2,369 research outputs found
A non-exercise method to determine cardiorespiratory fitness identifies females predicted to be at 'high risk of type 2 diabetes
Detecting a Currency's Dominance or Dependence using Foreign Exchange Network Trees
In a system containing a large number of interacting stochastic processes,
there will typically be many non-zero correlation coefficients. This makes it
difficult to either visualize the system's inter-dependencies, or identify its
dominant elements. Such a situation arises in Foreign Exchange (FX) which is
the world's biggest market. Here we develop a network analysis of these
correlations using Minimum Spanning Trees (MSTs). We show that not only do the
MSTs provide a meaningful representation of the global FX dynamics, but they
also enable one to determine momentarily dominant and dependent currencies. We
find that information about a country's geographical ties emerges from the raw
exchange-rate data. Most importantly from a trading perspective, we discuss how
to infer which currencies are `in play' during a particular period of time
Estimating exclusion: a tool to help designers
An exclusion audit assesses how inclusive a product or service is. This is useful for
comparing designs and identifying points for improvement. In an exclusion audit, the
designer or usability expert identifies the demands a product places on the user‟s
capabilities and enters these into an exclusion calculator. This software then estimates
the proportion of the adult British population who would be excluded from using the
product because their capabilities do not meet these demands.
This paper describes research on improving the exclusion calculator based on a
recent reanalysis of the calculator‟s underlying dataset. This enabled the capabilities to
be broken down into more specific sub-categories or “demand types”. An experiment
investigated the use of these demand types in the context of an exclusion audit. It found
that participants could determine the demand type of an action consistently, in the
majority of cases. This approach was adopted in a redesign of the calculator, described
in this paper
Impact of Unexpected Events, Shocking News and Rumours on Foreign Exchange Market Dynamics
We analyze the dynamical response of the world's financial community to
various types of unexpected events, including the 9/11 terrorist attacks as
they unfolded on a minute-by-minute basis. We find that there are various
'species' of news, characterized by how quickly the news get absorbed, how much
meaning and importance is assigned to it by the community, and what subsequent
actions are then taken. For example, the response to the unfolding events of
9/11 shows a gradual collective understanding of what was happening, rather
than an immediate realization. For news items which are not simple economic
statements, and hence whose implications are not immediately obvious, we
uncover periods of collective discovery during which collective opinions seem
to oscillate in a remarkably synchronized way. In the case of a rumour, our
findings also provide a concrete example of contagion in inter-connected
communities. Practical applications of this work include the possibility of
producing selective newsfeeds for specific communities, based on their likely
impact
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A randomised controlled trial of cognitive behavioural treatment for obsessive compulsive disorder in children and adolescents
Cognitive behaviour therapy (CBT) for young people with obsessive compulsive disorder (OCD) has become the treatment of first choice. However, the literature is largely based on studies emphasising exposure and response prevention. In this study, we report on a randomised controlled trial of CBT for young people carried out in typical outpatient clinic conditions which focused on cognitions. A randomised controlled trial compares 10 sessions of manualised cognitive behavioural treatment with a 12-week waiting list for adolescents and children with OCD. Assessors were blind to treatment allocation. 21 consecutive patients with OCD aged between 9 and 18 years were recruited. The group who received treatment improved more than a comparison group who waited for 3 months. The second group was treated subsequently using the same protocol and made similar gains. In conclusion, CBT can be delivered effectively to young people with OCD in typical outpatient settings
Conflict of interest and signal interference lead to the breakdown of honest signalling
Animals use signals to coordinate a wide range of behaviours, from feeding offspring to predator avoidance. This poses an evolutionary problem, because individuals could potentially signal dishonestly to coerce others into behaving in ways that benefit the signaller. Theory suggests that honest signalling is favoured when individuals share a common interest and signals carry reliable information. Here, we exploit the opportunities offered by bacterial signalling, to test these predictions with an experimental evolution approach. We show that: (1) a reduced relatedness leads to the relative breakdown of signalling; (2) signalling breaks down by the invasion of mutants that show both reduced signalling and reduced response to signal; (3) the genetic route to signalling breakdown is variable; (4) the addition of artificial signal, to interfere with signal information, also leads to reduced signalling. Our results provide clear support for signalling theory, but we did not find evidence for the previously predicted coercion at intermediate relatedness, suggesting that mechanistic details can alter the qualitative nature of specific predictions. Furthermore, populations evolved under low relatedness caused less mortality to insect hosts, showing how signal evolution in bacterial pathogens can drive the evolution of virulence in the opposite direction to that often predicted by theory
Abatacept Pharmacokinetics and Exposure Response in Patients Hospitalized With COVID-19: A Secondary Analysis of the ACTIV-1 IM Randomized Clinical Trial
IMPORTANCE: The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown.
OBJECTIVE: To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments.
DESIGN, SETTING, AND PARTICIPANTS: This study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021. The trial included hospitalized adults who received abatacept in addition to standard of care for treatment of COVID-19 pneumonia. Data analysis was performed between September 2022 and February 2024.
EXPOSURE: Single intravenous infusion of abatacept (10 mg/kg with a maximum dose of 1000 mg).
MAIN OUTCOMES AND MEASURES: Mortality at day 28 was the primary outcome of interest, and time to recovery at day 28 was the secondary outcome. Drug exposure was assessed using the projected area under the serum concentration time curve over 28 days (AUC0-28). Logistic regression modeling was used to analyze the association between drug exposure and 28-day mortality, adjusted for age, sex, and disease severity. The association between time to recovery and abatacept exposure was examined using Fine-Gray modeling with death as a competing risk, and was adjusted for age, sex, and disease severity.
RESULTS: Of the 509 patients who received abatacept, 395 patients with 848 serum samples were included in the population pharmacokinetic analysis. Their median age was 55 (range, 19-89) years and most (250 [63.3%]) were men. Abatacept clearance increased with body weight and more severe disease activity at baseline. Drug exposure was higher in patients who survived vs those who died, with a median AUC0-28 of 21 428 (range, 8462-43 378) mg × h/L vs 18 262 (range, 9628-27 507) mg × h/L (P \u3c .001). Controlling for age, sex, and disease severity, an increase of 5000 units in AUC0-28 was associated with lower odds of mortality at day 28 (OR, 0.52 [95% CI, 0.35-0.79]; P = .002). For an AUC0-28 of 19 400 mg × h/L or less, there was a higher probability of recovery at day 28 (hazard ratio, 2.63 [95% CI, 1.70-4.08] for every 5000-unit increase; P \u3c .001). Controlling for age, sex, and disease severity, every 5000-unit increase in AUC0-28 was also associated with lower odds of a composite safety event at 28 days (OR, 0.46 [95% CI, 0.33-0.63]; P \u3c .001). Using the dosing regimen studied in the ACTIV-1 IM trial, 121 of the 395 patients (30.6%) would not achieve an abatacept exposure of at least 19 400 mg × h/L, particularly at the extremes of body weight. Using a modified, higher-dose regimen, only 12 patients (3.0%) would not achieve the hypothesized target abatacept exposure.
CONCLUSIONS AND RELEVANCE: In this study, patients who were hospitalized with severe COVID-19 and achieved higher projected abatacept exposure had reduced mortality and a higher probability of recovery with fewer safety events. However, abatacept clearance was high in this population, and the current abatacept dosing (10 mg/kg intravenously with a maximum of 1000 mg) may not achieve optimal exposure in all patients.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04593940
Conflict of interest and signal interference lead to the breakdown of honest signalling
Animals use signals to coordinate a wide range of behaviours, from feeding offspring to predator avoidance. This poses an evolutionary problem, because individuals could potentially signal dishonestly to coerce others into behaving in ways that benefit the signaller. Theory suggests that honest signalling is favoured when individuals share a common interest and signals carry reliable information. Here, we exploit the opportunities offered by bacterial signalling, to test these predictions with an experimental evolution approach. We show that: (1) a reduced relatedness leads to the relative breakdown of signalling; (2) signalling breaks down by the invasion of mutants that show both reduced signalling and reduced response to signal; (3) the genetic route to signalling breakdown is variable; (4) the addition of artificial signal, to interfere with signal information, also leads to reduced signalling. Our results provide clear support for signalling theory, but we did not find evidence for the previously predicted coercion at intermediate relatedness, suggesting that mechanistic details can alter the qualitative nature of specific predictions. Furthermore, populations evolved under low relatedness caused less mortality to insect hosts, showing how signal evolution in bacterial pathogens can drive the evolution of virulence in the opposite direction to that often predicted by theory
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