Hypercapnia-induced vasodilation in the cerebral circulation is reduced in older adults with sleep-disordered breathing.

The prevalence of sleep-disordered breathing (SDB) is higher in older adults compared with younger individuals. The increased propensity for ventilatory control instability in older adults may contribute to the increased prevalence of central apneas. Reductions in the cerebral vascular response to CO2 may exacerbate ventilatory overshoots and undershoots during sleep. Thus, we hypothesized that hypercapnia-induced cerebral vasodilation (HCVD) will be reduced in older compared with younger adults. In 11 older and 10 younger adults with SDB, blood flow velocity in the middle cerebral artery (MCAV) was measured using Doppler transcranial ultrasonography during multiple steady-state hyperoxic hypercapnic breathing trials while awake, interspersed with room air breathing. Changes in ventilation, MCAV, and mean arterial pressure (MAP) via finger plethysmography during the trials were compared with baseline eupneic values. For each hyperoxic hypercapnic trial, the change (Δ) in MCAV for a corresponding change in end-tidal CO2 and the HCVD or the change in cerebral vascular conductance (MCAV divided by MAP) for a corresponding change in end-tidal CO2 was determined. The hypercapnic ventilatory response was similar between the age groups, as was ΔMCAV/Δ[Formula: see text]. However, compared with young, older adults had a significantly smaller HCVD (1.3 ± 0.7 vs. 2.1 ± 0.6 units/mmHg, P = 0.004). Multivariable analyses demonstrated that age and nadir oxygen saturation during nocturnal polysomnography were significant predictors of HCVD. Thus, our data indicate that older age and SDB-related hypoxia are associated with diminished HCVD. We hypothesize that this impairment in vascular function may contribute to breathing instability during sleep in these individuals.NEW & NOTEWORTHY This study demonstrates, for the first time, in individuals with sleep-disordered breathing (SDB) that aging is associated with decreased hypercapnia-induced cerebral vasodilation (HCVD). In addition to advanced age, the magnitude of nocturnal oxygen desaturation due to SDB is an equal independent predictor of HCVD.

Drone-based imaging to assess the microbial water quality in an irrigation pond: A pilot study.

Microbial water quality datasets are essential in irrigated agricultural practices to detect and inform measures to prevent the contamination of produce. Escherichia coli (E. coli) concentrations are commonly used to evaluate microbial water quality. Remote sensing imagery has been successfully used to retrieve several water quality parameters that can be determinants of E. coli habitats in waterbodies. This pilot study was conducted to test the possibility of using imagery from a small unmanned aerial vehicle (sUAV or drone) to improve the estimation of microbial water quality in small irrigation ponds. In situ measurements of pH, turbidity, specific conductance, and concentrations of dissolved oxygen, chlorophyll-a, phycocyanin, and fluorescent dissolved organic matter were taken at depths of 0-15 cm in 23 locations across a pond in Central Maryland, USA. The pond surface was concurrently imaged using a drone with three modified GoPro cameras, and a multispectral MicaSense RedEdge camera with five spectral bands. The GoPro imagery was decomposed into red, blue, and green components. Mean digital numbers for 1-m radius areas in the images were combined with the water quality data to provide input for a regression tree-based analysis. The accuracy of the regression-tree data description with "only imagery" inputs was the same or better than that of trees constructed with "only water-quality parameters" as inputs. From multiple cross-validation runs with "only imagery" inputs for the regression trees, the average (±SD) determination coefficient and root-mean-squared error of the decimal logarithm of E. coli concentrations were 0.793 ±â€¯0.035 and 0.131 ±â€¯0.011, respectively. The results of this study demonstrate the opportunities for using sUAV imagery for obtaining a more accurate delineation of the spatial variation of E. coli concentrations in irrigation ponds.

Exact inference for integrated population modelling.

Integrated population modelling is widely used in statistical ecology. It allows data from population time series and independent surveys to be analysed simultaneously. In classical analysis the time-series likelihood component can be conveniently approximated using Kalman filter methodology. However, the natural way to model systems which have a discrete state space is to use hidden Markov models (HMMs). The proposed method avoids the Kalman filter approximations and Monte Carlo simulations. Subject to possible numerical sensitivity analysis, it is exact, flexible, and allows the use of standard techniques of classical inference. We apply the approach to data on Little owls, where the model is shown to require a one-dimensional state space, and Northern lapwings, with a two-dimensional state space. In the former example the method identifies a parameter redundancy which changes the perception of the data needed to estimate immigration in integrated population modelling. The latter example may be analysed using either first- or second-order HMMs, describing numbers of one-year olds and adults or adults only, respectively. The use of first-order chains is found to be more efficient, mainly due to the smaller number of one-year olds than adults in this application. For the lapwing modelling it is necessary to group the states in order to reduce the large dimension of the state space. Results check with Bayesian and Kalman filter analyses, and avenues for future research are identified.

Understanding the electronic structure of IrO2 using hard-X-ray photoelectron spectroscopy and density-functional theory.

The electronic structure of IrO2 has been investigated using hard x-ray photoelectron spectroscopy and density-functional theory. Excellent agreement is observed between theory and experiment. We show that the electronic structure of IrO2 involves crystal field splitting of the iridium 5d orbitals in a distorted octahedral field. The behavior of IrO2 closely follows the theoretical predictions of Goodenough for conductive rutile-structured oxides [J. B. Goodenough, J. Solid State Chem. 3, 490 (1971).

Absence of a space-charge-derived enhancement of ionic conductivity in ß|γ- heterostructured 7H- and 9R-AgI.

Extreme room temperature conductivity enhancements have been reported for nanocrystalline AgI of up to  × 10(4) relative to bulk ß-AgI (Guo et al 2005 Adv. Mater. 17 2815-9). These samples were identified as possessing 7H and 9R polytype structures, which can be considered as heterostructures composed of thin, commensurate layers in the ß (wurtzite) and γ (zincblende) phases. It has been proposed that space-charge layer formation at ß|γ-interfaces causes near complete disordering of the Ag(+) sublattice in these polytypes, resulting in a massive intrinsic enhancement of ionic conductivity. We have performed molecular dynamics simulations of ß- and γ-AgI and mixed ß|γ superlattices, to study the effect of heterostructuring on intrinsic defect populations and Ag(+) transport. The ionic conductivities and Ag(+) diffusion coefficients vary as ß > 7H ≈ 9R ≈ 10L > Î³. The ß|γ-heterostructured polytypes show no enhancement in defect populations or Ag(+) mobilities relative to the ß-AgI phase, and instead behave as simple composites of ß- and γ-AgI. This contradicts the proposal that the extreme conductivity enhancement observed for 7H and 9R polytypes is explained by extensive space-charge formation.

Chemical bonding in copper-based transparent conducting oxides: CuMO2 (M = In, Ga, Sc).

The geometry and electronic structure of copper-based p-type delafossite transparent conducting oxides, CuMO(2) (M = In, Ga, Sc), are studied using the generalized gradient approximation (GGA) corrected for on-site Coulomb interactions (GGA + U). The bonding and valence band compositions of these materials are investigated, and the origins of changes in the valence band features between group 3 and group 13 cations are discussed. Analysis of the effective masses at the valence and conduction band edge explains the experimentally reported conductivity trends.

Kinetic models of guanidine hydrochloride-induced curing of the yeast [PSI+] prion.

A population of [PSI(+)] Saccharomyces cerevisiae cells can be cured of the [PSI(+)] prion by the addition of guanidine hydrochloride (GdnHCl). In this paper we extend existing nucleated polymerisation simulation models to investigate the mechanisms that might underlie curing. Our results are consistent with the belief that prions are dispersed through the cells at division following GdnHCl addition. A key feature of the simulation model is that the probability that a polymer is transmitted from mother to daughter during cell division is dependent upon the length of the polymer. The model is able to reproduce the essential features of data from several different experimental protocols involving addition and removal of GdnHCl.

Determining the parametric structure of models.

In this paper we develop a comprehensive approach to determining the parametric structure of models. This involves considering whether a model is parameter redundant or not and investigating model identifiability. The approach adopted makes use of exhaustive summaries, quantities that uniquely define the model. We review and generalise previous work on evaluating the symbolic rank of an appropriate derivative matrix to detect parameter redundancy, and then develop further tools for use within this framework, based on a matrix decomposition. Complex models, where the symbolic rank is difficult to calculate, may be simplified structurally using reparameterisation and by finding a reduced-form exhaustive summary. The approach of the paper is illustrated using examples from ecology, compartment modelling and Bayes networks. This work is topical as models in the biosciences and elsewhere are becoming increasingly complex.

Modeling survival at multi-population scales using mark-recapture data.

The demography of vertebrate populations is governed in part by processes operating at large spatial scales that have synchronizing effects on demographic parameters over large geographic areas, and in part, by local processes that generate fluctuations that are independent across populations. We describe a statistical model for the analysis of individual monitoring data at the multi-population scale that allows us to (1) split up temporal variation in survival into two components that account for these two types of processes and (2) evaluate the role of environmental factors in generating these two components. We derive from this model an index of synchrony among populations in the pattern of temporal variation in survival, and we evaluate the extent to which environmental factors contribute to synchronize or desynchronize survival variation among populations. When applied to individual monitoring data from four colonies of the Atlantic Puffin (Fratercula arctica), 67% of between-year variance in adult survival was accounted for by a global spatial-scale component, indicating substantial synchrony among colonies. Local sea surface temperature (SST) accounted for 40% of the global spatial-scale component but also for an equally large fraction of the local-scale component. SST thus acted at the same time as both a synchronizing and a desynchronizing agent. Between-year variation in adult survival not explained by the effect of local SST was as synchronized as total between-year variation, suggesting that other unknown environmental factors acted as synchronizing agents. Our approach, which focuses on demographic mechanisms at the multi-population scale, ideally should be combined with investigations of population size time series in order to characterize thoroughly the processes that underlie patterns of multi-population dynamics and, ultimately, range dynamics.

Approximations for expected generation number.

A deterministic formula is commonly used to approximate the expected generation number of a population of growing cells. However, this can give misleading results because it does not allow for natural variation in the times that individual cells take to reproduce. Here we present more accurate approximations for both symmetric and asymmetric cell division. Based on the first two moments of the generation time distribution, these approximations are also robust. We illustrate the improved approximations using data that arise from monitoring individual yeast cells under a microscope and also demonstrate how the approximations can be used when such detailed data are not available.

New approximations to the Malthusian parameter.

Approximations to the Malthusian parameter of an age-dependent branching process are obtained in terms of the moments of the lifetime distribution, by exploiting a link with renewal theory. In several examples, the new approximations are more accurate than those currently in use, even when based on only the first two moments. The new approximations are extended to include a form of asymmetric cell division that occurs in some species of yeast. When used for inference, the new approximations are shown to have high efficiency.

Semiparametric regression in capture-recapture modeling.

Capture-recapture models were developed to estimate survival using data arising from marking and monitoring wild animals over time. Variation in survival may be explained by incorporating relevant covariates. We propose nonparametric and semiparametric regression methods for estimating survival in capture-recapture models. A fully Bayesian approach using Markov chain Monte Carlo simulations was employed to estimate the model parameters. The work is illustrated by a study of Snow petrels, in which survival probabilities are expressed as nonlinear functions of a climate covariate, using data from a 40-year study on marked individuals, nesting at Petrels Island, Terre Adélie.

Factors influencing soay sheep survival: a Bayesian analysis.

This article presents a Bayesian analysis of mark-recapture-recovery data on Soay sheep. A reversible jump Markov chain Monte Carlo technique is used to determine age classes of common survival, and to model the survival probabilities in those classes using logistic regression. This involves environmental and individual covariates, as well as random effects. Auxiliary variables are used to impute missing covariates measured on individual sheep. The Bayesian approach suggests different models from those previously obtained using classical statistical methods. Following model averaging, features that were not previously detected, and which are of ecological importance, are identified.

Estimating the number of prions in yeast cells.

Certain yeast cells contain proteins that behave like the mammalian prion PrP and are called yeast prions. The yeast prion protein Sup35p can exist in one of two stable forms, giving rise to phenotypes [PSI(+)] and [psi(-)]. If the chemical guanidine hydrochloride (GdnHCl) is added to a culture of growing [PSI(+)] cells, the proportion of [PSI(+)] cells decreases over time. This process is called curing and is due to a failure to propagate the prion form of Sup35p. We describe how curing can be modelled, and improve upon previous models for the underlying processes of cell division and prion segregation; the new model allows for asymmetric cell division and unequal prion segregation. We conclude by outlining plans for future experimentation and modelling.

Models for yeast prions.

The cytoplasmic heritable determinant [PSI+] of the yeast Saccharomyces cerevisiae exhibits prion-like properties. The properties of yeast prions are studied in the hope that this will enhance the understanding of mammalian prions, which cause mad-cow, Creutzfeldt-Jakob, and related neurodegenerative diseases. When host cells divide, the yeast prions distribute themselves without loss over the daughter cells. Experimental data provide information on how the proportion of cells with prions decreases over time when priori replication is inhibited. One feature of scientific interest is the unknown mean number, n0, of prions assumed to be present in the cells at the start of the experiment. We develop several stochastic models and by fitting them to the data, we obtain substantially larger estimates of n0 compared with a previous analysis. An interesting feature of a model with constant cell generation times is that the predicted proportion of cells with prions varies over time as a sequence of linked hyperbolic curves. Avenues for future research are outlined, which relax simplifying assumptions made in the models. We make several recommendations for the design of future experiments.

The analysis of ring-recovery data using random effects.

We show how random terms, describing both yearly variation and overdispersion, can easily be incorporated into models for mark-recovery data, through the use of Bayesian methods. For recovery data on lapwings, we show that the incorporation of the random terms greatly improves the goodness of fit. Omitting the random terms can lead to overestimation of the significance of weather on survival, and overoptimistic prediction intervals in simulations of future population behavior. Random effects models provide a natural way of modeling overdispersion-which is more satisfactory than the standard classical approach of scaling up all standard errors by a uniform inflation factor. We compare models by means of Bayesian p-values and the deviance information criterion (DIC).

Integrating mark-recapture-recovery and census data to estimate animal abundance and demographic parameters.

In studies of wild animals, one frequently encounters both census and mark-recapture-recovery data. We show how a state-space model for census data in combination with the usual multinomial-based models for ring-recovery data provide estimates of productivity not available from either type of data alone. The approach is illustrated on two British bird species. For the lapwing, we calibrate how its recent decline could be due to a decrease in productivity. For the heron, there is no evidence for a decline in productivity, and the combined analysis increases significantly the strength of logistic regressions of survival on winter severity.

Fatiguing inspiratory muscle work causes reflex reduction in resting leg blood flow in humans.

1. We recently showed that fatigue of the inspiratory muscles via voluntary efforts caused a time-dependent increase in limb muscle sympathetic nerve activity (MSNA) (St Croix et al. 2000). We now asked whether limb muscle vasoconstriction and reduction in limb blood flow also accompany inspiratory muscle fatigue. 2. In six healthy human subjects at rest, we measured leg blood flow (.Q(L)) in the femoral artery with Doppler ultrasound techniques and calculated limb vascular resistance (LVR) while subjects performed two types of fatiguing inspiratory work to the point of task failure (3-10 min). Subjects inspired primarily with their diaphragm through a resistor, generating (i) 60 % maximal inspiratory mouth pressure (P(M)) and a prolonged duty cycle (T(I)/T(TOT) = 0.7); and (ii) 60 % maximal P(M) and a T(I)/T(TOT) of 0.4. The first type of exercise caused prolonged ischaemia of the diaphragm during each inspiration. The second type fatigued the diaphragm with briefer periods of ischaemia using a shorter duty cycle and a higher frequency of contraction. End-tidal P(CO2) was maintained by increasing the inspired CO(2) fraction (F(I,CO2)) as needed. Both trials caused a 25-40 % reduction in diaphragm force production in response to bilateral phrenic nerve stimulation. 3. .Q(L) and LVR were unchanged during the first minute of the fatigue trials in most subjects; however, .Q(L) subsequently decreased (-30 %) and LVR increased (50-60 %) relative to control in a time-dependent manner. This effect was present by 2 min in all subjects. During recovery, the observed changes dissipated quickly (< 30 s). Mean arterial pressure (MAP; +4-13 mmHg) and heart rate (+16-20 beats min(-1)) increased during fatiguing diaphragm contractions. 4. When central inspiratory motor output was increased for 2 min without diaphragm fatigue by increasing either inspiratory force output (95 % of maximal inspiratory pressure (MIP)) or inspiratory flow rate (5 x eupnoea), .Q(L), MAP and LVR were unchanged; although continuing the high force output trials for 3 min did cause a relatively small but significant increase in LVR and a reduction in .Q(L). 5. When the breathing pattern of the fatiguing trials was mimicked with no added resistance, LVR was reduced and .Q(L) increased significantly; these changes were attributed to the negative feedback effects on MSNA from augmented tidal volume. 6. Voluntary increases in inspiratory effort, in the absence of diaphragm fatigue, had no effect on .Q(L) and LVR, whereas the two types of diaphragm-fatiguing trials elicited decreases in .Q(L) and increases in LVR. We attribute these changes to a metaboreflex originating in the diaphragm. Diaphragm and forearm muscle fatigue showed very similar time-dependent effects on LVR and .Q(L).

Exposure to hypoxia produces long-lasting sympathetic activation in humans.

The relative contributions of hypoxia and hypercapnia in causing persistent sympathoexcitation after exposure to the combined stimuli were assessed in nine healthy human subjects during wakefulness. Subjects were exposed to 20 min of isocapnic hypoxia (arterial O(2) saturation, 77-87%) and 20 min of normoxic hypercapnia (end-tidal P(CO)(2), +5.3-8.6 Torr above eupnea) in random order on 2 separate days. The intensities of the chemical stimuli were manipulated in such a way that the two exposures increased sympathetic burst frequency by the same amount (hypoxia: 167 +/- 29% of baseline; hypercapnia: 171 +/- 23% of baseline). Minute ventilation increased to the same extent during the first 5 min of the exposures (hypoxia: +4.4 +/- 1.5 l/min; hypercapnia: +5.8 +/- 1.7 l/min) but declined with continued exposure to hypoxia and increased progressively during exposure to hypercapnia. Sympathetic activity returned to baseline soon after cessation of the hypercapnic stimulus. In contrast, sympathetic activity remained above baseline after withdrawal of the hypoxic stimulus, even though blood gases had normalized and ventilation returned to baseline levels. Consequently, during the recovery period, sympathetic burst frequency was higher in the hypoxia vs. the hypercapnia trial (166 +/- 21 vs. 104 +/- 15% of baseline in the last 5 min of a 20-min recovery period). We conclude that both hypoxia and hypercapnia cause substantial increases in sympathetic outflow to skeletal muscle. Hypercapnia-evoked sympathetic activation is short-lived, whereas hypoxia-induced sympathetic activation outlasts the chemical stimulus.

On the near-singularity of models for animal recovery data.

Certain probability models sometimes provide poor descriptions when fitted to data by maximum likelihood. We examine one such model for the survival of wild animals, which is fitted to two sets of data. When the model behaves poorly, its expected information matrix, evaluated at the maximum likelihood estimate of parameters, has a 'small' smallest eigenvalue. This is due to the fitted model being similar to a parameter-redundant submodel. In this case, model parameters that are precisely estimated have small coefficients in the eigenvector corresponding to the smallest eigenvalue. Approximate algebraic expressions are provided for the smallest eigenvalue. We discuss the general applicability of these results.