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Biomarker-guided antibiotic duration for hospitalized patients with suspected sepsis: the ADAPT-sepsis randomized clinical trial
Get PDFImportance: For hospitalized critically ill adults with suspected sepsis, procalcitonin (PCT) and C-reactive protein (CRP) monitoring protocols can guide the duration of antibiotic therapy, but the evidence of the effect and safety of these protocols remains uncertain.
Objective: To determine whether decisions based on assessment of CRP or PCT safely results in a reduction in the duration of antibiotic therapy.
Design, Setting, and Participants: A multicenter, intervention-concealed randomized clinical trial, involving 2760 adults (≥18 years), in 41 UK National Health Service (NHS) intensive care units, requiring critical care within 24 hours of initiating intravenous antibiotics for suspected sepsis and likely to continue antibiotics for at least 72 hours.
Intervention: From January 1, 2018, to June 5, 2024, 918 patients were assigned to the daily PCT-guided protocol, 924 to the daily CRP-guided protocol, and 918 assigned to standard care.
Main Outcomes and Measures: The primary outcomes were total duration of antibiotics (effectiveness) and all-cause mortality (safety) to 28 days. Secondary outcomes included critical care unit data and hospital stay data. Ninety-day all-cause mortality was also collected.
Results: Among the randomized patients (mean age 60.2 [SD, 15.4] years; 60.3% males), there was a significant reduction in antibiotic duration from randomization to 28 days for those in the daily PCT-guided protocol compared with standard care (mean duration, 10.7 [SD, 7.6] days for standard care and 9.8 [SD, 7.2] days for PCT; mean difference, 0.88 days; 95% CI, 0.19 to 1.58, P = .01). For all-cause mortality up to 28 days, the daily PCT-guided protocol was noninferior to standard care, where the noninferiority margin was set at 5.4% (19.4% [170 of 878] of patients receiving standard care; 20.9% [184 of 879], PCT; absolute difference, 1.57; 95% CI, −2.18 to 5.32; P = .02). No difference was found in antibiotic duration for standard care vs daily CRP-guided protocol (mean duration, 10.6 [7.7] days for CRP; mean difference, 0.09; 95% CI, −0.60 to 0.79; P = .79). For all-cause mortality, the daily CRP-guided protocol was inconclusive compared with standard care (21.1% [184 of 874] for CRP; absolute difference, 1.69; 95% CI, −2.07 to 5.45; P = .03).
Conclusions and Relevance: Care guided by measurement of PCT reduces antibiotic duration safely compared with standard care, but CRP does not. All-cause mortality for CRP was inconclusive.
Trial Registration: isrctn.org Identifier: ISRCTN4747324
Outlier detection in cardiac diffusion tensor imaging: Shot rejection or robust fitting?
Get PDFCardiac diffusion tensor imaging (cDTI) is highly prone to image corruption, yet robust-fitting methods are rarely used. Single voxel outlier detection (SVOD) can overlook corruptions that are visually obvious, perhaps causing reluctance to replace whole-image shot-rejection (SR) despite its own deficiencies. SVOD’s deficiencies may be relatively unimportant: corrupted signals that are not statistical outliers may not be detrimental. Multiple voxel outlier detection (MVOD), using a local myocardial neighbourhood, may overcome the shared deficiencies of SR and SVOD for cDTI while keeping the benefits of both. Here, robust fitting methods using M-estimators are derived for both non-linear least squares and weighted least squares fitting, and outlier detection is applied using (i) SVOD; and (ii) SVOD and MVOD. These methods, along with non-robust fitting with/without SR, are applied to cDTI datasets from healthy volunteers and hypertrophic cardiomyopathy patients. Robust fitting methods produce larger group differences with more statistical significance for MD, FA, and E2A, versus non-robust methods, with MVOD giving the largest group differences for MD and FA. Visual analysis demonstrates the superiority of robust-fitting methods over SR, especially when it is difficult to partition the images into good and bad sets. Synthetic experiments confirm that MVOD gives lower root-mean-square-error than SVOD
View-symmetric representations of faces in human and artificial neural networks
Get PDFView symmetry has been suggested to be an important intermediate representation between view-specific and view-invariant representations of faces in the human brain. Here, we compared view-symmetry in humans and a deep convolutional neural network (DCNN) trained to recognise faces. First, we compared the output of the DCNN to head rotations in yaw (left-right), pitch (up-down) and roll (in-plane rotation). For yaw, an initial view-specific representation was evident in the convolutional layers, but a view-symmetric representation emerged in the fully-connected layers. Consistent with a role in the recognition of faces, we found that view-symmetric responses to yaw were greater for same identity compared to different identity faces. In contrast, we did not find a similar transition from view-specific to view-symmetric representations in the DCNN for either pitch or roll. These findings suggest that view-symmetry emerges when opposite rotations of the head lead to mirror images. Next, we compared the view-symmetric patterns of response to yaw in the DCNN with corresponding behavioural and neural responses in humans. We found that responses in the fully-connected layers of the DCNN correlated with judgements of perceptual similarity and with the responses of higher visual regions. These findings suggest that view-symmetric representations may be computationally efficient way to represent faces in humans and artificial neural networks for the recognition of identity
A longitudinal investigation of the co-development and bidirectional relations among whole number arithmetic and conceptual and procedural fraction knowledge
Get PDFHow do conceptual and procedural fraction knowledge influence the development of each other over time? Is their pattern of development a reflection of instruction? In the present study we conducted a four-wave longitudinal investigation of the co- and bidirectional development of whole number arithmetic, and conceptual and procedural fraction knowledge during a critical phase of fraction learning. Chinese students (N = 1,055, Mage = 9.8, SD = 0.7) educated through a linear curriculum completed whole number arithmetic, and conceptual and procedural fraction assessments during the first and second terms in Grade 4 and Grade 5. Cross-lagged panel analysis, controlling for students’ non-verbal reasoning skills, revealed that conceptual and procedural fraction knowledge did not influence the development of one another prior to Grade 5. However, starting in Grade 5, a unidirectional pattern emerged, where conceptual fraction knowledge supported the development of procedural fraction knowledge. This unilateral conceptual-to-procedural pattern of development contrasts with findings from studies with students in the U.S., suggesting that educational experiences may shape the co-development of these two types of fraction knowledge. Furthermore, proficiency in whole number arithmetic predicted the development in both conceptual and procedural fraction knowledge, highlighting its important role alongside conceptual knowledge in supporting the acquisition of fraction procedures. Our findings emphasize the need to consider educational experiences and foster meaningful connections between concepts and procedures during fraction instruction while promoting mastery of whole number arithmetic to promote students’ development of fraction knowledge
Influence of electrode contact arrangements on Polarisation-Electric field measurements of ferroelectric ceramics: a case study of BaTiO3
Get PDFA range of partial top full bottom electrodes are used to explore the use of bi-polar Polarisation-Electric field (P–E) measurements to quantify recoverable energy (Wrec), energy loss (Wloss) and the efficiency (η) of ferroelectric BaTiO3 ceramics. The values obtained are dependent on the ratio of sample thickness (S) and top contact radius (r). With increasing S/r from 0.17 to 1.96 the P–E responses become increasingly distorted and broader. Measurements show Wrec increases by a factor of ∼ 1.4 but Wloss increases by a factor of ∼7 with η decreasing from ∼ 29% to 8%. Finite element modelling was used to simulate the experimental set-up of the sample/electrode arrangements using the Jiles-Atherton model to replicate the ferroelectric behaviour of BaTiO3. These models demonstrate the experimentally applied electric field using a simple geometric correction for sample thickness is an underestimation of the actual field experienced by the material under the top contact at high S/r values. We stress the importance of reporting the contact sizes and thicknesses of samples when using P–E measurements to assess Wrec, Wloss and η in non-linear dielectric materials. This will allow a fairer comparison of performances between various types of materials being considered for high-energy-density ceramic capacitors
Predicting fine‐scale distributions and emergent spatiotemporal patterns from temporally dynamic step selection simulations
Get PDFUnderstanding and predicting animal movement is fundamental to ecology and conservation management. Models that estimate and then predict animal movement and habitat selection parameters underpin diverse conservation applications, from mitigating invasive species spread to enhancing landscape connectivity. However, many predictive models overlook fine-scale temporal dynamics within their predictions, despite animals often displaying fine-scale behavioural variability that might significantly alter their movement, habitat selection and distribution over time. Incorporating fine-scale temporal dynamics, such as circadian rhythms, within predictive models might reduce the averaging out of such behaviours, thereby enhancing our ability to make predictions in both the short and long term. We tested whether the inclusion of fine-scale temporal dynamics improved both fine-scale (hourly) and long-term (seasonal) spatial predictions for a significant invasive species of northern Australia, the water buffalo Bubalus bubalis. Water buffalo require intensive management actions over vast, remote areas and display distinct circadian rhythms linked to habitat use. To inform management operations we generated hourly and dry season prediction maps by simulating trajectories from static and temporally dynamic step selection functions (SSFs) that were fitted to the GPS data of 13 water buffalo. We found that simulations generated from temporally dynamic models replicated the buffalo crepuscular movement patterns and dynamic habitat selection, resulting in more informative and accurate hourly predictions. Additionally, when the simulations were aggregated into long-term predictions, the dynamic models were more accurate and better able to highlight areas of concentrated habitat use that might indicate high-risk areas for environmental damage. Our findings emphasise the importance of incorporating fine-scale temporal dynamics in predictive models for species with clear dynamic behavioural patterns. By integrating temporally dynamic processes into animal movement trajectories, we demonstrate an approach that can enhance conservation management strategies and deepen our understanding of ecological and behavioural patterns across multiple timescales
Pickering polymerized high internal phase emulsions: fundamentals to advanced applications
Get PDFPickering-polymerized high internal phase emulsions have attracted attention since their successful first preparation 15 years ago, primarily due to their large pores and potential for functionalization during production. This review elucidates the fundamental principles of Pickering emulsions, Pickering HIPEs, and Pickering PolyHIPEs while comparing them to conventional surfactant-stabilized counterparts. The morphology of Pickering PolyHIPEs, with particular emphasis on methods for achieving interconnected structures, is explored and critically assessed. Lastly, the mechanical properties and diverse applications of these materials are reviewed, highlighting their use as catalytic supports and sorbent materials. The study aims to guide both new and experienced researchers in the field by comprehensively addressing the current potential and challenges of Pickering PolyHIPEs. Once the mystery behind the closed cellular pores of Pickering PolyHIPEs is resolved, these materials are expected to become more popular, particularly in applications where mass transfer is critical, such as tissue engineering
Volatile campaigns? The effects of shocks on campaign effectiveness in British general elections
Get PDFSome political events, such as the referendums on the UK’s continued membership of the EU in 2016, have the potential to alter substantially the electoral landscape, changing long-standing patterns of party alignment and support. Recent work suggests they also have the capacity to influence where and how much parties’ local campaign efforts might affect their support. Analysis of the fallout from the UK’s Brexit referendum suggests that after the vote, pro-Brexit parties’ campaigns yielded greater rewards the lower the local support for Brexit, while pro-Brexit parties’ campaigns became more effective where support for Brexit was higher. In this paper, we subject that claim to further scrutiny. Firstly, we employ alternative measures of campaign intensity with greater coverage of cases to assess whether the findings hold. Secondly, we broaden our understanding by looking at the campaigns of a wider range of parties than in the previous research. Thirdly, we extend the analysis to examine another political shock with major electoral consequences, the 2014 referendum on Scottish independence. Our results broadly confirm previous research findings, but we also uncover some important variations and differences. Parties do not campaign in a vacuum: no matter how professional their operations, the climate of national and local opinion affects their capacity to gain a hearing
Uncovering the impact of digital technologies on strategising: Evidence from a systematic literature review
Get PDFAdopting digital technologies in different organizations has become a trend over the last decade, yet our understanding regarding impact of digital technologies on strategising needs to be more cohersive. This paper reviews existing research on how digital transformation intersects with strategic management to adress this gap. Specifically, the aim is to explore how the digital context changes strategising. Based on a systematic review of empirical evidence from 163 journal papers, we showcased the manifestation of strategising in the digital age in terms of strategic practitioners, practices and praxis. By consolidating these findings, a typology of strategic actions in the digital age is developed and discussed, highlighting the interplay among changes in strategy-as-practice parameters. This framework clarifies in strategic scenarios of digital transformation and identifies various strategic directions and actions. Overall, we argue that although digital transformation has created additional strategic options, it has yet to change the underlying assumptions of strategising in firms
Specification, validation and verification of social, legal, ethical, empathetic and cultural requirements for autonomous agents
Get PDFAutonomous agents are increasingly being proposed for use in healthcare, assistive care, education, and other applications governed by complex human-centric norms. To ensure compliance with these norms, the rules they induce need to be unambiguously defined, checked for consistency, and used to verify the agent. In this paper, we introduce a framework for formal specification, validation and verification of social, legal, ethical, empathetic and cultural (SLEEC) rules for autonomous agents. Our framework comprises: (i) a language for specifying SLEEC rules and rule defeaters (that is, circumstances in which a rule does not apply or an alternative form of the rule is required); (ii) a formal semantics (defined in the process algebra tock-CSP) for the language; and (iii) methods for detecting conflicts and redundancy within a set of rules, and for verifying the compliance of an autonomous agent with such rules. We show the applicability of our framework for two autonomous agents from different domains: a firefighter UAV, and an assistive-dressing robot
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