3,433 research outputs found
Evidence-Based Perioperative Medicine comes of age: the Perioperative Quality Initiative (POQI): The 1st Consensus Conference of the Perioperative Quality Initiative (POQI).
The 1st POQI Consensus Conference occurred in Durham, NC, on March 4-5, 2016, and was supported by the American Society of Enhanced Recovery (ASER) and Evidence-Based Perioperative Medicine (EBPOM). The conference focused on enhanced recovery for colorectal surgery and discussed four topics-perioperative analgesia, perioperative fluid management, preventing nosocomial infection, and measurement and quality in enhanced recovery pathways
Maze solvers demystified and some other thoughts
There is a growing interest towards implementation of maze solving in
spatially-extended physical, chemical and living systems. Several reports of
prototypes attracted great publicity, e.g. maze solving with slime mould and
epithelial cells, maze navigating droplets. We show that most prototypes
utilise one of two phenomena: a shortest path in a maze is a path of the least
resistance for fluid and current flow, and a shortest path is a path of the
steepest gradient of chemoattractants. We discuss that substrates with
so-called maze-solving capabilities simply trace flow currents or chemical
diffusion gradients. We illustrate our thoughts with a model of flow and
experiments with slime mould. The chapter ends with a discussion of experiments
on maze solving with plant roots and leeches which show limitations of the
chemical diffusion maze-solving approach.Comment: This is a preliminary version of the chapter to be published in
Adamatzky A. (Ed.) Shortest path solvers. From software to wetware. Springer,
201
Erratum to: Impact of intravenous fluid composition on outcomes in patients with systemic inflammatory response syndrome Critical Care (2016) 20:17 DOI 10.1186/s13054-016-1187-7
Associations between perioperative fluid management and patient outcomes: a multicentre retrospective study
BACKGROUND: Postoperative complications increase hospital length of stay and patient mortality. Optimal perioperative fluid management should decrease patient complications. This study examined associations between fluid volume and noncardiac surgery patient outcomes within a large multicentre US surgical cohort. METHODS: Adults undergoing noncardiac procedures from January 1, 2012 to December 31, 2017, with a postoperative length of stay ≥24 h, were extracted from a large US electronic health record database. Patients were segmented into quintiles based on recorded perioperative fluid volumes with Quintile 3 (Q3) serving as the reference. The primary outcome was defined as a composite of any complications during the surgical admission and a postoperative length of stay ≥7 days. Secondary outcomes included in-hospital mortality, respiratory complications, and acute kidney injury. RESULTS: A total of 35 736 patients met the study criteria. There was a U-shaped pattern with highest (Q5) and lowest (Q1) quintiles of fluid volumes having increased odds of complications and a postoperative length of stay ≥7 days (Q5: odds ratio [OR] 1.51 [95% confidence interval {CI}: 1.30-1.74], P<0.001; Q1: OR 1.20 [95% CI: 1.04-1.38], P=0.011) compared with Q3. Patients in Q5 had greater odds of more severe acute kidney injury compared with Q3 (OR 1.52 [95% CI: 1.22-1.90]; P<0.001) and respiratory complications (OR 1.44 [95% CI: 1.17-1.77]; P<0.001). CONCLUSIONS: Both very high and very low perioperative fluid volumes were associated with an increase in complications after noncardiac surgery
Oscillatory, Computational, and Behavioral Evidence for Impaired GABAergic Inhibition in Schizophrenia
The dysconnection hypothesis of schizophrenia (SZ) proposes that psychosis is best understood in terms of aberrant connectivity. Specifically, it suggests that dysconnectivity arises through aberrant synaptic modulation associated with deficits in GABAergic inhibition, excitation-inhibition balance and disturbances of high-frequency oscillations. Using a computational model combined with a graded-difficulty visual orientation discrimination paradigm, we demonstrate that, in SZ, perceptual performance is determined by the balance of excitation-inhibition in superficial cortical layers. Twenty-eight individuals with a DSM-IV diagnosis of SZ, and 30 age- and gender-matched healthy controls participated in a psychophysics orientation discrimination task, a visual grating magnetoencephalography (MEG) recording, and a magnetic resonance spectroscopy (MRS) scan for GABA. Using a neurophysiologically informed model, we quantified group differences in GABA, gamma measures, and the predictive validity of model parameters for orientation discrimination in the SZ group. MEG visual gamma frequency was reduced in SZ, with lower peak frequency associated with more severe negative symptoms. Orientation discrimination performance was impaired in SZ. Dynamic causal modeling of the MEG data showed that local synaptic connections were reduced in SZ and local inhibition correlated negatively with the severity of negative symptoms. The effective connectivity between inhibitory interneurons and superficial pyramidal cells predicted orientation discrimination performance within the SZ group; consistent with graded, behaviorally relevant, disease-related changes in local GABAergic connections. Occipital GABA levels were significantly reduced in SZ but did not predict behavioral performance or oscillatory measures. These findings endorse the importance, and behavioral relevance, of GABAergic synaptic disconnection in schizophrenia that underwrites excitation-inhibition balance
Using fractional exhaled nitric oxide (FeNO) to diagnose steroid-responsive disease and guide asthma management in routine care
Acknowledgements We thank Robin Taylor for his informative thinking and publications on FeNO, which have helped to influence and direct the thinking of the authors. Funding Extraction of the real-life dataset was funded by Research in Real Life Limited, the analysis of the dataset and the writing of this manuscript were co-funded (50:50) by Research in Real Life Limited and Aerocrine.Peer reviewedPublisher PD
Modulation of long-term potentiation following microdoses of LSD captured by thalamo-cortical modelling in a randomised, controlled trial
This is the final version. Available from BMC via the DOI in this record. Data availability:
The datasets used and/or analysed during the current study are available from
the corresponding author on reasonable request. Code for the TCM model is
available here: https://github.com/alexandershaw4/LTP_code.Background Microdosing psychedelics is a phenomenon with claimed cognitive benefts that are relatively untested
clinically. Pre-clinically, psychedelics have demonstrated enhancing efects on neuroplasticity, which cannot be measured directly in humans, but may be indexed by non-invasive electroencephalography (EEG) paradigms. This study
used a visual long-term potentiation (LTP) EEG paradigm to test the efects of microdosed lysergic acid diethylamide
(LSD) on neural plasticity, both acutely while on the drug and cumulatively after microdosing every third day for six
weeks. Healthy adult males (n=80) completed the visual LTP paradigm at baseline, 2.5 h following a dose of 10 µg
of LSD or inactive placebo, and 6 weeks later after taking 14 repeated microdoses. Visually induced LTP was used
as indirect index of neural plasticity. Surface level event-related potential (ERPs) based analyses are presented alongside dynamic causal modelling of the source localised data using a generative thalamocortical model (TCM) of visual
cortex to elucidate underlying synaptic circuitry.
Results Event-related potential (ERP) analyses of N1b and P2 components did not show evidence of changes
in visually induced LTP by LSD either acutely or after 6 weeks of regular dosing. However modelling the complete
timecourse of the ERP with the TCM demonstrated changes in laminar connectivity in primary visual cortex. This
primarily included changes to self-gain and inhibitory input parameters acutely. Layer 2/3 to layer 5 excitatory connectivity was also diferent between LSD and placebo groups. After regular dosing only excitatory input from layer 2/3
into layer 5 and inhibitory input into layer 4 were diferent between groups.
Conclusions Without modulation of the ERPs it is difcult to relate the fndings to other studies visually inducing LTP.
It also indicates the classic peak analysis may not be sensitive enough to demonstrate evidence for changes in LTP
plasticity in humans at such low doses. The TCM provides a more sensitive approach to assessing changes to plasticity
as diferences in plasticity mediated laminar connectivity were found between the LSD and placebo groups.Health Research Council of New ZealandMindBio Therapeutics Ltd
Neurophysiological evidence that frontoparietal connectivity and GABA-A receptor changes underpin the antidepressant response to ketamine
This is the final version. Available on open access from Springer nature via the DOI in this recordData availability: The data underlying this article cannot be shared publicly as it was not part of the original ethics application to do so. The data will be shared on reasonable request to the corresponding author.Revealing the acute cortical pharmacodynamics of an antidepressant dose of ketamine in humans with depression is key to determining the specific mechanism(s) of action for alleviating symptoms. While the downstream effects are characterised by increases in plasticity and reductions in depressive symptoms—it is the acute response in the brain that triggers this cascade of events. Computational modelling of cortical interlaminar and cortico-cortical connectivity and receptor dynamics provide the opportunity to interrogate this question using human electroencephalography (EEG) data recorded during a ketamine infusion. Here, resting-state EEG was recorded in a group of 30 patients with major depressive disorder (MDD) at baseline and during a 0.44 mg/kg ketamine dose comprising a bolus and infusion. Fronto-parietal connectivity was assessed using dynamic causal modelling to fit a thalamocortical model to hierarchically connected nodes in the medial prefrontal cortex and superior parietal lobule. We found a significant increase in parietal-to-frontal AMPA-mediated connectivity and a significant decrease in the frontal GABA time constant. Both parameter changes were correlated across participants with the antidepressant response to ketamine. Changes to the NMDA receptor time constant and inhibitory intraneuronal input into superficial pyramidal cells did not survive correction for multiple comparisons and were not correlated with the antidepressant response. These results provide evidence that the antidepressant effects of ketamine may be mediated by acute fronto-parietal connectivity and GABA receptor dynamics. Furthermore, it supports the large body of literature suggesting the acute mechanism underlying ketamine’s antidepressant properties is related to GABA-A and AMPA receptors rather than NMDA receptor antagonism.Health Research Council of New ZealandWellcome Trus
Undergraduate medical textbooks do not provide adequate information on intravenous fluid therapy: a systematic survey and suggestions for improvement
<b>Background</b><p></p>
Inappropriate prescribing of intravenous (IV) fluid, particularly 0.9% sodium chloride, causes post-operative complications. Fluid prescription is often left to junior medical staff and is frequently poorly managed. One reason for poor intravenous fluid prescribing practices could be inadequate coverage of this topic in the textbooks that are used.<p></p>
<b>Methods</b><p></p>
We formulated a comprehensive set of topics, related to important common clinical situations involving IV fluid therapy, (routine fluid replacement, fluid loss, fluids overload) to assess the adequacy of textbooks in common use. We assessed 29 medical textbooks widely available to students in the UK, scoring the presence of information provided by each book on each of the topics. The scores indicated how fully the topics were considered: not at all, partly, and adequately. No attempt was made to judge the quality of the information, because there is no consensus on these topics.<p></p>
<b>Results</b><p></p>
The maximum score that a book could achieve was 52. Three of the topics we chose were not considered by any of the books. Discounting these topics as “too esoteric”, the maximum possible score became 46. One textbook gained a score of 45, but the general score was poor (median 11, quartiles 4, 21). In particular, coverage of routine postoperative management was inadequate.<p></p>
<b>Conclusions</b><p></p>
Textbooks for undergraduates cover the topic of intravenous therapy badly, which may partly explain the poor knowledge and performance of junior doctors in this important field. Systematic revision of current textbooks might improve knowledge and practice by junior doctors. Careful definition of the remit and content of textbooks should be applied more widely to ensure quality and “fitness for purpose”, and avoid omission of vital knowledge
Influence of a knot on the strength of a polymer strand
Many experiments have been done to determine the relative strength of
different knots, and these show that the break in a knotted rope almost
invariably occurs at a point just outside the `entrance' to the knot. The
influence of knots on the properties of polymers has become of great interest,
in part because of their effect on mechanical properties. Knot theory applied
to the topology of macromolecules indicates that the simple trefoil or
`overhand' knot is likely to be present with high probability in any long
polymer strand. Fragments of DNA have been observed to contain such knots in
experiments and computer simulations. Here we use {\it ab initio} computational
methods to investigate the effect of a trefoil knot on the breaking strength of
a polymer strand. We find that the knot weakens the strand significantly, and
that, like a knotted rope, it breaks under tension at the entrance to the knot.Comment: 3 pages, 4 figure
- …