Some clinical impressions of halothane

No Abstract

Chlorpromazine hydrochloride in anaesthesia

No Abstract

Rethinking ‘Advanced Search’: A New Approach to Complex Query Formulation

Knowledge workers such as patent agents, recruiters and media monitoring professionals undertake work tasks where search forms a core part of their duties. In these instances, the search task often involves the formulation of complex queries expressed as Boolean strings. However, creating effective Boolean queries remains an ongoing challenge, often compromised by errors and inefficiencies. In this demo paper, we present a new approach to query formulation in which concepts are expressed on a two-dimensional canvas and relationships are articulated using direct manipulation. This has the potential to eliminate many sources of error, makes the query semantics more transparent, and offers new opportunities for query refinement and optimisatio

An Open-Access Platform for Transparent and Reproducible Structured Searching

Knowledge workers such as patent agents, recruiters and legal researchers undertake work tasks in which search forms a core part of their duties. In these instances, the search task often involves formulation of complex queries expressed as Boolean strings. However, creating effective Boolean queries remains an ongoing challenge, often compromised by errors and inefficiencies. In this paper, we demonstrate a new approach to structured searching in which concepts are expressed as objects on a two-dimensional canvas. Interactive query suggestions are provided via an NLP services API, and support is offered for optimising, translating and sharing search strategies as executable artefacts. This eliminates many sources of error, makes the query semantics more transparent, and offers an open-access platform for sharing reproducible search strategies and best practices

Factors associated with acute kidney injury or failure in children undergoing cardiopulmonary bypass: a case‐controlled study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87176/1/j.1460-9592.2011.03532.x.pd

Some comments on "The Mathematical Universe"

I discuss some problems related to extreme mathematical realism, focusing on a recently proposed "shut-up-and-calculate" approach to physics (arXiv:0704.0646, arXiv:0709.4024). I offer arguments for a moderate alternative, the essence of which lies in the acceptance that mathematics is (at least in part) a human construction, and discuss concrete consequences of this--at first sight purely philosophical--difference in point of view.Comment: 11 page

Functional network dysconnectivity as a biomarker of treatment resistance in schizophrenia

Schizophrenia may develop from disruptions in functional connectivity regulated by neurotransmitters such as dopamine and acetylcholine. The modulatory effects of these neurotransmitters might explain how antipsychotics attenuate symptoms of schizophrenia and account for the variable response to antipsychotics observed in clinical practice. Based on the putative mechanisms of antipsychotics and evidence of disrupted connectivity in schizophrenia, we hypothesised that functional network connectivity, as assessed using network-based statistics, would exhibit differences between treatment response subtypes of schizophrenia and healthy controls. Resting-state functional MRI data were obtained from 17 healthy controls as well as individuals with schizophrenia who responded well to first-line atypical antipsychotics (first-line responders; FLR, n=18), had failed at least two trials of antipsychotics but responded to clozapine (treatment-resistant schizophrenia; TRS, n=18), or failed at least two trials of antipsychotics and a trial of clozapine (ultra-treatment-resistant schizophrenia; UTRS, n=16). Data were pre-processed using the Advanced Normalisation Toolkit and BrainWavelet Toolbox. Network connectivity was assessed using the Network-Based Statistics toolbox in Matlab. ANOVA revealed a significant difference in functional connectivity between groups that extended between cerebellar and parietal regions to the frontal cortex (p<0.05). Post-hoc T-tests revealed weaker network connectivity in individuals with UTRS compared with healthy controls but no other differences between groups. Results demonstrated distinct differences in functional connectivity between individuals with UTRS and healthy controls. Future work must determine whether these changes occur prior to the onset of treatment and if they can be used to predict resistance to antipsychotics during first-episode psychosis.This work was supported by The University of Auckland Faculty Research and Development Fund Project number 3624739, with support from the New Zealand Pharmacy Education and Research Fund Grant number 263, the New Zealand Schizophrenia Research Group Donation and the Oakley Mental Health Research Foundation. Carolyn McNabb was supported by a Vernon Tews Education Trust scholarship. Meghan McIlwain was supported by a University of Auckland Doctoral Scholarship and a New Zealand Federation of Graduate Women Fellowship. Valerie Anderson was supported by an Edith C. Coan Research Fellowship from The Auckland Medical Research Foundation

Observational longitudinal cohort study to determine progression to heart failure in a screened community population : the Echocardiographic Heart of England Screening Extension (ECHOES-X) study

OBJECTIVES: Rescreen a large community cohort to examine the progression to heart failure over time and the role of natriuretic peptide testing in screening. DESIGN: Observational longitudinal cohort study. SETTING: 16 socioeconomically diverse practices in central England. PARTICIPANTS: Participants from the original Echocardiographic Heart of England Screening (ECHOES) study were invited to attend for rescreening. OUTCOME MEASURES: Prevalence of heart failure at rescreening overall and for each original ECHOES subgroup. Test performance of N Terminal pro-B-type Natriuretic Peptide (NT-proBNP) levels at different thresholds for screening. RESULTS: 1618 of 3408 participants underwent screening which represented 47% of survivors and 26% of the original ECHOES cohort. A total of 176 (11%, 95% CI 9.4% to 12.5%) participants were classified as having heart failure at rescreening; 103 had heart failure with reduced ejection fraction (HFREF) and 73 had heart failure with preserved ejection fraction (HFPEF). Sixty-eight out of 1232 (5.5%, 95% CI 4.3% to 6.9%) participants who were recruited from the general population over the age of 45 and did not have heart failure in the original study, had heart failure on rescreening. An NT-proBNP cut-off of 400 pg/mL had sensitivity for a diagnosis of heart failure of 79.5% (95% CI 72.4% to 85.5%) and specificity of 87% (95% CI 85.1% to 88.8%). CONCLUSIONS: Rescreening identified new cases of HFREF and HFPEF. Progression to heart failure poses a significant threat over time. The natriuretic peptide cut-off level for ruling out heart failure must be low enough to ensure cases are not missed at screening

Functional network dysconnectivity as a biomarker of treatment resistance in schizophrenia.

Schizophrenia may develop from disruptions in functional connectivity regulated by neurotransmitters such as dopamine and acetylcholine. The modulatory effects of these neurotransmitters might explain how antipsychotics attenuate symptoms of schizophrenia and account for the variable response to antipsychotics observed in clinical practice. Based on the putative mechanisms of antipsychotics and evidence of disrupted connectivity in schizophrenia, we hypothesised that functional network connectivity, as assessed using network-based statistics, would exhibit differences between treatment response subtypes of schizophrenia and healthy controls. Resting-state functional MRI data were obtained from 17 healthy controls as well as individuals with schizophrenia who responded well to first-line atypical antipsychotics (first-line responders; FLR, n=18), had failed at least two trials of antipsychotics but responded to clozapine (treatment-resistant schizophrenia; TRS, n=18), or failed at least two trials of antipsychotics and a trial of clozapine (ultra-treatment-resistant schizophrenia; UTRS, n=16). Data were pre-processed using the Advanced Normalization Toolkit and BrainWavelet Toolbox. Network connectivity was assessed using the Network-Based Statistics toolbox in Matlab. ANOVA revealed a significant difference in functional connectivity between groups that extended between cerebellar and parietal regions to the frontal cortex (p<0.05). Post-hoc t-tests revealed weaker network connectivity in individuals with UTRS compared with healthy controls but no other differences between groups. Results demonstrated distinct differences in functional connectivity between individuals with UTRS and healthy controls. Future work must determine whether these changes occur prior to the onset of treatment and if they can be used to predict resistance to antipsychotics during first-episode psychosis

Ultra scale-down approaches to study the centrifugal harvest for viral vaccine production

Large scale continuous cell‐line cultures promise greater reproducibility and efficacy for the production of influenza vaccines, and adenovirus for gene therapy. This paper seeks to use an existing validated ultra scale‐down tool, which is designed to mimic the commercial scale process environment using only milliliters of material, to provide some initial insight into the performance of the harvest step for these processes. The performance of industrial scale centrifugation and subsequent downstream process units is significantly affected by shear. The properties of these cells, in particular their shear sensitivity, may be changed considerably by production of a viral product, but literature on this is limited to date. In addition, the scale‐down tool used here has not previously been applied to the clarification of virus production processes. The results indicate that virus infected cells do not actually show any increase in sensitivity to shear, and may indeed become less shear sensitive, in a similar manner to that previously observed in old or dead cell cultures. Clarification may be most significantly dependent on the virus release mechanism, with the budding influenza virus producing a much greater decrease in clarification than the lytic, non‐enveloped adenovirus. A good match was also demonstrated to the industrial scale performance in terms of clarification, protein release, and impurity profile.UK Engineering and Physical Sciences Research Council, EPSRC. Grant Number: EP/G034656/1Published versio