Modelling the spatial effects of the anaesthetic-induced phase-transition in the cerebral cortex

In this thesis I investigate the theoretical stochastic behaviour of a one-dimensional model of the cerebral cortex, exposed to varying concentrations of a general anaesthetic agent. The model is that of Steyn-Ross et al. (2003). Theirs is a continuum theory based on the electrical response of a neural mass known as the macrocolum. The model predicts that as anaethetic concentration is increased the cortex will undergo a sudden electrical phase transition corresponding to loss of consciousness (LOC). Similarly, at return of consciousness (ROC) a second distinct phase transition is predicted. Spatial variability is incorporated into the original homogeneous cortical model of Steyn-Ross et al. (1999). This is done by including the possibility of spatial variation in distant excitatory and inhibitory inputs. By modelling the cortex in this way, we hope to gain an understanding of how the cortex functions, and how anaethestic agents “shut-down” the brain. I simulate the one-dimensional system numerically in order to verify analytical predictions. Both analytical and numerical results show an increase in the coherence (spatial-correlation) of the electrical activity along the one-dimensional rod on approach to both LOC and ROC. Theory and simulations also show that the electrical fluctuations in the unconscious cortex should have a larger correlation length than for the cortex in the conscious state, suggesting that the unconscious state is the more ordered. I derive the theoretical power spectrum and discuss some of its properties. By expanding the model to include spatial variability, we discover the possibility of self-organized structures forming spontaneously in the one-dimensional cortex. These “Turing” or dissipative structures are stationary in time, showing giant DC voltage variations along the cortical rod. Although the dissipative structures can from a rich variety of pseudo-periodic patterns, the physiological significance of such stationary neural structures is not yet clear

Why Dream

Photograph of Henry Wadsworth; Illustration of jazz ensemble with various objectshttps://scholarsjunction.msstate.edu/cht-sheet-music/6788/thumbnail.jp

Spontaneous and stimulated emission tuning characteristics of a Josephson junction in a microcavity

We have investigated theoretically the tuning characteristics of a Josephson junction within a microcavity for one-photon spontaneous emission and for one-photon and two-photon stimulated emission. For spontaneous emission, we have established the linear relationship between the magnetic induction and the voltage needed to tune the system to emit at resonant frequencies. For stimulated emission, we have found an oscillatory dependence of the emission rate on the initial Cooper pair phase difference and the phase of the applied field. Under specific conditions, we have also calculated the values of the applied radiation amplitude for the first few emission maxima of the system and for the first five junction-cavity resonances for each process. Since the emission of photons can be controlled, it may be possible to use such a system to produce photons on demand. Such sources will have applications in the fields of quantum cryptography, communications and computation

Antlia Dwarf Galaxy: Distance, quantitative morphology and recent formation history via statistical field correction

We apply a statistical field correction technique originally designed to determine membership of high redshift galaxy clusters to Hubble Space Telescope imaging of the Antlia Dwarf Galaxy; a galaxy at the very edge of the Local Group. Using the tip of the red giant branch standard candle method coupled with a simple Sobel edge detection filter we find a new distance to Antlia of 1.31 +/- 0.03 Mpc. For the first time for a Local Group Member, we compute the concentration, asymmetry and clumpiness (CAS) quantitative morphology parameters for Antlia from the distribution of resolved stars in the HST/ACS field, corrected with a new method for contaminants and complement these parameters with the Gini coefficient (G) and the second order moment of the brightest 20 per cent of the flux (M_20). We show that it is a classic dwarf elliptical (C = 2.0, A = 0.063, S = 0.077, G = 0.39 and M_20 = -1.17 in the F814W band), but has an appreciable blue stellar population at its core, confirming on-going star-formation. The values of asymmetry and clumpiness, as well as Gini and M_20 are consistent with an undisturbed galaxy. Although our analysis suggests that Antlia may not be tidally influenced by NGC 3109 it does not necessarily preclude such interaction.Comment: Accepted for publication in MNRA

Lateralization of infant holding by mothers: a longitudinal evaluation of variations over the first 12 weeks

The maternal preference to hold infants on the left rather than right side of the body was examined longitudinally, with attention to four explanations: maternal monitoring of infant state, maternal handedness, infant proximity to the mother’s heartbeat, and preferred infant head position. The side and site of holding were measured over the first twelve weeks of the lives of 24 infants. Information about group and individual consistency in holding side allowed novel evaluation of the theories. A strong bias to hold on the left dropped below significance when the infants were aged twelve weeks and was limited to specific holding positions. Findings were generally consistent with the monitoring hypothesis, and little support was found for the three alternative explanations

Inside the whale: the structure and dynamics of the isolated Cetus dwarf spheroidal

This paper presents a study of the Cetus dwarf, an isolated dwarf galaxy within the Local Group. A matched-filter analysis of the INT/WFC imaging of this system reveals no evidence for significant tidal debris that could have been torn from the galaxy, bolstering the hypothesis that Cetus has never significantly interacted with either the Milky Way or M31. Additionally, Keck/Deimos spectroscopic observations identify this galaxy as a distinct kinematic population possessing a systematic velocity of $-87\pm2{\rm km\ s^{-1}}$and with a velocity dispersion of$17\pm2{\rm km s^{-1}}$; while tentative, these data also suggest that Cetus possesses a moderate rotational velocity of$\sim8{\rm km s^{-1}}$. The population is confirmed to be relatively metal-poor, consistent with${\rm [Fe/H]\sim-1.9}$, and, assuming virial equilibrium, implies that the Cetus dwarf galaxy possesses a$M/L\sim70$. It appears, therefore, that Cetus may represent a primordial dwarf galaxy, retaining the kinematic and structural properties lost by other members of the dwarf population of the Local Group in their interactions with the large galaxies. An analysis of Cetus's orbit through the Local Group indicates that it is at apocentre; taken in conjunction with the general dwarf population, this shows the mass of the Local Group to be$\gta2\times10^{12}M_\odot$.Comment: Accepted for publication in MNRA

Comparison of microbiological diagnosis of urinary tract infection in young children by routine health service laboratories and a research laboratory: Diagnostic cohort study

OBJECTIVES: To compare the validity of diagnosis of urinary tract infection (UTI) through urine culture between samples processed in routine health service laboratories and those processed in a research laboratory. POPULATION AND METHODS: We conducted a prospective diagnostic cohort study in 4808 acutely ill children aged <5 years attending UK primary health care. UTI, defined as pure/predominant growth ≥105 CFU/mL of a uropathogen (the reference standard), was diagnosed at routine health service laboratories and a central research laboratory by culture of urine samples. We calculated areas under the receiver-operator curve (AUC) for UTI predicted by pre-specified symptoms, signs and dipstick test results (the "index test"), separately according to whether samples were obtained by clean catch or nappy (diaper) pads. RESULTS: 251 (5.2%) and 88 (1.8%) children were classified as UTI positive by health service and research laboratories respectively. Agreement between laboratories was moderate (kappa = 0.36; 95% confidence interval [CI] 0.29, 0.43), and better for clean catch (0.54; 0.45, 0.63) than nappy pad samples (0.20; 0.12, 0.28). In clean catch samples, the AUC was lower for health service laboratories (AUC = 0.75; 95% CI 0.69, 0.80) than the research laboratory (0.86; 0.79, 0.92). Values of AUC were lower in nappy pad samples (0.65 [0.61, 0.70] and 0.79 [0.70, 0.88] for health service and research laboratory positivity, respectively) than clean catch samples. CONCLUSIONS: The agreement of microbiological diagnosis of UTI comparing routine health service laboratories with a research laboratory was moderate for clean catch samples and poor for nappy pad samples and reliability is lower for nappy pad than for clean catch samples. Positive results from the research laboratory appear more likely to reflect real UTIs than those from routine health service laboratories, many of which (particularly from nappy pad samples) could be due to contamination. Health service laboratories should consider adopting procedures used in the research laboratory for paediatric urine samples. Primary care clinicians should try to obtain clean catch samples, even in very young children

What carcinoembryonic antigen level should trigger further investigation during colorectal cancer follow-up? A systematic review and secondary analysis of a randomised controlled trial

Background Following primary surgical and adjuvant treatment for colorectal cancer, many patients are routinely followed up with blood carcinoembryonic antigen (CEA) testing. Objective To determine how the CEA test result should be interpreted to inform the decision to undertake further investigation to detect treatable recurrences. Design Two studies were conducted: (1) a Cochrane review of existing studies describing the diagnostic accuracy of blood CEA testing for detecting colorectal recurrence; and (2) a secondary analysis of data from the two arms of the FACS (Follow-up After Colorectal Surgery) trial in which CEA testing was carried out. Setting and participants The secondary analysis was based on data from 582 patients recruited into the FACS trial between 2003 and 2009 from 39 NHS hospitals in England with access to high-volume services offering surgical treatment of metastatic recurrence and followed up for 5 years. CEA testing was undertaken in general practice. Results In the systematic review we identified 52 studies for meta-analysis, including in aggregate 9717 participants (median study sample size 139, interquartile range 72–247). Pooled sensitivity at the most commonly recommended threshold in national guidelines of 5 µg/l was 71% [95% confidence interval (CI) 64% to 76%] and specificity was 88% (95% CI 84% to 92%). In the secondary analysis of FACS data, the diagnostic accuracy of a single CEA test was less than was suggested by the review [area under the receiver operating characteristic curve (AUC) 0.74, 95% CI 0.68 to 0.80]. At the commonly recommended threshold of 5 µg/l, sensitivity was estimated as 50.0% (95% CI 40.1% to 59.9%) and lead time as about 3 months. About four in 10 patients without a recurrence will have at least one false alarm and six out of 10 tests will be false alarms (some patients will have multiple false alarms, particularly smokers). Making decisions to further investigate based on the trend in serial CEA measurements is better (AUC for positive trend 0.85, 95% CI 0.78 to 0.91), but to maintain approximately 70% sensitivity with 90% specificity it is necessary to increase the frequency of testing in year 1 and to apply a reducing threshold for investigation as measurements accrue. Limitations The reference standards were imperfect and the main analysis was subject to work-up bias and had limited statistical precision and no external validation. Conclusions The results suggest that (1) CEA testing should not be used alone as a triage test; (2) in year 1, testing frequency should be increased (to monthly for 3 months and then every 2 months); (3) the threshold for investigating a single test result should be raised to 10 µg/l; (4) after the second CEA test, decisions to investigate further should be made on the basis of the trend in CEA levels; (5) the optimal threshold for investigating the CEA trend falls over time; and (6) continuing smokers should not be monitored with CEA testing. Further research is needed to explore the operational feasibility of monitoring the trend in CEA levels and to externally validate the proposed thresholds for further investigation. Study registration This study is registered as PROSPERO CRD42015019327 and Current Controlled Trials ISRCTN93652154. Funding The main FACS trial and this substudy were funded by the National Institute for Health Research Health Technology Assessment programme

The Diagnosis of Urinary Tract infection in Young children (DUTY): a diagnostic prospective observational study to derive and validate a clinical algorithm for the diagnosis of urinary tract infection in children presenting to primary care with an acute illness

Background: It is not clear which young children presenting acutely unwell to primary care should be investigated for urinary tract infection (UTI) and whether or not dipstick testing should be used to inform antibiotic treatment.Objectives: To develop algorithms to accurately identify pre-school children in whom urine should be obtained; assess whether or not dipstick urinalysis provides additional diagnostic information; and model algorithm cost-effectiveness.Design: Multicentre, prospective diagnostic cohort study.Setting and participants: Children &lt; 5 years old presenting to primary care with an acute illness and/or new urinary symptoms.Methods: One hundred and seven clinical characteristics (index tests) were recorded from the child’s past medical history, symptoms, physical examination signs and urine dipstick test. Prior to dipstick results clinician opinion of UTI likelihood (‘clinical diagnosis’) and urine sampling and treatment intentions (‘clinical judgement’) were recorded. All index tests were measured blind to the reference standard, defined as a pure or predominant uropathogen cultured at ? 105 colony-forming units (CFU)/ml in a single research laboratory. Urine was collected by clean catch (preferred) or nappy pad. Index tests were sequentially evaluated in two groups, stratified by urine collection method: parent-reported symptoms with clinician-reported signs, and urine dipstick results. Diagnostic accuracy was quantified using area under receiver operating characteristic curve (AUROC) with 95% confidence interval (CI) and bootstrap-validated AUROC, and compared with the ‘clinician diagnosis’ AUROC. Decision-analytic models were used toidentify optimal urine sampling strategy compared with ‘clinical judgement’.Results: A total of 7163 children were recruited, of whom 50% were female and 49% were &lt; 2 years old. Culture results were available for 5017 (70%); 2740 children provided clean-catch samples, 94% of whom were ? 2 years old, with 2.2% meeting the UTI definition. Among these, ‘clinical diagnosis’ correctly identified 46.6% of positive cultures, with 94.7% specificity and an AUROC of 0.77 (95% CI 0.71 to 0.83). Four symptoms, three signs and three dipstick results were independently associated with UTI with an AUROC (95% CI; bootstrap-validated AUROC) of 0.89 (0.85 to 0.95; validated 0.88) for symptoms and signs, increasing to 0.93 (0.90 to 0.97; validated 0.90) with dipstick results. Nappy pad samples were provided from the other 2277 children, of whom 82% were &lt; 2 years old and 1.3% met the UTI definition.‘Clinical diagnosis’ correctly identified 13.3% positive cultures, with 98.5% specificity and an AUROC of 0.63 (95% CI 0.53 to 0.72). Four symptoms and two dipstick results were independently associated with UTI, with an AUROC of 0.81 (0.72 to 0.90; validated 0.78) for symptoms, increasing to 0.87 (0.80 to 0.94; validated 0.82) with the dipstick findings. A high specificity threshold for the clean-catch model was more accurate and less costly than, and as effective as, clinical judgement. The additional diagnostic utility of dipstick testing was offset by its costs. The cost-effectiveness of the nappy pad model was not clear-cut.Conclusions: Clinicians should prioritise the use of clean-catch sampling as symptoms and signs can cost-effectively improve the identification of UTI in young children where clean catch is possible. Dipstick testing can improve targeting of antibiotic treatment, but at a higher cost than waiting for a laboratory result. Future research is needed to distinguish pathogens from contaminants, assess the impact of the clean-catch algorithm on patient outcomes, and the cost-effectiveness of presumptive versus dipstick versus laboratory-guided antibiotic treatment.Funding: The National Institute for Health Research Health Technology Assessment programme.<br/

Methodology and reporting of diagnostic accuracy studies of automated perimetry in glaucoma: evaluation using a standardised approach

Purpose: To evaluate methodological and reporting quality of diagnostic accuracy studies of perimetry in glaucoma and to determine whether there had been any improvement since the publication of the Standards for Reporting of Diagnostic Accuracy (STARD) guidelines. Methods: A systematic review of English language articles published between 1993 and 2013 reporting the diagnostic accuracy of perimetry in glaucoma. Articles were appraised for methodological quality using the 14-item Quality assessment tool for diagnostic accuracy studies (QUADAS) and evaluated for quality of reporting by applying the STARD checklist. Results: Fifty-eight articles were appraised. Overall methodological quality of these studies was moderate with a median number of QUADAS items rated as ‘yes’ equal to 9 (out of a maximum of 14) (IQR 7-10). The studies were often poorly reported; median score of STARD items fully reported was 11 out of 25 (IQR 10-14). A comparison of the studies published in 10-year periods before and after the publication of the STARD checklist in 2003 found quality of reporting had not substantially improved. Conclusions: Methodological and reporting quality of diagnostic accuracy studies of perimetry is sub-optimal and appears not to have improved substantially following the development of the STARD reporting guidance. This observation is consistent with previous studies in ophthalmology and in other medical specialities