Time, action and psychosis: using subjective time to investigate the effects of ketamine on sense of agency

Sense of agency refers to the experience of initiating and controlling actions in order to influence events in the outside world. A disturbed sense of agency is found in certain psychiatric and neurological disorders, most notably schizophrenia. Sense of agency is associated with a subjective compression of time: actions and their outcomes are perceived as bound together in time. This is known as ‘intentional binding’ and, in healthy adults, depends partly on advance prediction of action outcomes. Notably, this predictive contribution is disrupted in patients with schizophrenia. In the present study we aimed to characterise the psychotomimetic effect of ketamine, a drug model for psychosis, on the predictive contribution to intentional binding. It was shown that ketamine produced a disruption that closely resembled previous data from patients in the early, prodromal, stage of schizophrenic illness. These results are discussed in terms of established models of delusion formation in schizophrenia. The link between time and agency, more generally, is also considered

Drug administration errors by South African anaesthetists - a survey

Objectives. To investigate the incidence, nature of and factors contributing towards wrong drug administrations by South African anaesthetists. Design. A confidential, self-reporting survey was sent out to the 720 anaesthetists on the database of the South African Society of Anaesthesiologists. Results. A total of 133 questionnaires were returned for analysis (18.5% response rate). Of the respondents, 125 (94%) admitted to having inadvertently administered a wrong drug. Thirty respondents (22.6%) said they had made errors on at least four occasions. A total of 303 specific wrong drug administrations were described. Nearly 50% involved muscle relaxants. A further 43 incidents (14%) involved the erroneous administration of vasoactive drugs. Five deaths and 3 nonfatal cardiac arrests were reported. In 9.9% of incidents the anaesthetic time was prolonged by more than 30 minutes. Contributory causes identified included syringe swaps (40%), misidentification of drugs (27.1%), fatigue (14.1%), distractions (4.7%), and mislabelling of syringes (4.7%). Only 19% of respondents regularly use colour-coded syringe labels complying with the national standard. Conclusions. Most anaesthetists experienced at least one drug error. The incidence of wrong drug administrations by South African anaesthetists appears to be similar to that in Australasia and Canada. The commonest error was a ‘syringe swap' involving muscle relaxants. Most drug errors are inconsequential. An important minority of incidents result in severe morbidity or death. The study supports efforts to improve ampoule labelling, to encourage the use of syringe labels based on the international colour code and to develop a national reporting system for such incidents. South African Medical Journal Vol. 96(7) 2006: 630-63

Drug administration errors by South African anaesthetists – a survey

No Abstract. Southern African Journal of Anaesthesia and Analgesia Vol. 12(1) 2006: 4

Intrinsic Cornu Ammonis Area 1 Theta-Nested Gamma Oscillations Induced by Optogenetic Theta Frequency Stimulation.

UNLABELLED: Gamma oscillations (30-120 Hz) are thought to be important for various cognitive functions, including perception and working memory, and disruption of these oscillations has been implicated in brain disorders, such as schizophrenia and Alzheimer's disease. The cornu ammonis area 1 (CA1) of the hippocampus receives gamma frequency inputs from upstream regions (cornu ammonis area 3 and medial entorhinal cortex) and generates itself a faster gamma oscillation. The exact nature and origin of the intrinsic CA1 gamma oscillation is still under debate. Here, we expressed channel rhodopsin-2 under the CaMKIIα promoter in mice and prepared hippocampal slices to produce a model of intrinsic CA1 gamma oscillations. Sinusoidal optical stimulation of CA1 at theta frequency was found to induce robust theta-nested gamma oscillations with a temporal and spatial profile similar to CA1 gamma in vivo The results suggest the presence of a single gamma rhythm generator with a frequency range of 65-75 Hz at 32 °C. Pharmacological analysis found that the oscillations depended on both AMPA and GABAA receptors. Cell-attached and whole-cell recordings revealed that excitatory neuron firing slightly preceded interneuron firing within each gamma cycle, suggesting that this intrinsic CA1 gamma oscillation is generated with a pyramidal-interneuron circuit mechanism. SIGNIFICANCE STATEMENT: This study demonstrates that the cornu ammonis area 1 (CA1) is capable of generating intrinsic gamma oscillations in response to theta input. This gamma generator is independent of activity in the upstream regions, highlighting that CA1 can produce its own gamma oscillation in addition to inheriting activity from the upstream regions. This supports the theory that gamma oscillations predominantly function to achieve local synchrony, and that a local gamma generated in each area conducts the signal to the downstream region.J.L.B. is support by a Biotechnology and Biological Sciences Research Council CASE Studentship in collaboration with Eli Lilly and Company, and P.R.F.M. is supported by a CAPES Science without Borders Cambridge Scholarship.This is the final version of the article. It first appeared from the Society for Neuroscience via http://dx.doi.org/10.1523/JNEUROSCI.3150-15.201

Julian of Norwich and her children today: Editions, translations and versions of her revelations

The viability of such concepts as "authorial intention," "the original text," "critical edition" and, above all, "scholarly editorial objectivity" is not what it was, and a study of the textual progeny of the revelations of Julian of Norwich--editions, versions, translations and selections--does little to rehabilitate them. Rather it tends to support the view that a history of reading is indeed a history of misreading or, more positively, that texts can have an organic life of their own that allows them to reproduce and evolve quite independently of their author. Julian's texts have had a more robustly continuous life than those of any other Middle English mystic. Their history--in manuscript and print, in editions more or less approximating Middle English and in translations more or less approaching Modern English--is virtually unbroken since the fifteenth century. But on this perilous journey, many and strange are the clutches into which she and her textual progeny have fallen

A comparison of collision cross section values obtained via travelling wave ion mobility-mass spectrometry and ultra high performance liquid chromatography-ion mobility-mass spectrometry : application to the characterisation of metabolites in rat urine

A comprehensive Collision Cross Section (CCS) library was obtained via Travelling Wave Ion Guide mobility measurements through direct infusion (DI). The library consists of CCS and Mass Spectral (MS) data in negative and positive ElectroSpray Ionisation (ESI) mode for 463 and 479 endogenous metabolites, respectively. For both ionisation modes combined, TWCCSN2 data were obtained for 542 non-redundant metabolites. These data were acquired on two different ion mobility enabled orthogonal acceleration QToF MS systems in two different laboratories, with the majority of the resulting TWCCSN2 values (from detected compounds) found to be within 1% of one another. Validation of these results against two independent, external TWCCSN2 data sources and predicted TWCCSN2 values indicated to be within 1-2% of these other values. The same metabolites were then analysed using a rapid reversed-phase ultra (high) performance liquid chromatographic (U(H)PLC) separation combined with IM and MS (IM-MS) thus providing retention time (tr), m/z and TWCCSN2 values (with the latter compared with the DI-IM-MS data). Analytes for which TWCCSN2 values were obtained by U(H)PLC-IM-MS showed good agreement with the results obtained from DI-IM-MS. The repeatability of the TWCCSN2 values obtained for these metabolites on the different ion mobility QToF systems, using either DI or LC, encouraged the further evaluation of the U(H)PLC-IM-MS approach via the analysis of samples of rat urine, from control and methotrexate-treated animals, in order to assess the potential of the approach for metabolite identification and profiling in metabolic phenotyping studies. Based on the database derived from the standards 63 metabolites were identified in rat urine, using positive ESI, based on the combination of tr, TWCCSN2 and MS data.</p

Community-based palliative care is associated with reduced emergency department use by people with dementia in their last year of life: A retrospective cohort study

Objective: To describe patterns in the use of hospital emergency departments in the last year of life by people who died with dementia and whether this was modified by use of community-based palliative care. Design: Retrospective population-based cohort study of people in their last year of life. Time-to-event analyses were performed using cumulative hazard functions and flexible parametric proportional hazards regression models. Setting/participants: All people living in Western Australia who died with dementia in the 2-year period 1 January 2009 to 31 December 2010 (dementia cohort; N = 5261). A comparative cohort of decedents without dementia who died from other conditions amenable to palliative care (N = 2685). Results: More than 70% of both the dementia and comparative cohorts attended hospital emergency departments in the last year of life. Only 6% of the dementia cohort used community-based palliative care compared to 26% of the comparative cohort. Decedents with dementia who were not receiving community-based palliative care attended hospital emergency departments more frequently than people receiving community-based palliative care. The magnitude of the increased rate of emergency department visits varied over the last year of life from 1.4 (95% confidence interval: 1.1–1.9) times more often in the first 3 months of follow-up to 6.7 (95% confidence interval: 4.7–9.6) times more frequently in the weeks immediately preceding death. Conclusions: Community-based palliative care of people who die with or of dementia is relatively infrequent but associated with significant reductions in hospital emergency department use in the last year of life

A universal two-way approach for estimating unknown frequencies for unknown number of sinusoids in a signal based on eigenspace analysis of Hankel matrix

YesWe develop a novel approach to estimate the n unknown constituent frequencies of a noiseless signal that comprises of unknown number, n, of sinusoids of unknown phases and unknown amplitudes. The new two way approach uses two constraints to accurately estimate the unknown frequencies of the sinusoidal components in a signal. The new approach serves as a verification test for the estimated unknown frequencies through the estimated count of the unknown number of frequencies. The Hankel matrix, of the time domain samples of the signal, is used as a basis for further analysis in the Pisarenko harmonic decomposition. The new constraints, the Existence Factor (EF) and the Component Factor (CF), have been introduced in the methodology based on the relationships between the components of the sinusoidal signal and the eigenspace of the Hankel matrix. The performance of the developed approach has been tested to correctly estimate any number of frequencies within a signal with or without a fixed unknown bias. The method has also been tested to accurately estimate the very closely spaced low frequencies.Innovate U