Local-global splitting for spatiotemporal-adaptive multiscale methods

We present a novel spatiotemporal-adaptive Multiscale Finite Volume (MsFV) method, which is based on the natural idea that the global coarse-scale problem has longer characteristic time than the local fine-scale problems. As a consequence, the global problem can be solved with larger time steps than the local problems. In contrast to the pressure-transport splitting usually employed in the standard MsFV approach, we propose to start directly with a local-global splitting that allows to locally retain the original degree of coupling. This is crucial for highly non-linear systems or in the presence of physical instabilities. To obtain an accurate and efficient algorithm, we devise new adaptive criteria for global update that are based on changes of coarse-scale quantities rather than on fine-scale quantities, as it is routinely done before in the adaptive MsFV method. By means of a complexity analysis we show that the adaptive approach gives a noticeable speed-up with respect to the standard MsFV algorithm. In particular, it is efficient in case of large upscaling factors, which is important for multiphysics problems. Based on the observation that local time stepping acts as a smoother, we devise a self-correcting algorithm which incorporates the information from previous times to improve the quality of the multiscale approximation. We present results of multiphase flow simulations both for Darcy-scale and multiphysics (hybrid) problems, in which a local pore-scale description is combined with a global Darcy-like description. The novel spatiotemporal-adaptive multiscale method based on the local-global splitting is not limited to porous media flow problems, but it can be extended to any system described by a set of conservation equations.

Respiratory muscle training enhances maximal minute ventilation and forced vital capacity in adolescent athletes.

Introduction. Respiratory difficulties in athletes are common, especially in adolescents, even in the absence of exercise-induced bronchoconstriction. Immaturity of the respiratory muscles coupling at high respiratory rates could be a potential mechanism. Whether respiratory muscle training (RMT) can positively influence it is yet unknown. Goal. We investigate the effects of RMT on ventilation and performance parameters in adolescent athletes and hypothesize that RMT will enhance respiratory capacity. Methods. 12 healthy subjects (8 male, 4 female, 17±0.5 years) from a sports/study high school class, competitively involved in various sports (minimum of 10 hours per week) underwent respiratory function testing, maximal minute ventilation (MMV) measurements and a maximal treadmill incremental test with VO2max and ventilatory thresholds (VT1 and VT2) determination. They then underwent one month of RMT (4 times/week) using a eucapnic hyperventilation device, with an incremental training program. The same tests were repeated after RMT. Results. Subjects completed 14.8 sessions of RMT, with an increase in total ventilation per session of 211±29% during training. Borg scale evaluation of the RMT session was unchanged or reduced in all subjects, despite an increase in total respiratory work. No changes (p>0.05) were observed pre/post RMT in VO2max (53.4±7.5 vs 51.6±7.7 ml/kg/min), VT2 (14.4±1.4 vs 14.0±1.1 km/h) or Speed max at end of test (16.1±1.7 vs 15.8±1.7 km/h). MVV increased by 9.2% (176.7±36.9 vs 192.9±32.6 l/min, p<0.001) and FVC by 3.3% (6.70±0.75 vs 4.85±0.76 litres, p<0.05). Subjective evaluation of respiratory sensations during exercise and daily living were also improved. Conclusions. RMT improves MMV and FVC in adolescent athletes, along with important subjective respiratory benefits, although no changes are seen in treadmill maximal performance tests and VO2max measurements. RMT can be easily performed in adolescent without side effects, with a potential for improvement in training capacity and overall well-being.

The AP-1 transcription factor c-Jun prevents stress-imposed maladaptive remodeling of the heart.

Systemic hypertension increases cardiac workload and subsequently induces signaling networks in heart that underlie myocyte growth (hypertrophic response) through expansion of sarcomeres with the aim to increase contractility. However, conditions of increased workload can induce both adaptive and maladaptive growth of heart muscle. Previous studies implicate two members of the AP-1 transcription factor family, junD and fra-1, in regulation of heart growth during hypertrophic response. In this study, we investigate the function of the AP-1 transcription factors, c-jun and c-fos, in heart growth. Using pressure overload-induced cardiac hypertrophy in mice and targeted deletion of Jun or Fos in cardiomyocytes, we show that c-jun is required for adaptive cardiac hypertrophy, while c-fos is dispensable in this context. c-jun promotes expression of sarcomere proteins and suppresses expression of extracellular matrix proteins. Capacity of cardiac muscle to contract depends on organization of principal thick and thin filaments, myosin and actin, within the sarcomere. In line with decreased expression of sarcomere-associated proteins, Jun-deficient cardiomyocytes present disarrangement of filaments in sarcomeres and actin cytoskeleton disorganization. Moreover, Jun-deficient hearts subjected to pressure overload display pronounced fibrosis and increased myocyte apoptosis finally resulting in dilated cardiomyopathy. In conclusion, c-jun but not c-fos is required to induce a transcriptional program aimed at adapting heart growth upon increased workload.

The Innovation and Imitation Dichotomy in Spanish firms: do absorptive capacity and the technological frontier matter?

This paper analyses whether a firm’s absorptive capacity and its distance from the technological frontier affect the choice between innovation and imitation in innovative Spanish firms. From an extensive survey of 5,575 firms during the 2004-2009 period, we found two significant results. With regard to the role of absorptive capacity, the empirical evidence shows that when innovative firms have difficulties in accessing external information and hire skilled workers, their innovative capacity is reduced. Meanwhile, with regard to distance from the technological frontier, the firms that reduce this gap manage to increase their innovative capacity at the expense of imitation. To summarise, when we studied firms’ absorptive capacity and their relative position to the technological frontier in tandem, we found that the two factors directly affected firms' ability to innovate or imitate.

Experimental peripheral arterial disease: new insights into muscle glucose uptake, macrophage, and T-cell polarization during early and late stages.

Peripheral arterial disease (PAD) is a common disease with increasing prevalence, presenting with impaired walking ability affecting patient's quality of life. PAD epidemiology is known, however, mechanisms underlying functional muscle impairment remain unclear. Using a mouse PAD model, aim of this study was to assess muscle adaptive responses during early (1 week) and late (5 weeks) disease stages. Unilateral hindlimb ischemia was induced in ApoE(-/-) mice by iliac artery ligation. Ischemic limb perfusion and oxygenation (Laser Doppler imaging, transcutaneous oxygen pressure assessments) significantly decreased during early and late stage compared to pre-ischemia, however, values were significantly higher during late versus early phase. Number of arterioles and arteriogenesis-linked gene expression increased at later stage. Walking ability, evaluated by forced and voluntary walking tests, remained significantly decreased both at early and late phase without any significant improvement. Muscle glucose uptake ([18F]fluorodeoxyglucose positron emission tomography) significantly increased during early ischemia decreasing at later stage. Gene expression analysis showed significant shift in muscle M1/M2 macrophages and Th1/Th2 T cells balance toward pro-inflammatory phenotype during early ischemia; later, inflammatory state returned to neutrality. Muscular M1/M2 shift inhibition by a statin prevented impaired walking ability in early ischemia. High-energy phosphate metabolism remained unchanged (31-Phosphorus magnetic resonance spectroscopy). Results show that rapid transient muscular inflammation contributes to impaired walking capacity while increased glucose uptake may be a compensatory mechanisms preserving immediate limb viability during early ischemia in a mouse PAD model. With time, increased ischemic limb perfusion and oxygenation assure muscle viability although not sufficiently to improve walking impairment. Subsequent decreased muscle glucose uptake may partly contribute to chronic walking impairment. Early inflammation inhibition and/or late muscle glucose impairment prevention are promising strategies for PAD management.

Innovation and absorptive capacity: What is the role of technological frontier?

This paper explores how absorptive capacity affects the innovative performance and productivity dynamics of Spanish firms. A firm’s efficiency levels are measured using two variables: the labour productivity and the Total Factor Productivity (TFP). The theoretical framework is based on the seminal contributions of Cohen and Levinthal (1989, 1990) regarding absorptive capacity; and the applied framework is based on the four-stage structural model proposed by Crépon, Duguet and Mairesse (1998) for setting the determinants of R&D, the effects of R&D activities on innovation outputs, and the impacts of innovation on firm productivity. The present study uses a twostage structural model. In the first stage, a probit estimation is used to investigate how the sources of R&D, the absorptive capacity and a vector of the firm’s individual features influence the firm’s likelihood of developing innovations in products or processes. In the second phase, a quantile regression is used to analyze the effect of R&D sources, absorptive capacity and firm characteristics on productivity. This method shows the elasticity of each exogenous variable on productivity according to the firms’ levels of efficiency, and thus allows us to distinguish between firms that are close to the technological frontier and those that are further away from it. We used extensive firm-level panel data from 5,575 firms for the 2004-2009 period. The results show that the internal absorptive capacity has a strong impact on the productivity of firms, whereas the role of external absorptive capacity differs according to nature of the each industry and according the distance of firms from the technological frontier. Key words: R&D sources, innovation strategies, absorptive capacity, technological distance, quantile regression.

The Innovation and Imitation Dichotomy in Spanish firms: do absorptive capacity and the technological frontier matter?

This paper analyses whether a firm’s absorptive capacity and its distance from the technological frontier affect the choice between innovation and imitation in innovative Spanish firms. From an extensive survey of 5,575 firms during the 2004-2009 period, we found two significant results. With regard to the role of absorptive capacity, the empirical evidence shows that when innovative firms have difficulties in accessing external information and hire skilled workers, their innovative capacity is reduced. Meanwhile, with regard to distance from the technological frontier, the firms that reduce this gap manage to increase their innovative capacity at the expense of imitation. To summarise, when we studied firms’ absorptive capacity and their relative position to the technological frontier in tandem, we found that the two factors directly affected firms' ability to innovate or imitate. Key words: R&D sources, innovation and imitation strategies, absorptive capacity, technological frontier, ordered probit.

Proliferation capacity and cytotoxic activity are mediated by functionally and phenotypically distinct virus-specific CD8 T cells defined by interleukin-7R{alpha} (CD127) and perforin expression.

Cytotoxicity and proliferation capacity are key functions of antiviral CD8 T cells. In the present study, we investigated a series of markers to define these functions in virus-specific CD8 T cells. We provide evidence that there is a lack of coexpression of perforin and CD127 in human CD8 T cells. CD127 expression on virus-specific CD8 T cells correlated positively with proliferation capacity and negatively with perforin expression and cytotoxicity. Influenza virus-, cytomegalovirus-, and Epstein-Barr virus/human immunodeficiency virus type 1-specific CD8 T cells were predominantly composed of CD127(+) perforin(-)/CD127(-) perforin(+), and CD127(-)/perforin(-) CD8 T cells, respectively. CD127(-)/perforin(-) and CD127(-)/perforin(+) cells expressed significantly more PD-1 and CD57, respectively. Consistently, intracellular cytokine (gamma interferon, tumor necrosis factor alpha, and interleukin-2 [IL-2]) responses combined to perforin detection confirmed that virus-specific CD8 T cells were mostly composed of either perforin(+)/IL-2(-) or perforin(-)/IL-2(+) cells. In addition, perforin expression and IL-2 secretion were negatively correlated in virus-specific CD8 T cells (P &lt; 0.01). As previously shown for perforin, changes in antigen exposure modulated also CD127 expression. Based on the above results, proliferating (CD127(+)/IL-2-secreting) and cytotoxic (perforin(+)) CD8 T cells were contained within phenotypically distinct T-cell populations at different stages of activation or differentiation and showed different levels of exhaustion and senescence. Furthermore, the composition of proliferating and cytotoxic CD8 T cells for a given antiviral CD8 T-cell population appeared to be influenced by antigen exposure. These results advance our understanding of the relationship between cytotoxicity, proliferation capacity, the levels of senescence and exhaustion, and antigen exposure of antiviral memory CD8 T cells.

Hybridisation and diversification in the adaptive radiation of clownfishes.

BackgroundThe importance of hybridisation during species diversification has long been debated among evolutionary biologists. It is increasingly recognised that hybridisation events occurred during the evolutionary history of numerous species, especially during the early stages of adaptive radiation. We study the effect of hybridisation on diversification in the clownfishes, a clade of coral reef fish that diversified through an adaptive radiation process. While two species of clownfish are likely to have been described from hybrid specimens, the occurrence and effect of hybridisation on the clade diversification is yet unknown.ResultsWe generate sequences of three mitochondrial genes to complete an existing dataset of nuclear sequences and document cytonuclear discordance at a node, which shows a drastic increase of diversification rate. Then, using a tree-based jack-knife method, we identify clownfish species likely stemming from hybridisation events. Finally, we use molecular cloning and identify the putative parental species of four clownfish specimens that display the morphological characteristics of hybrids.ConclusionsOur results show that consistently with the syngameon hypothesis, hybridisation events are linked with a burst of diversification in the clownfishes. Moreover, several recently diverged clownfish lineages likely originated through hybridisation, which indicates that diversification, catalysed by hybridisation events, may still be happening.

Long-term health-related quality of life and walking capacity of lung recipients with and without bronchiolitis obliterans syndrome.

BACKGROUND: Outcome after lung transplantation (LTx) is affected by the onset of bronchiolitis obliterans syndrome (BOS) and lung function decline. Reduced health-related quality of life (HRQL) and physical mobility have been shown in patients developing BOS, but the impact on the capacity to walk is unknown. We aimed to compare the long-term HRQL and 6-minute walk test (6MWT) between lung recipients affected or not by BOS Grade > or =2. METHODS: Fifty-eight patients were prospectively followed for 5.6 +/- 2.9 years after LTx. Assessments included the St George's Respiratory Questionnaire (SGRQ) and the 6MWT, which were performed yearly. Moreover, clinical complications were recorded to estimate the proportion of the follow-up time lived without clinical intercurrences after transplant. Analyses were performed using adjusted linear regression and repeated-measures analysis of variance. RESULTS: BOS was a significant predictor of lower SGRQ scores (p < 0.01) and reduced time free of clinical complications (p = 0.001), but not of 6MWT distance (p = 0.12). At 7 years post-transplant, results were: 69.0 +/- 21.8% vs 86.9 +/- 5.6%, p < 0.05 (SGRQ); 58.5 +/- 21.6% vs 88.7 +/- 11.4%, p < 0.01 (proportion of time lived without clinical complications); and 82.2 +/- 10.9% vs 91.9 +/- 14.2%, p = 0.27 (percent of predicted 6MWT), respectively, for patients with BOS and without BOS. CONCLUSIONS: Despite significantly less time lived without clinical complications and progressive decline of self-reported health status, the capacity to walk of patients affected by BOS remained relatively stable over time. These findings may indicate that the development of moderate to severe BOS does not prevent lung recipients from walking independently and pursuing an autonomous life.

Adaptive filtering methods for identifying cross-frequency couplings in human EEG.

Oscillations have been increasingly recognized as a core property of neural responses that contribute to spontaneous, induced, and evoked activities within and between individual neurons and neural ensembles. They are considered as a prominent mechanism for information processing within and communication between brain areas. More recently, it has been proposed that interactions between periodic components at different frequencies, known as cross-frequency couplings, may support the integration of neuronal oscillations at different temporal and spatial scales. The present study details methods based on an adaptive frequency tracking approach that improve the quantification and statistical analysis of oscillatory components and cross-frequency couplings. This approach allows for time-varying instantaneous frequency, which is particularly important when measuring phase interactions between components. We compared this adaptive approach to traditional band-pass filters in their measurement of phase-amplitude and phase-phase cross-frequency couplings. Evaluations were performed with synthetic signals and EEG data recorded from healthy humans performing an illusory contour discrimination task. First, the synthetic signals in conjunction with Monte Carlo simulations highlighted two desirable features of the proposed algorithm vs. classical filter-bank approaches: resilience to broad-band noise and oscillatory interference. Second, the analyses with real EEG signals revealed statistically more robust effects (i.e. improved sensitivity) when using an adaptive frequency tracking framework, particularly when identifying phase-amplitude couplings. This was further confirmed after generating surrogate signals from the real EEG data. Adaptive frequency tracking appears to improve the measurements of cross-frequency couplings through precise extraction of neuronal oscillations.

Acute Hospital Bed Capacity - A National Review

The Programme for Prosperity and Fairness outlined the commitment of the Government to a review of hospital bed capacity in both acute and non-acute settings, to be carried out by the Department of Health and Children in conjunction with the Department of Finance and in consultation with the Social Partners. The focus of this report is on bed capacity in publicly-funded acute hospitals in Ireland. The capacity needs of the sub-acute sector have been assessed separately in the context of the Health Strategy, Quality and Fairness: A Health System for You. Download document here

Adaptive Privacy Management System Design For Context-Aware Mobile Devices

While mobile technologies can provide great personalized services for mobile users, they also threaten their privacy. Such personalization-privacy paradox are particularly salient for context aware technology based mobile applications where user's behaviors, movement and habits can be associated with a consumer's personal identity. In this thesis, I studied the privacy issues in the mobile context, particularly focus on an adaptive privacy management system design for context-aware mobile devices, and explore the role of personalization and control over user's personal data. This allowed me to make multiple contributions, both theoretical and practical. In the theoretical world, I propose and prototype an adaptive Single-Sign On solution that use user's context information to protect user's private information for smartphone. To validate this solution, I first proved that user's context is a unique user identifier and context awareness technology can increase user's perceived ease of use of the system and service provider's authentication security. I then followed a design science research paradigm and implemented this solution into a mobile application called "Privacy Manager". I evaluated the utility by several focus group interviews, and overall the proposed solution fulfilled the expected function and users expressed their intentions to use this application. To better understand the personalization-privacy paradox, I built on the theoretical foundations of privacy calculus and technology acceptance model to conceptualize the theory of users' mobile privacy management. I also examined the role of personalization and control ability on my model and how these two elements interact with privacy calculus and mobile technology model. In the practical realm, this thesis contributes to the understanding of the tradeoff between the benefit of personalized services and user's privacy concerns it may cause. By pointing out new opportunities to rethink how user's context information can protect private data, it also suggests new elements for privacy related business models.

Replacement therapy for iron deficiency improves exercise capacity and quality of life in patients with cyanotic congenital heart disease and/or the Eisenmenger syndrome

La teràpia suplementària de ferro millora la capacitat d’exercici i la qualitat de vida en malalts amb una cardiopatia congènita cianòtica i/ o síndrome d’Eisenmenger El dèficit de ferro és una troballa comú en la cardiopatia congènita cianòtica, i pot ser la causa d’una reducció en la capacitat d’exercici. Actualment, està indicada la reposició dels dipòsits de ferro en aquest grup de malalts, éssent les evidències científiques escasses. En el present treball investiguem la seguretat i eficàcia del tractament amb ferro en malalts amb una cardiopatia congènita cianòtica. Per tal motiu, vint-i-cinc malalts amb una cardiopatia congenita cianòtica i dèficit de ferro van ser inclosos de forma prospectiva entre Agost del 2008 i Gener del 2009. El tractament utilitzat fou fumarat ferròs oral, fins a una dosi màxima de 200 mg tres vegades al dia. En l’anàlisi basal i als tres mesos de seguiment es va utilitzar el test de qualitat de vida “CAMPHOR”, el test de la marxa dels 6 minuts i la prova d’esforç amb consum d’oxigen. L’edat mitja fou 39.9+/-10.9 anys, 80% dones. Catorze malalts tenien la síndrome d’Eisenmenger, sis una malaltia cianòtica complexa i cinc circulació de Fontan. Cap d’ells va haver d'interrompre el tractament degut a efectes adversos. Després de tres mesos de tractament, l’hemoglobina (19.0+/-2.9g/dL a 20.4+/-2.7g/dL, p&0.001), ferritina (13.3+/-4.7mug/L a 54.1+/-24.2mug/L, p&0.001) i saturació de transferrina (17.8+/-9.6% a 34.8+/-23.4%, p&0.001) van augmentar significativament. També hi va haver una millora significativa en la puntuació del test de qualitat de vida (20.7+/-10.9 a 16.2+/-10.4, p=0.001) i el test de la marxa (371.7+/-84.7m a 402.8.0+/-74.9m, p=0.001). No es van evidenciar canvis significatius en els valors de consum d’oxigen (40.7+/-9.2% a 43.8+/-12.4%, p=0.15). En definitiva, la teràpia suplementària amb ferro en els malats amb una cardiopatia congènita cianòtica i dèficit de ferro és segura i millora la qualitat de vida i la capacitat funcional. En aquest grup de malalts, per tant, és aconsellable identificar el dèficit de ferro i restaurar-ne els seus dipòsits.