Air pollution modelling for birth cohorts: a time-space regression model

To investigate air pollution effects during pregnancy or in the first weeks of life, models are needed that capture both the spatial and temporal variability of air pollution exposures.; We developed a time-space exposure model for ambient NO2 concentrations in Bern, Switzerland. We used NO2 data from passive monitoring conducted between 1998 and 2009: 101 rural sites (24,499 biweekly measurements) and 45 urban sites (4350 monthly measurements). We evaluated spatial predictors (land use; roads; traffic; population; annual NO2 from a dispersion model) and temporal predictors (meteorological conditions; NO2 from continuous monitoring station). Separate rural and urban models were developed by multivariable regression techniques. We performed ten-fold internal cross-validation, and an external validation using 57 NO2 passive measurements obtained at study participant's homes.; Traffic related explanatory variables and fixed site NO2 measurements were the most relevant predictors in both models. The coefficient of determination (R(2)) for the log transformed models were 0.63 (rural) and 0.54 (urban); cross-validation R(2)s were unchanged indicating robust coefficient estimates. External validation showed R(2)s of 0.54 (rural) and 0.67 (urban).; This approach is suitable for air pollution exposure prediction in epidemiologic research with time-vulnerable health effects such as those occurring during pregnancy or in the first weeks of life

Reference Ability Neural Network‐selective functional connectivity across the lifespan

Previous studies have demonstrated that four latent variables, or reference abilities (RAs), can account for the majority of age‐related changes in cognition: these being episodic memory, fluid reasoning, speed of processing, and vocabulary. In the current study, we focused on RA‐selective functional connectivity patterns that vary with both age and behavior. We analyzed fMRI data from 287 community‐dwelling adults (20–80 years) on a battery of tests relating to the four RAs (three tests per RA = 12 tests). Functional connectivity values were calculated between a pre‐defined set of 264 ROIs (nodes). Across all participants, we (a) identified connections (edges) that correlated with an RA‐specific indicator variable and, indexing only these edges; (b) performed linear regression analysis per edge, regressing indicator correlations (Model 1) and connectivity values (Model 2) on Age, Behavioral Performance, and the Interaction term; and (c) took the conjunction of significant edges between models. Results revealed a different subset of edges for each RA whose connectivity strength and domain‐selectivity varied with age and behavior. Strikingly, the fluid reasoning RA was particularly vulnerable to the effects of age and displayed the most extensive connectivity and selectivity “footprint” for behavior. These findings indicate that different functional networks are recruited across RA, with fluid reasoning displaying a special status among them

Long-Range Correlations in Rectal Temperature Fluctuations of Healthy Infants during Maturation

BACKGROUND. Control of breathing, heart rate, and body temperature are interdependent in infants, where instabilities in thermoregulation can contribute to apneas or even life-threatening events. Identifying abnormalities in thermoregulation is particularly important in the first 6 months of life, where autonomic regulation undergoes critical development. Fluctuations in body temperature have been shown to be sensitive to maturational stage as well as system failure in critically ill patients. We thus aimed to investigate the existence of fractal-like long-range correlations, indicative of temperature control, in night time rectal temperature (Trec) patterns in maturing infants. METHODOLOGY/PRINCIPAL FINDINGS. We measured Trec fluctuations in infants every 4 weeks from 4 to 20 weeks of age and before and after immunization. Long-range correlations in the temperature series were quantified by the correlation exponent, a using detrended fluctuation analysis. The effects of maturation, room temperature, and immunization on the strength of correlation were investigated. We found that Trec fluctuations exhibit fractal long-range correlations with a mean (SD) a of 1.51 (0.11), indicating that Trec is regulated in a highly correlated and hence deterministic manner. A significant increase in a with age from 1.42 (0.07) at 4 weeks to 1.58 (0.04) at 20 weeks reflects a change in long-range correlation behavior with maturation towards a smoother and more deterministic temperature regulation, potentially due to the decrease in surface area to body weight ratio in the maturing infant. a was not associated with mean room temperature or influenced by immunization CONCLUSIONS. This study shows that the quantification of long-range correlations using a derived from detrended fluctuation analysis is an observer-independent tool which can distinguish developmental stages of night time Trec pattern in young infants, reflective of maturation of the autonomic system. Detrended fluctuation analysis may prove useful for characterizing thermoregulation in premature and other infants at risk for life-threatening events.British Society of the Protection of Infants Life; Swiss National Science Foundation (32-68025.02); ERS Long-Term Research Fellowship; National Science Foundation (BES 0114538); Swiss National Science Foundation (3200-B0-112099); Swiss Federal Office of Public Health (Anti-Tobacco Fund

Tidal Volume Single Breath Washout of Two Tracer Gases - A Practical and Promising Lung Function Test

Small airway disease frequently occurs in chronic lung diseases and may cause ventilation inhomogeneity (VI), which can be assessed by washout tests of inert tracer gas. Using two tracer gases with unequal molar mass (MM) and diffusivity increases specificity for VI in different lung zones. Currently washout tests are underutilised due to the time and effort required for measurements. The aim of this study was to develop and validate a simple technique for a new tidal single breath washout test (SBW) of sulfur hexafluoride (SF(6)) and helium (He) using an ultrasonic flowmeter (USFM)

Fractals for physicians

There is increasing interest in the study of fractals in medicine. In this review, we provide an overview of fractals, of techniques available to describe fractals in physiological data, and we propose some reasons why a physician might benefit from an understanding of fractals and fractal analysis, with an emphasis on paediatric respiratory medicine where possible. Among these reasons are the ubiquity of fractal organisation in nature and in the body, and how changes in this organisation over the lifespan provide insight into development and senescence. Fractal properties have also been shown to be altered in disease and even to predict the risk of worsening of disease. Finally, implications of a fractal organisation include robustness to errors during development, ability to adapt to surroundings, and the restoration of such organisation as targets for intervention and treatment

How can we measure the impact of pollutants on respiratory function in very young children? Methodological aspects

There is increasing evidence that air pollution particularly affects infants and small preschool children. However, detecting air pollution effects on lung function in small children is technically difficult and requires non-invasive methods that can assess lung function and inflammatory markers in larger cohorts. This review discusses the principles, usefulness and shortcomings of various lung function techniques used to detect pollution effects in small children. The majority of these techniques have been used to detect effects of the dominant indoor pollutant, tobacco exposure. However there is increasing evidence that non-invasive lung function techniques can also detect the effects of outdoor air pollution

Neural‐cognitive changes across the lifespan: Evidence from reference ability neural network (RANN) Neuroimaging/Normal brain aging

Background: Cognitive functions and their underlying neural substrates change across the lifespan (for a review, see Grady et al., 2012). In an attempt to capture these changes, most prior work utilizing a cross‐sectional approach have investigated age‐group differences in behavioral performance or neural activations related to particular functions. In the present study, we aimed to quantify neural changes in the brain associated with four principal cognitive domains by considering age as a continuous factor and linking regions displaying the greatest change in each domain with behavioral performance. Method: We collected behavioral and fMRI data from 240 cognitively‐healthy community‐dwelling adults between the ages of 21 and 80 on a battery of tests relating to the four domains or “reference abilities” (i.e., Episodic Memory, Fluid Reasoning, Processing Speed, Vocabulary; see Stern et al., 2014). We applied a Gaussian kernel, centered on each year of life in our sample, in order to generate weights that would allow us to construct a brain map for each target age, derived from the weighted activations across all participants (Ericsson et al., 2008). Subsequent subtraction of these maps allowed us to quantify the age‐related differences, ∆=T(age) ‐ T(age+1), in each domain. Result: Results indicated significant differences between successive ages around 40 years of age in two of the four domains: Fluid Reasoning and Processing Speed. Furthermore, for each domain, we selected those voxels for which change was the greatest and performed correlations between voxel activations and behavioral performance. For Episodic Memory, we observed significant positive correlations between behavior and activation namely in the bilateral rolandic operculum, thalamus, right postcentral gyrus, and left supramarginal gyrus, whereas for Processing Speed, we observed significant negative correlations largely in the supplementary motor area, left postcentral gyrus, right precentral gyrus, and cerebellum crus VI. Conclusion: These findings emphasize the utility of analyzing lifespan changes along a continuum and reveal significant differences, suggesting a significant peak change, that is similar across domains

A new double-tracer gas single-breath washout to assess early cystic fibrosis lung disease

In cystic fibrosis (CF), tests for ventilation inhomogeneity are sensitive but not established for clinical routine. We assessed feasibility of a new double-tracer gas single-breath washout (SBW) in school-aged children with CF and control subjects, and compared SBW between groups and with multiple-breath nitrogen washout (MBNW). Three SBW and MBNW were performed in 118 children (66 with CF) using a side-stream ultrasonic flowmeter setup. The double-tracer gas containing 5% sulfur hexafluoride and 26.3% helium was applied during one tidal breath. Outcomes were SBW phase III slope (SIII(DTG)), MBNW-derived lung clearance index (LCI), and indices of acinar (S(acin)) and conductive (S(cond)) ventilation inhomogeneity. SBW took significantly less time to perform than MBNW. SBW and MBNW were feasible in 109 (92.4%) and 98 (83.0%) children, respectively. SIII(DTG) differed between children with CF and controls, mean±sd was -456.7±492.8 and -88.4±129.1 mg·mol·L(-1), respectively. Abnormal SIII(DTG) was present in 36 (59%) children with CF. SIII(DTG) was associated with LCI (r= -0.58) and S(acin) (r= -0.58), but not with S(cond). In CF, steeply sloping SIII(DTG) potentially reflects ventilation inhomogeneity near the acinus entrance. This tidal SBW is a promising test to assess ventilation inhomogeneity in an easy and fast way