Pattern Formation in a Spatially Extended Model of Pacemaker Dynamics in Smooth Muscle Cells.

Spatiotemporal patterns are common in biological systems. For electrically coupled cells, previous studies of pattern formation have mainly used applied current as the primary bifurcation parameter. The purpose of this paper is to show that applied current is not needed to generate spatiotemporal patterns for smooth muscle cells. The patterns can be generated solely by external mechanical stimulation (transmural pressure). To do this we study a reaction-diffusion system involving the Morris-Lecar equations and observe a wide range of spatiotemporal patterns for different values of the model parameters. Some aspects of these patterns are explained via a bifurcation analysis of the system without coupling - in particular Type I and Type II excitability both occur. We show the patterns are not due to a Turing instability and that the spatially extended model exhibits spatiotemporal chaos. We also use travelling wave coordinates to analyse travelling waves.

Robust Devaney chaos in the two-dimensional border-collision normal form.

The collection of all non-degenerate, continuous, two-piece, piecewise-linear maps on R2 can be reduced to a four-parameter family known as the two-dimensional border-collision normal form. We prove that throughout an open region of parameter space, this family has an attractor satisfying Devaney's definition of chaos. This strengthens the existing results on the robustness of chaos in piecewise-linear maps. We further show that the stable manifold of a saddle fixed point, despite being a one-dimensional object, densely fills an open region containing the attractor. Finally, we identify a heteroclinic bifurcation, not described previously, at which the attractor undergoes a crisis and may be destroyed.

Streamlined variational inference for higher level group-specific curve models.

A two-level group-specific curve model is such that the mean response of each member of a group is a separate smooth function of a predictor of interest. The three-level extension is such that one grouping variable is nested within another one, and higher level extensions are analogous. Streamlined variational inference for higher level group-specific curve models is a challenging problem. We confront it by systematically working through two-level and then three-level cases and making use of the higher level sparse matrix infrastructure laid down in Nolan and Wand (2019). A motivation is analysis of data from ultrasound technology for which three-level group-specific curve models are appropriate. Whilst extension to the number of levels exceeding three is not covered explicitly, the pattern established by our systematic approach sheds light on what is required for even higher level group-specific curve models.

An unusual presentation of dysarthria in a young patient, a stroke mimic.

Internal carotid artery dissection commonly affects younger patients. We present a case of a previously fit and well 43-year-old gentleman who presented with a sudden onset of slurring of speech, with right-sided tongue deviation and fasciculation on examination. Signs and symptoms began following participation in a home workout class. Magnetic resonance angiography revealed right-sided extracrainal internal carotid artery dissection leading to right-sided unilateral twelfth cranial nerve palsy.

Correlation between biochemical features and outcomes of preoperative imaging (SPECT-CT and Ultrasound) in primary hyperparathyroidism.

Background: Primary hyperparathyroidism is the third most common endocrine disorder, diagnosed by elevated parathyroid hormone (PTH) in hypercalcaemia. Several biochemical factors have been described to suggest severity of disease and may be correlated with preoperative imaging. Methods: This was a retrospective study of patients who underwent parathyroidectomy over a 3-year period. Preoperative calcium, PTH, vitamin D levels, ALP (alkaline phosphatase), vitamin D, serum phosphate and US and SPECT-CT positivity was noted. Results: 176 patients underwent parathyroidectomy and these were divided into 4 groups based on preoperative calcium. Overall, 61% of patients showed concordance between imaging and operative findings. Severe hypercalcaemia was associated with higher PTH levels, lower vitamin D levels, an increased rate of abnormal ALP levels, lower phosphate, male gender and highest rate of imaging concordance. Imaging positivity was associated with severe hypercalcaemia and elevated PTH levels. Level of PTH >125 pmol/L and hypercalcaemia >2.8 mmol/L are the most accurate cut-off levels for scan positivity. Conclusion: Biochemical factors associated with severity of the disease are directly correlated with positivity of preoperative imaging while ALP and vitamin D did not influence the preoperative imaging positivity but are associated with disease adversity. Serum phosphate level independently predicted results of parathyroid US.

Numerical Bifurcation Analysis of Pacemaker Dynamics in a Model of Smooth Muscle Cells.

Evidence from experimental studies shows that oscillations due to electro-mechanical coupling can be generated spontaneously in smooth muscle cells. Such cellular dynamics are known as pacemaker dynamics. In this article, we address pacemaker dynamics associated with the interaction of [Formula: see text] and [Formula: see text] fluxes in the cell membrane of a smooth muscle cell. First we reduce a pacemaker model to a two-dimensional system equivalent to the reduced Morris-Lecar model and then perform a detailed numerical bifurcation analysis of the reduced model. Existing bifurcation analyses of the Morris-Lecar model concentrate on external applied current, whereas we focus on parameters that model the response of the cell to changes in transmural pressure. We reveal a transition between Type I and Type II excitabilities with no external current required. We also compute a two-parameter bifurcation diagram and show how the transition is explained by the bifurcation structure.

Microscopic Imaging of the Stress Tensor in Diamond Using in Situ Quantum Sensors.

The precise measurement of mechanical stress at the nanoscale is of fundamental and technological importance. In principle, all six independent variables of the stress tensor, which describe the direction and magnitude of compression/tension and shear stress in a solid, can be exploited to tune or enhance the properties of materials and devices. However, existing techniques to probe the local stress are generally incapable of measuring the entire stress tensor. Here, we make use of an ensemble of atomic-sized in situ strain sensors in diamond (nitrogen-vacancy defects) to achieve spatial mapping of the full stress tensor, with a submicrometer spatial resolution and a sensitivity of the order of 1 MPa (10 MPa) for the shear (axial) stress components. To illustrate the effectiveness and versatility of the technique, we apply it to a broad range of experimental situations, including mapping the stress induced by localized implantation damage, nanoindents, and scratches. In addition, we observe surprisingly large stress contributions from functional electronic devices fabricated on the diamond and also demonstrate sensitivity to deformations of materials in contact with the diamond. Our technique could enable in situ measurements of the mechanical response of diamond nanostructures under various stimuli, with potential applications in strain engineering for diamond-based quantum technologies and in nanomechanical sensing for on-chip mass spectroscopy.

Measuring depth of anaesthesia using changes in directional connectivity: a comparison with auditory middle latency response and estimated bispectral index during propofol anaesthesia.

General anaesthesia is associated with changes in connectivity between different regions of the brain, the assessment of which has the potential to provide a novel marker of anaesthetic effect. We propose an index that quantifies the strength and direction of information flow in electroencephalographic signals collected across the scalp, assess its performance in discriminating 'wakefulness' from 'anaesthesia', and compare it with estimated bispectral index and the auditory middle latency response. We used a step-wise slow induction of anaesthesia in 10 patients to assess graded changes in electroencephalographic directional connectivity at propofol effect-site concentrations of 2 µg.ml-1 , 3 µg.ml-1 and 4 µg.ml-1 . For each stable effect-site concentration, connectivity was estimated from multichannel electroencephalograms using directed coherence, together with middle latency response and estimated bispectral index. We used a linear support vector machine classifier to compare the performance of the different electroencephalographic features in discriminating wakefulness from anaesthesia. We found a significant reduction in the strength of long-range connectivity (interelectrode distance > 10 cm) (p < 0.008), and a reversal of information flow from markedly postero-frontal to fronto-posterior (p < 0.006) between wakefulness and a propofol effect-site concentration of 2 µg.ml-1 . This then remained relatively constant as effect-site concentration increased, consistent with a step change in directed coherence with anaesthesia. This contrasted with the gradual change with increasing anaesthetic dose observed for estimated bispectral index and middle latency response. Directed coherence performed best in discriminating wakefulness from anaesthesia with an accuracy of 95%, indicating the potential of this new method (on its own or combined with others) for monitoring adequacy of anaesthesia.

A group sequential test for ABR detection.

Objective: To detect the auditory brainstem response (ABR) automatically using an innovative sequentially applied Hotelling's T 2 test, with the overall goal of optimising test time whilst controlling the false-positive rate (FPR). Design: The stage-wise critical decision boundaries for accepting or rejecting the null hypothesis were found using a new approach called the Convolutional Group Sequential Test (CGST). Specificity, sensitivity, and test time were evaluated using simulations and subject recorded data. Study sample: Data consists of click-evoked ABR threshold series from 12 normal hearing adults, and recordings of EEG background activity from 17 normal hearing adults. Results: Reductions in mean test time of up to 40-45% were observed for the sequential test, relative to a conventional "single shot" test where the statistical test is applied to the data just once. To obtain these results, it will occasionally be necessary to run the test to a higher number of stimuli, i.e. the maximum test time needs to be increased. Conclusions: The CGST can be used to control the specificity of a sequentially applied ABR detection method. Doing so can reduce test time, relative to the "single shot" test, when considered across a cohort of test subjects.

A general framework for boundary equilibrium bifurcations of Filippov systems.

As parameters are varied, a boundary equilibrium bifurcation (BEB) occurs when an equilibrium collides with a discontinuity surface in a piecewise-smooth system of ordinary differential equations. Under certain genericity conditions, at a BEB, the equilibrium either transitions to a pseudo-equilibrium (on the discontinuity surface) or collides and annihilates with a coexisting pseudo-equilibrium. These two scenarios are distinguished by the sign of a certain inner product. Here, it is shown that this sign can be determined from the number of unstable directions associated with the two equilibria by using techniques developed by Feigin. A normal form is proposed for BEBs in systems of any number of dimensions. The normal form involves a companion matrix, as does the leading order sliding dynamics, and so the connection to the stability of the equilibria is explicit. In two dimensions, the parameters of the normal form distinguish, in a simple way, the eight topologically distinct cases for the generic local dynamics at a BEB. A numerical exploration in three dimensions reveals that BEBs can create multiple attractors and chaotic attractors and that the equilibrium at the BEB can be unstable even if both equilibria are stable. The developments presented here stem from seemingly unutilised similarities between BEBs in discontinuous systems (specifically Filippov systems as studied here) and BEBs in continuous systems for which analogous results are, to date, more advanced.

Objective measures for detecting the auditory brainstem response: comparisons of specificity, sensitivity and detection time.

OBJECTIVE: To evaluate and compare the specificity, sensitivity and detection time of various time-domain and multi-band frequency domain methods when detecting the auditory brainstem response (ABR). DESIGN: Simulations and subject recorded data were used to assess and compare the performance of the Hotelling's T2 test (applied in either time or frequency domain), two versions of the modified q-sample uniform scores test and both the Fsp and Fmp, which were evaluated using both conventional F-distributions with assumed degrees of freedom and a bootstrap approach. STUDY SAMPLE: Data consisted of click-evoked ABRs and recordings of EEG background activity from 12 to 17 normal hearing adults, respectively. RESULTS: An overall advantage in sensitivity and detection time was demonstrated for the Hotelling's T2 test. The false-positive rates (FPRs) of the Fsp and Fmp were also closer to the nominal alpha-level when evaluating statistical significance using the bootstrap approach, as opposed to using conventional F-distributions. The FPRs of the remaining methods were slightly higher than expected. CONCLUSIONS: In this work, Hotelling's T2 outperformed the alternative methods for automatically detecting ABRs. Its promise as a sensitive and efficient detection method should now be tested in a larger clinical study.

Unfolding homoclinic connections formed by corner intersections in piecewise-smooth maps.

The stable and unstable manifolds of an invariant set of a piecewise-smooth map are themselves piecewise-smooth. Consequently, as parameters of a piecewise-smooth map are varied, an invariant set can develop a homoclinic connection when its stable manifold intersects a non-differentiable point of its unstable manifold (or vice-versa). This is a codimension-one bifurcation analogous to a homoclinic tangency of a smooth map, referred to here as a homoclinic corner. This paper presents an unfolding of generic homoclinic corners for saddle fixed points of planar piecewise-smooth continuous maps. It is shown that a sequence of border-collision bifurcations limits to a homoclinic corner and that all nearby periodic solutions are unstable.

The role of chemisorbed hydroxyl species in alkaline electrocatalysis of glycerol on gold.

The mechanism of energy conversion in a direct glycerol fuel cell (DGFC) is governed by the anode supported heterogeneous steps of glycerol electro-oxidation. In aerated alkaline electrolytes, glycerol also participates in a base catalyzed process, which can release certain species mixing with the anode catalyzed surface products. As a result, selective probing of the surface catalytic reactions involving such systems can be difficult. The present work addresses this issue for a gold anode by using the analytical capability of cyclic voltammetry (CV). In addition, surface plasmon resonance measurements are used to optically probe the adsorption characteristics of the electrolyte species. The net exchange current of the oxidation process and the transfer coefficient of the rate determining step are evaluated by analyzing the CV data. The interfacial reactions and their products on Au are identified by measuring the number of electrons released during the electro-oxidation of glycerol. The results indicate that these reactions are facilitated by the surface bound hydroxyl species on Au (chemisorbed OH(-) and faradaically formed Au-OH). By comparing the findings for stationary and rotating electrodes, it is shown that, convective mass transport is critical to maintaining efficient progression of the consecutive oxidation steps of glycerol. In the absence of hydrodynamic support, the main surface products of glycerol oxidation appear to be glyceraldehyde, glycerate and malonate, formed through a net six-electron route. In the presence of controlled convection, a ten-electron process is activated, where mesaxolate is the likely additional product.

Venous thromboembolism rates in patients undergoing major hip and knee joint surgery at Waitemata District Health Board: a retrospective audit.

BACKGROUND/AIM: Symptomatic venous thromboembolism (VTE) complicates approximately 4% of major orthopaedic surgical procedures performed without thromboprophylaxis. Randomised clinical trials demonstrate primary thromboprophylaxis reduces VTE rates to <1%, with low rates of clinically important bleeding, using low molecular weight heparin (LMWH), oral FXa inhibitors or thrombin inhibitors. We reviewed the rates of VTE in patients undergoing major hip/knee joint surgery at Waitemata District Health Board (WDHB). METHODS: Cases of VTE within 90 days of orthopaedic surgery were identified by retrospective audit of data from the haematology VTE database. The number of major hip/knee joint surgeries at WDHB from January 2006 to December 2010 was obtained from clinical coding data. RESULTS: The cumulative incidence of VTE within 90 days of surgery was 3.29%. The median time from surgery to diagnosis was 7 days. Deep vein thrombosis comprised 75% of cases, 77.6% distal and 23.2% proximal. Pulmonary embolism comprised 26.5% of VTE; 47.7% had right heart strain on computed tomography/echocardiography. Hip fracture surgery comprised one-third of patients. Of patients developing VTE, 85.5% had chemical thromboprophylaxis - aspirin 73%, LMWH 20 mg 16%, LMWH 40 mg 16%, therapeutic LMWH 3%, unfractionated heparin twice daily 1%, and warfarin 4%; 75.6% received mechanical prophylaxis, while 4% of patients received no prophylaxis. CONCLUSION: VTE incidence after major hip/knee joint surgery at WDHB is high, with pulmonary embolism comprising almost one-third of all VTE in this study, indicating the prophylaxis given is suboptimal. Implementation of appropriate, extended duration prophylaxis as per evidence-based guidelines is required to reduce these rates.

Management and outcomes of axial isolated distal deep vein thrombosis at North Shore Hospital, New Zealand: a retrospective audit.

BACKGROUND: It is standard of care to treat proximal vein deep vein thrombosis (DVT) for a minimum of 3 months. Conversely, management of isolated distal DVT (IDDVT) is controversial, with options including observation and repeat ultrasound scan within 1 week to detect and anticoagulate those with proximal propagation, or anticoagulation for periods of up to 3 months. AIM: The aim was to assess the rates of proximal propagation and venous thromboembolism (VTE) recurrence within 3 months of diagnosis of IDDVT, and to examine how the duration of treatment might influence this. METHODS: Study patients were identified by retrospective audit of data from the North Shore Hospital VTE database. All patients presenting with established axial vein distal DVT from July 2007 to June 2012 were included. A 6-week treatment duration cut-off was used to separate the treatment arms (<6 weeks vs 6 weeks vs >6 weeks), and Fisher's exact or Pearson's Chi-squared tests were used to assess between-group comparisons. RESULTS: Five hundred and seven patients were included in the study, mean age 59.7 years; 53% female. There were three cases of proximal propagation, all occurring in those receiving <6 weeks treatment. There were six VTE recurrences, three in the <6 week and three in the ≥6 week treatment groups respectively. Malignancy was the only significant predictor of VTE recurrence (P = 0.001). CONCLUSION: A 6-week duration of anticoagulation appears to be an effective and safe treatment for isolated axial distal DVT, with low rates of VTE recurrence and proximal propagation.

Brain morphometric correlates of metabolic variables in HIV: the CHARTER study.

Obesity and other metabolic variables are associated with abnormal brain structural volumes and cognitive dysfunction in HIV-uninfected populations. Since individuals with HIV infection on combined antiretroviral therapy (CART) often have systemic metabolic abnormalities and changes in brain morphology and function, we examined associations among brain volumes and metabolic factors in the multisite CNS HIV AntiRetroviral Therapy Effects Research (CHARTER) cohort, cross-sectional study of 222 HIV-infected individuals. Metabolic variables included body mass index (BMI), total blood cholesterol (C), low- and high-density lipoprotein C (LDL-C and HDL-C), blood pressure, random blood glucose, and diabetes. MRI measured volumes of cerebral white matter, abnormal white matter, cortical and subcortical gray matter, and ventricular and sulcal CSF. Multiple linear regression models allowed us to examine metabolic variables separately and in combination to predict each regional volume. Greater BMI was associated with smaller cortical gray and larger white matter volumes. Higher total cholesterol (C) levels were associated with smaller cortex volumes; higher LDL-C was associated with larger cerebral white matter volumes, while higher HDL-C levels were associated with larger sulci. Higher blood glucose levels and diabetes were associated with more abnormal white matter. Multiple atherogenic metabolic factors contribute to regional brain volumes in HIV-infected, CART-treated patients, reflecting associations similar to those found in HIV-uninfected individuals. These risk factors may accelerate cerebral atherosclerosis and consequent brain alterations and cognitive dysfunction.

One-dimensional transport of bosons between weakly linked reservoirs.

We study a flow of ultracold bosonic atoms through a one-dimensional channel that connects two macroscopic three-dimensional reservoirs of Bose-condensed atoms via weak links implemented as potential barriers between each of the reservoirs and the channel. We consider reservoirs at equal chemical potentials so that a superflow of the quasicondensate through the channel is driven purely by a phase difference 2Φ imprinted between the reservoirs. We find that the superflow never has the standard Josephson form ∼sin2Φ. Instead, the superflow discontinuously flips direction at 2Φ=±π and has metastable branches. We show that these features are robust and not smeared by fluctuations or phase slips. We describe a possible experimental setup for observing these phenomena.

Management and outcomes of single subsegmental pulmonary embolus: a retrospective audit at North Shore Hospital, New Zealand.

BACKGROUND: It is unknown whether filling defects in subsegmental arteries on multidetector computed tomography pulmonary angiography correlate with clinically relevant subsegmental pulmonary embolism (PE) on pulmonary angiography. Current guidelines do not differentiate between PE in segmental and subsegmental vessels, and many patients receive at least 3 months anticoagulation. The strategy employed at North Shore Hospital in haemodynamically stable patients with single subsegmental PE is to perform bilateral lower leg compression ultrasound (CUS). Anticoagulation is withheld if CUS is negative; a bilateral CUS is repeated in 7-10 days. AIM: The aim of this retrospective audit was to ensure our current management strategy is safe. METHODS: All diagnoses of single subsegmental PE between June 2005 and June 2013 were included. The primary outcome was the rate of venous thromboembolism (VTE) recurrence within 3 months of single subsegmental PE diagnosis. Secondary outcomes were rates of major/minor bleeding and all-cause mortality. RESULTS: Thirty-two patients were included - 20 were treated with anticoagulation; 12 were managed with observation/serial bilateral lower limb CUS. None of the patients in either group had VTE recurrence by 3 months. No bleeding episodes were observed in the observation group; there was a 10% major bleeding rate (n = 2) in the treatment group. One death occurred in each group, neither of which was attributed to VTE. CONCLUSION: Withholding anticoagulation in patients with single subsegmental PE and negative serial bilateral CUS appears to be a safe and effective management strategy, with a low risk of VTE recurrence.

Gaussian Processes for Hearing Threshold Estimation Using Auditory Brainstem Responses.

The Auditory Brainstem Response (ABR) plays an important role in diagnosing and managing hearing loss, but can be challenging and time-consuming to measure. Test times are especially long when multiple ABR measurements are needed, e.g., when estimating hearing threshold at a range of frequencies. While many detection methods have been developed to reduce ABR test times, the majority were designed to detect the ABR at a single stimulus level and do not consider correlations in ABR waveforms across levels. These correlations hold valuable information, and can be exploited for more efficient hearing threshold estimation. This was achieved in the current work using a Gaussian Process (GP), i.e., a Bayesian approach for non-linear regression. The function to estimate with the GP was the ABR's amplitude across stimulus levels, from which hearing threshold was ultimately inferred. Active learning rules were also designed to automatically adjust the stimulus level and efficiently locate hearing threshold. Simulation results show test time reductions of up to  âˆ¼ 50% for the GP compared to a sequentially applied Hotelling's T2 test, which does not consider correlations across ABR waveforms. A case study was also included to briefly assess the GP approach in ABR data from an adult volunteer.

Apolipoprotein E4 genotype does not increase risk of HIV-associated neurocognitive disorders.

This is a cross-sectional, observational study to evaluate the hypothesis that HIV-seropositive (HIV+) apolipoprotein E4 (APOE4) carriers are at increased risk for HIV-associated neurocognitive disorders (HAND) compared to APOE4 noncarriers with HIV in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) Group sample. APOE genotype was determined in 466 CHARTER participants with varying disease stages and histories of antiretroviral treatment who did not have severe psychiatric or medical comorbid conditions that preclude diagnosis of HAND. HAND diagnoses were based on results of comprehensive neurobehavioral evaluation and use of current neuroAIDS diagnostic criteria. HAND status consists of two levels: neuropsychologically normal status (i.e., no HAND) and any HAND diagnosis (i.e., asymptomatic neurocognitive impairment, minor neurocognitive disorder, HIV-associated dementia). Logistic regression analyses revealed no association between APOE4 carrier status and HAND, and there were no interactions between APOE4 carrier status and ethnicity, age, substance use disorders, duration of infection, or nadir CD4. Results did not differ when analysis was restricted to symptomatic HAND, and no APOE4 gene dose-dependent relationship to HAND emerged. APOE4 status was not associated with concurrent HAND in this large, well-characterized sample. This does not preclude emergence of an association between APOE4 status and HAND as this population ages. Prospective, longitudinal studies are needed to examine APOE4 as a risk factor for neurocognitive decline, incident HAND at older ages, and potential associations with cerebrospinal fluid amyloid.