the CR test also reduced lever pressing. Manipulations of amygdala dopamine impact the earliest stage of learning in which emotional reactions may be most prevalent
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