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Fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGL) catalyse the hydrolysis of the endocannabinoids anandamide and 2-arachidonoyl glycerol. We investigated their ultrastructural distribution in brain areas where the localization and effects of cannabinoid receptor activation are known. In the hippocampus, FAAH was present in somata and dendrites of principal cells, but not in interneurons. It was located mostly on the membrane surface of intracellular organelles known to store Ca(2+) (e.g. mitochondria, smooth endoplasmic reticulum), less frequently on the somatic or dendritic plasma membrane. MGL immunoreactivity was found in axon terminals of granule cells, CA3 pyramidal cells and some interneurons. In the cerebellum, Purkinje cells and their dendrites are intensively immunoreactive for FAAH, together with a sparse axon plexus at the border of the Purkinje cell/granule cell layers. Immunostaining for MGL was complementary, the axons in the molecular layer were intensively labelled leaving the Purkinje cell dendrites blank. FAAH distribution in the amygdala was similar to that of the CB(1) cannabinoid receptor: evident signal in neuronal somata and proximal dendrites in the basolateral nucleus, and hardly any labelling in the central nucleus. MGL staining was restricted to axons in the neuropil, with similar relative signal intensities seen for FAAH in different nuclei. Thus, FAAH is primarily a postsynaptic enzyme, whereas MGL is presynaptic. FAAH is associated with membranes of cytoplasmic organelles. The differential compartmentalization of the two enzymes suggests that anandamide and 2-AG signalling may subserve functional roles that are spatially segregated at least at the stage of metabolism.

The endogenous cannabinoids (endocannabinoids) are lipid molecules that may mediate retrograde signaling at central synapses and other forms of short-range neuronal communication. The monoglyceride 2-arachidonoylglycerol (2-AG) meets several criteria of an endocannabinoid substance: (i) it activates cannabinoid receptors; (ii) it is produced by neurons in an activity-dependent manner; and (iii) it is rapidly eliminated. 2-AG inactivation is only partially understood, but it may occur by transport into cells and enzymatic hydrolysis. Here we tested the hypothesis that monoglyceride lipase (MGL), a serine hydrolase that converts monoglycerides to fatty acid and glycerol, participates in 2-AG inactivation. We cloned MGL by homology from a rat brain cDNA library. Its cDNA sequence encoded for a 303-aa protein with a calculated molecular weight of 33,367 daltons. Northern blot and in situ hybridization analyses revealed that MGL mRNA is heterogeneously expressed in the rat brain, with highest levels in regions where CB(1) cannabinoid receptors are also present (hippocampus, cortex, anterior thalamus, and cerebellum). Immunohistochemical studies in the hippocampus showed that MGL distribution has striking laminar specificity, suggesting a presynaptic localization of the enzyme. Adenovirus-mediated transfer of MGL cDNA into rat cortical neurons increased MGL expression and attenuated N-methyl-D-aspartate/carbachol-induced 2-AG accumulation in these cells. No such effect was observed on the accumulation of anandamide, another endocannabinoid lipid. The results suggest that hydrolysis by means of MGL is a primary mechanism for 2-AG inactivation in intact neurons.

Stochastic algorithms are well-known for their performance in the era of big data. In this article, we study nonsmooth stochastic Difference-of-Convex functions (DC) programs-the major class of nonconvex stochastic optimization, which have a variety of applications in divers domains, in particular, machine learning. We propose new online stochastic algorithms based on the state-of-the-art DC Algorithm (DCA)-a powerful approach in nonconvex programming framework, in the online context of streaming data continuously generated by some (unknown) source distribution. The new schemes use the stochastic approximations (SAs) principle: deterministic quantities of the standard DCA are replaced by their noisy estimators constructed using newly arriving samples. The convergence analysis of the proposed algorithms is studied intensively with the help of tools from modern convex analysis and martingale theory. Finally, we study several aspects of the proposed algorithms on an important problem in machine learning: the expected problem in principal component analysis (PCA).

As reference genome assemblies are updated there is a need to convert epigenome sequence data from older genome assemblies to newer versions, to facilitate data integration and visualization on the same coordinate system. Conversion can be done by re-alignment of the original sequence data to the new assembly or by converting the coordinates of the data between assemblies using a mapping file, an approach referred to as 'liftover'. Compared to re-alignment approaches, liftover is a more rapid and cost-effective solution. Here, we benchmark six liftover tools commonly used for conversion between genome assemblies by coordinates, including UCSC liftOver , rtracklayer::liftOver , CrossMap , NCBI Remap , flo  and segment_liftover to determine how they performed for whole genome bisulphite sequencing (WGBS) and ChIP-seq data. Our results show high correlation between the six tools for conversion of 43 WGBS paired samples. For the chromatin sequencing data we found from interval conversion of 366 ChIP-Seq datasets, segment_liftover generates more reliable results than USCS liftOver . However, we found some regions do not always remain the same after liftover. To further increase the accuracy of liftover and avoid misleading results, we developed a three-step guideline that removes aberrant regions to ensure more robust genome conversion between reference assemblies., (© The Author(s) 2019. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)

This article describes the synthesis and characterization of tin-doped indium oxide (ITO) and platinum nanoparticles deposited on ITO. For different calcination temperatures, the tin-doped indium oxide nanoparticles (ITO NPs) were synthesized successfully by a nonaqueous sol-gel method with indium acetylacetonate and tin bis(acetylacetonate) dichloride in oleylamine as the precursors. The ITO sample that calcinated at 500 °C exhibited a spherical morphology with a narrow range of the particle size distribution (15-20 nm). Moreover, the electrical conductivity of the sample (1.242 S/cm) was higher than many different non-carbon supports. In addition, 20% platinum nanoparticles (Pt NPs) were also deposited uniformly on the ITO supports via chemical reduction process using NaBH4 as the reducing agent. The size of Pt NPs was about 5 nm and the crystalline structure of ITO supports remained unchanged.

In this paper, Fe@SiO2 nanoparticles (α-Fe nanoparticles coated with SiO2 shell) were synthesized at room temperature using the modified Stöber method combined with potassium borohydride (KBH4) reduction process. The present study depicts the facile synthesis of Fe@SiO2 without the presence of surfactants and stabilizers. In this experiment, KBH4 acted both as a reducing agent for iron salt and a catalyst for hydrolysis and polycondensation of tetraethylorthosilicate (TEOS). The Fe@SiO2 nanoparticles were characterized using X-ray diffraction method, specific surface area (BET) technique, transmission electron microscope (TEM), and vibrating sample magnetometer (VSM). The optimal mass ratio of Fe in the form of anhydrous ferric chloride (FeCl3) and SiO2) in the form of TEOS was 4:1. α-Fe-Fe nanoparticles (size of about 45 nm) were coated with approximately 10 nm thick SiO2 shells. Moreover, Fe/SiO2 (Fe0 nanoparticles supported by silica nanoparticles) was synthesized to compare the results. Due to the silica shells, Fe cores cannot be oxidized when dipped in the concentrated sulfuric acid, and hence, the removal of Cr(VI) was not weakened in the acidic environment.

This letter proposes a novel approach using the [Formula: see text]-norm regularization for the sparse covariance matrix estimation (SCME) problem. The objective function of SCME problem is composed of a nonconvex part and the [Formula: see text] term, which is discontinuous and difficult to tackle. Appropriate DC (difference of convex functions) approximations of [Formula: see text]-norm are used that result in approximation SCME problems that are still nonconvex. DC programming and DCA (DC algorithm), powerful tools in nonconvex programming framework, are investigated. Two DC formulations are proposed and corresponding DCA schemes developed. Two applications of the SCME problem that are considered are classification via sparse quadratic discriminant analysis and portfolio optimization. A careful empirical experiment is performed through simulated and real data sets to study the performance of the proposed algorithms. Numerical results showed their efficiency and their superiority compared with seven state-of-the-art methods.

The ionization and fragmentation processes for pentachlorobenzene were examined using a femtosecond laser emitting at 400, 800, and 1200 nm. A molecular ion was clearly observed in the mass spectrum, since the molecule can be directly ionized from the singlet electronic exited state before relaxation to triplet levels, because the pulse width of the laser is shorter than the lifetime of the excited state. Fragmentation was minimal at 1200 nm, in contrast to ionization at 800 and 400 nm. Indeed, a doubly-charged molecular ion was prominent at 800 nm, owing to the absorption band of the singly-charged molecular ion at this wavelength. Fragmentation was further enhanced at 400 nm, which can be explained by the dissociation of the doubly-charged molecular ion having a larger absorption band at 400 nm. Fragmentation was strongly affected by the absorption character of the ionic species, i.e., singly- and doubly-charged molecular ions, appeared in the process of multiphoton ionization.

In this letter, we consider the nonnegative matrix factorization (NMF) problem and several NMF variants. Two approaches based on DC (difference of convex functions) programming and DCA (DC algorithm) are developed. The first approach follows the alternating framework that requires solving, at each iteration, two nonnegativity-constrained least squares subproblems for which DCA-based schemes are investigated. The convergence property of the proposed algorithm is carefully studied. We show that with suitable DC decompositions, our algorithm generates most of the standard methods for the NMF problem. The second approach directly applies DCA on the whole NMF problem. Two algorithms-one computing all variables and one deploying a variable selection strategy-are proposed. The proposed methods are then adapted to solve various NMF variants, including the nonnegative factorization, the smooth regularization NMF, the sparse regularization NMF, the multilayer NMF, the convex/convex-hull NMF, and the symmetric NMF. We also show that our algorithms include several existing methods for these NMF variants as special versions. The efficiency of the proposed approaches is empirically demonstrated on both real-world and synthetic data sets. It turns out that our algorithms compete favorably with five state-of-the-art alternating nonnegative least squares algorithms.

Introduction: Upper extremity deep vein thrombosis is an increasingly important clinical finding with significant morbidity and mortality. The condition may be under-diagnosed in trauma and surgery settings., Presentation of Case: We present a case of upper extremity thrombosis with venous congestive symptoms secondary to the use of an operative tourniquet. A literature review and discussion of the causes of upper extremity deep vein thrombosis and the pathophysiological disturbances seen with tourniquet use are presented., Discussion: Upper extremity deep venous thrombosis is uncommon. In this case the likely cause was operative tourniquet use., Conclusion: Operative tourniquet may be a risk factor in upper extremity deep vein thrombosis., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Automatic discovery of community structures in complex networks is a fundamental task in many disciplines, including physics, biology, and the social sciences. The most used criterion for characterizing the existence of a community structure in a network is modularity, a quantitative measure proposed by Newman and Girvan (2004). The discovery community can be formulated as the so-called modularity maximization problem that consists of finding a partition of nodes of a network with the highest modularity. In this letter, we propose a fast and scalable algorithm called DCAM, based on DC (difference of convex function) programming and DCA (DC algorithms), an innovative approach in nonconvex programming framework for solving the modularity maximization problem. The special structure of the problem considered here has been well exploited to get an inexpensive DCA scheme that requires only a matrix-vector product at each iteration. Starting with a very large number of communities, DCAM furnishes, as output results, an optimal partition together with the optimal number of communities [Formula: see text]; that is, the number of communities is discovered automatically during DCAM's iterations. Numerical experiments are performed on a variety of real-world network data sets with up to 4,194,304 nodes and 30,359,198 edges. The comparative results with height reference algorithms show that the proposed approach outperforms them not only on quality and rapidity but also on scalability. Moreover, it realizes a very good trade-off between the quality of solutions and the run time.

Background: Excessive gingival display, or a "gummy smile," is defined as 2 mm or more of gingival exposure upon smiling. Such excessive gingival exposure can be aesthetically unappealing to patients. One factor that contributes to a gummy smile is hyperfunctional lip elevator muscles., Objectives: The authors evaluate onabotulinumtoxinA as a safe and minimally invasive treatment for a gummy smile., Methods: In this prospective study, 14 patients (13 women, 1 man) underwent pretreatment photographs and measurements, followed by bilateral injection of onabotulinumtoxinA into their lip elevator muscles. All patients selected for the study had more than 2mm of gingival show and were classified as having a "cuspid smile," where action of all elevator muscles raised the upper lip- like a window shade-to expose the upper teeth and gingival scaffold; these patients were thought to have a better chance for a more superior result. Repeat measurements and photographs were collected at 2 weeks and 3 months. Patient-reported outcomes were collected at 2 weeks, and data were compared to determine the correlative relationship., Results: An average of 5 units (range, 4-6 U) of onabotulinumtoxinA were injected into 3 sites bilaterally. The average preinjection gingival show over the central incisors and canines were 4.89 mm and 4.25 mm, respectively. Postinjection gingival show decreased to an average of 0.75 mm (85% improvement) and 0.74 mm (83% improvement) over the central incisors and canines, respectively. Average follow-up time was 12.6 days. One patient felt the resulting smile was unattractive and opted not to undergo repeat injections, while all other study participants experienced no negative effects and wished to undergo repeat treatment., Conclusions: As treatment for a "gummy smile," onabotulinumtoxinA provides an effective, minimally invasive, and safe therapy. This treatment option can lead to significant improvement in smile aesthetics with high patient satisfaction., Level of Evidence: 3.

Objective. The correlation between obesity and deficient wound healing has long been established. This review examines the current literature on the mechanisms involved in obesity-related perioperative morbidity. Methods. A literature search was performed using Medline, PubMed, Cochrane Library, and Internet searches. Keywords used include obesity, wound healing, adipose healing, and bariatric and surgical complications. Results. Substantial evidence exists demonstrating that obesity is associated with a number of postoperative complications. Specifically in relation to wound healing, explanations include inherent anatomic features of adipose tissue, vascular insufficiencies, cellular and composition modifications, oxidative stress, alterations in immune mediators, and nutritional deficiencies. Most recently, advances made in the field of gene array have allowed researchers to determine a few plausible alterations and deficiencies in obese individuals that contribute to their increased risk of morbidity and mortality, especially wound complications. Conclusion. While the literature discusses how obesity may negatively affect health on various of medical fronts, there is yet to be a comprehensive study detailing all the mechanisms involved in obesity-related morbidities in their entirety. Improved knowledge and understanding of obesity-induced physiological, cellular, molecular, and chemical changes will facilitate better assessments of surgical risks and outcomes and create efficient treatment protocols for improved patient care of the obese patient population.

We investigate difference of convex functions (DC) programming and the DC algorithm (DCA) to solve the block clustering problem in the continuous framework, which traditionally requires solving a hard combinatorial optimization problem. DC reformulation techniques and exact penalty in DC programming are developed to build an appropriate equivalent DC program of the block clustering problem. They lead to an elegant and explicit DCA scheme for the resulting DC program. Computational experiments show the robustness and efficiency of the proposed algorithm and its superiority over standard algorithms such as two-mode K-means, two-mode fuzzy clustering, and block classification EM.

Background: Vietnam has achieved considerable success in economic development, poverty reduction, and health over a relatively short period of time. However, there is concern that inequalities in health outcomes and intervention coverage are widening. This study explores if inequalities in reproductive, maternal, newborn and child health and nutrition changed over time in Vietnam in 1997-2006, and if inequalities were different depending on the type of stratifying variable used to measure inequalities and on the type of outcome studied., Methods: Using data from four nationally representative household surveys conducted in 1997-2006, we study inequalities in reproductive, maternal, newborn and child health and nutrition outcomes and intervention coverage by computing concentration indices by living standards, maternal education, ethnicity, region, urban/rural residence, and sex of child., Results: Inequalities in maternal, newborn and child health persisted in 1997-2006. Inequalities were largest by living standards, but not trivial by the other stratifying variables. Inequalities in health outcomes generally increased over time, while inequalities in intervention coverage generally declined. The most equitably distributed interventions were family planning, exclusive breastfeeding, and immunizations. The most inequitably distributed interventions were those requiring multiple service contacts, such as four or more antenatal care visits, and those requiring significant support from the health system, such as skilled birth attendance., Conclusions: Three main policy implications emerge. First, persistent inequalities suggest the need to address financial and other access barriers, for example by subsidizing health care for the poor and ethnic minorities and by support from other sectors, for example in strengthening transportation networks. This should be complemented by careful monitoring and evaluation of current program design and implementation to ensure effective and efficient use of resources. Second, greater inequalities for interventions that require multiple service contacts imply that inequalities could be reduced by strengthening information and service provision by community and village health workers to promote and sustain timely care-seeking. Finally, larger inequalities for interventions that require a fully functioning health system suggest that investments in health facilities and human resources, particularly in areas that are disproportionately inhabited by the poor and ethnic minorities, may contribute to reducing inequalities.

The endogenous cannabinoid 2-arachidonoylglycerol (2-AG) is produced by neurons and other cells in a stimulus-dependent manner and undergoes rapid biological inactivation through transport into cells and catalytic hydrolysis. The enzymatic pathways responsible for 2-AG degradation are only partially understood. We have shown previously that overexpression of monoacylglycerol lipase (MGL), a cytosolic serine hydrolase that cleaves 1- and 2-monoacylglycerols to fatty acid and glycerol, reduces stimulus-dependent 2-AG accumulation in primary cultures of rat brain neurons. We report here that RNA interference-mediated silencing of MGL expression greatly enhances 2-AG accumulation in HeLa cells. After stimulation with the calcium ionophore ionomycin, 2-AG levels in MGL-silenced cells were comparable with those found in cells in which 2-AG degradation had been blocked using methyl arachidonyl fluorophosphonate, a nonselective inhibitor of 2-AG hydrolysis. The results indicate that MGL plays an important role in the degradation of endogenous 2-AG in intact HeLa cells. Furthermore, immunodepletion experiments show that MGL accounts for at least 50% of the total 2-AG-hydrolyzing activity in soluble fractions of rat brain, suggesting that this enzyme also contributes to 2-AG deactivation in the central nervous system.

To investigate the interindividual differences in respiratory sinus arrhythmia (RSA), recordings of ventilation and electrocardiogram were obtained from 12 healthy subjects for five imposed breathing periods (T(TOT)) surrounding each individual's spontaneous breathing period. In addition to the spectral analysis of the R-R interval signal at each breathing period, RSA characteristics were quantified by using a breath-by-breath analysis where a sinusoid was fitted to the changes in instantaneous heart rate in each breath. The amplitude and phase (or delay = phase x T(TOT)) of this sinusoid were taken as the RSA characteristics for each breath. It was found that for each subject the RSA amplitude-T(TOT) relationship was linear, whereas the delay-T(TOT) relationship was parabolic. However, the parameters of these relationships differed between individuals. Linear correlation between the slopes of RSA amplitude versus T(TOT) regression lines and 1) mean breathing period and 2) mean R-R interval during spontaneous breathing were calculated. Only the correlation coefficient with breathing period was significantly different from zero, indicating that the longer the spontaneous breathing period the lesser the increase in RSA amplitude with increasing breathing period. Similarly, only the correlation coefficient between the curvature of the RSA delay-T(TOT) parabola and mean breathing period was significantly different from zero; the longer the spontaneous breathing period the larger the curvature of RSA delay. These results suggest that the changes in RSA characteristics induced by changing the breathing period may be explained partly by the spontaneous breathing period of each individual. Furthermore, a transfer function analysis performed on these data suggested interindividual differences in the autonomic modulation of the heart rate.

Studies of heart rate variability (HRV) have so far produced contradictory evidence to support the common belief that endurance training enhances cardiac parasympathetic tone. This may be related to the fact that most studies failed to specifically isolate the vagally mediated influence of respiration. This study used a cross-sectional comparison of endurance athletes (n=20; ATHL) exhibiting resting bradycardia and age-matched nonathletes (n=12; CRTL) to indirectly assess training effects on amplitude and timing characteristics of respiratory sinus arrhythmia (RSA). Continuous electrocardiogram (ECG) and ventilatory flows were recorded during spontaneous breathing (SP), as well as during breathing at four cycles less than (M4) or more (P4) than SP, to also examine potential repercussions of training on the sensitivity of the cardiac vagal responses to breathing. A fast Fourier transform procedure was used to quantify the standard spectral high-frequency (HF) and low-frequency (LF) components and a respiratory-centered frequency (RCF) component of HRV. RSA was assessed using a breath-by-breath quantification of the amplitude and timing of the maximum change in instantaneous heart rate. Under baseline SP conditions, heart rate was lower in ATHL (62.6+/-6.5 vs. 75.2+/-9 beats/min; p<0.05) while blood pressure (BP), breath cycle duration, tidal volume, and ventilatory drive were similar in both groups. HRV total spectral power density, LF, HF, or RCF was not different between groups at either the SP, M4, or P4 conditions. Changes in total breath duration similarly affected RSA amplitude in all groups, while HR and BP remained unchanged from SP. RSA phase was not affected by training status or by changes in total breath duration. RSA amplitude was negatively related to breathing frequency in all groups (p<0.05), while the mean slope of the relationship (sensitivity) was not different between groups. In as much as RSA is an adequate marker of cardiac vagal efferent activity, these results add support to a contribution of a decrease in intrinsic heart rate to explain training-induced bradycardia.

Febrile (fever-induced) seizures are the most common form of childhood seizures, affecting 3%-5% of infants and young children. Here we show that the activity-dependent, retrograde inhibition of GABA release by endogenous cannabinoids is persistently enhanced in the rat hippocampus following a single episode of experimental prolonged febrile seizures during early postnatal development. The potentiation of endocannabinoid signaling results from an increase in the number of presynaptic cannabinoid type 1 receptors associated with cholecystokinin-containing perisomatic inhibitory inputs, without an effect on the endocannabinoid-mediated inhibition of glutamate release. These results demonstrate a selective, long-term increase in the gain of endocannabinoid-mediated retrograde signaling at GABAergic synapses in a model of a human neurological disease.

2-Arachidonoylglycerol (2-AG) is a naturally occurring monoglyceride that activates cannabinoid receptors and meets several key requisites of an endogenous cannabinoid substance. It is present in the brain (where its levels are 170-folds higher than those of anandamide), is produced by neurons in an activity- and calcium-dependent manner, and is rapidly eliminated. The mechanism of 2-AG inactivation is not completely understood, but is thought to involve carrier-mediated transport into cells followed by enzymatic hydrolysis. We examined the possible role of the serine hydrolase, monoglyceride lipase (MGL), in brain 2-AG inactivation. We identified by homology screening a cDNA sequence encoding for a 303-amino acid protein, which conferred MGL activity upon transfection to COS-7 cells. Northern blot and in situ hybridization analyses revealed that MGL mRNA is unevenly present in the rat brain, with highest levels in regions where CB1 cannabinoid receptors are also expressed (hippocampus, cortex, anterior thalamus and cerebellum). Immunohistochemical studies in the hippocampus showed that MGL distribution has striking laminar specificity, suggesting a presynaptic localization of the enzyme. Adenovirus-mediated transfer of MGL cDNA into rat cortical neurons increased the degradation of endogenously produced 2-AG in these cells, whereas no such effect was observed on anandamide degradation. These results indicate that hydrolysis via MGL may be a primary route of 2-AG inactivation in intact neuronal cells.

The addition to the respiratory system of a resistive load results in breathing pattern changes and in negative intrathoracic pressure increases. The aim of this study was to use resistive load breathing as a stimulus to the cardiorespiratory interaction and to examine the extent of the changes in heart rate variability (HRV) and respiratory sinus arrhythmia (RSA) in relation to the breathing pattern changes. HRV and RSA were studied in seven healthy subjects where four resistive loads were applied in a random order during the breath and 8-min recording made in each condition. The HRV spectral power components were computed from the R-R interval sequences, and the RSA amplitude and phase were computed from the sinusoid fitting the instantaneous heart rate within each breath. Adding resistive loads resulted in 1) increasing respiratory period, 2) unchanging heart rate, and 3) increasing HRV and changing RSA characteristics. HRV and RSA characteristics are linearly correlated to the respiratory period. These modifications appear to be linked to load-induced changes in the respiratory period in each individual, because HRV and RSA characteristics are similar at a respiratory period obtained either by loading or by imposed frequency breathing. The present results are discussed with regard to the importance of the breathing cycle duration in these cardiorespiratory interactions, suggesting that these interactions may depend on the time necessary for activation and dissipation of neurotransmitters involved in RSA.

A statistical method with the advantages of 1) enabling graphical representation of within-respiratory cycle heart rate variations, 2) detecting the presence of respiratory sinus arrhythmia (RSA) in a moving window, and 3) providing breath-by-breath RSA amplitude and phase obtained from the fitting of a sinusoid to the instantaneous relative heart rate is presented.

In order to determine changes in breathing patterns brought about by resistive loading, ventilation was recorded in 11 healthy subjects with four linear resistances (3.57, 5.75, 8.76 and 13.13 cmH2O L(-1) sec) added in a random order throughout the entire breath. At steady state, a breath-by-breath analysis of airflow was used to quantify the pattern of breathing in terms of respiratory variables: TI, TE, Tt, VT, VT/TI, TI/Tt, and by taking TI, TE, VT all together (TRIAD) and also the shape of the entire airflow profile quantified by harmonic analysis (ASTER). Group analysis using ANOVA showed significant changes in all variables. There were increasing changes with increasing loads in all variables, the smallest changes being in TI/Tt. Within to between-individual comparisons between two loads showed that only TI/Tt and the ASTER were more similar within than between-individuals for all comparisons. It was concluded that at steady state mechanisms of load compensation come into play inducing changes in the pattern of breathing proportional to the loads while maintaining some of the individual characteristics.

To better understand behavioural and genetic influences upon breathing, the breathing patterns of 8 pairs of monozygous (MZ) twins were measured under 4 behavioural conditions; relaxed without standardisation; eyes closed; eyes open; and reading. Breathing was quantified by inspiratory and expiratory durations (TI, TE), tidal volume (VT) and derived variables. Airflow shape was normalised and quantified using 8 dimensions. Reading caused breathing to increase by > 500 ml/min compared to the other four conditions. Differences in breathing between combinations of two conditions were compared by testing whether the differences within an individual were smaller than the differences between random pairs of individuals from the same 16 subjects. For almost all respiratory variables, and whatever the behavioural condition, there were highly significant similarities within an individual (p < 0.00025 on 32/80 comparisons). Under each condition, the differences within MZ twin-pairs were compared to the differences within random-pairs from the same subject population. There were highly significant similarities within twin-pairs for the airflow shape across all conditions. However, TI, TE and VT failed to consistently show significant similarities within twin pairs. Hence, an individual's airflow shape appears to be a fundamental characteristic which is conserved when behavioural condition and level of ventilation changes. Further, MZ twins have similar airflow shapes--whatever the behavioural situation. Hence, behavioural influences upon airflow shape act upon monozygous twin pairs in similar ways, or such influences were negligible under the conditions of the present study.

Sixteen healthy adult subjects underwent two studies separated by 4-5 years to test whether their resting pattern of breathing was reproducible over time. From breath-by-breath analysis of airflow, measured with a pneumotachometer, the pattern of breathing was quantified in terms of individual respiratory variables; inspiratory time (TI), expiratory time (TE), total breath duration (TTOT), tidal volume (VT), VT/TI, TI/TTOT, and by taking TI, TE and VT all together (TRIAD). Also, the shape of the entire airflow profile was quantified by harmonic analysis (ASTER). A statistical analysis was designed to compare differences between the 1st and the 2nd recording within individuals with those differences observed between random pairs of recordings from the two studies in the same 16 individuals. It was found that all variables were significantly more similar within-individuals than between-individuals; this is best demonstrated when considering the ASTER and/or the TRIAD. It was concluded that the individuality of breathing pattern is maintained over a long period despite changes in smoking habit, weight, mild respiratory diseases, and other changes which occurred between the two studies in our subjects.