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O objetivo deste trabalho foi avaliar a seletividade dos herbicidas chlorimuron-ethyl, imazethapyr e cloransulam-methyl, aplicados em associação com o herbicida fomesafen, a dez cultivares de feijão. O experimento foi conduzido no município de Rio Verde-GO, no plantio das águas, na safra de 2005/2006. O delineamento experimental utilizado foi de blocos ao acaso, em parcelas subdivididas, com três repetições, sendo o fator da parcela principal os tratamentos com herbicidas [fomesafen (225 g ha-1 ); fomesafen (225 g ha-1 ) + chlorimuron-ethyl (7,5 g ha-1 ); fomesafen (225 g ha-1 ) + imazethapyr (50 g ha-1); fomesafen (225 g ha-1) + cloransulam-methyl (30,24 g ha-1); e testemunha sem herbicida]; e o da subparcela, os cultivares (BRS Grafite, BRS Horizonte, Pérola, BRS Pitanga, BRS Pontal, BRS Requinte, BRS Supremo, BRS Timbó, BRS Valente e BRS Vereda). As parcelas foram mantidas capinadas, para que não houvesse interferência das plantas daninhas. Os tratamentos com herbicidas foram fitotóxicos; todavia, de forma geral, os sintomas mais severos foram verificados no tratamento que continha chlorimuron-ethyl. A associação de fomesafen com chlorimuron-ethyl provocou as maiores reduções na altura das plantas e no acúmulo de massa da parte aérea das plantas secas, além de prolongar o ciclo de maturação de todos os cultivares. A aplicação isolada de fomesafen reduziu a produtividade de grãos dos cultivares BRS Timbó e BRS Vereda. Quando se adicionou o imazethapyr ao fomesafen, observou-se redução na produtividade dos cultivares BRS Supremo, BRS Timbó e BRS Vereda. A adição de cloransulam-methyl, além de reduzir a produtividade desses três cultivares, também diminuiu a produtividade do cultivar BRS Requinte. Os cultivares Pérola, BRS Pitanga, BRS Pontal e BRS Valente não tiveram suas produtividades reduzidas pela mistura chlorimuron-ethyl + fomesafen. O imazethapyr mostrou potencial para ser utilizado na cultura do feijão.This study aimed to evaluate the selectivity of the herbicides chlorimuron-ethyl, imazethapyr and cloransulam-methyl when applied in association with fomesafen on ten common bean cultivars. The experiment was carried out in Rio Verde-Goias during the growing season of 2005/2006, in a completely randomized block design, with three replicates, in split-plots. The herbicide treatments [fomesafen (225 g ha-1 ), fomesafen (225 g ha-1 ) + chlorimuron-ethyl (7.5 g ha-1 ), fomesafen (225 g ha-1 ) + imazethapyr (50 g ha-1 ), fomesafen (225 g ha-1 ) + cloransulam-methyl (30.24 g ha-1 ), and control without herbicide] were tested in the plots and the cultivars (BRS Grafite, BRS Horizonte, Pérola, BRS Pitanga, BRS Pontal, BRS Requinte, BRS Supremo, BRS Timbó, BRS Valente and BRS Vereda), in the split-plots. The plots were kept hoed to avoid weed interference. All treatments caused phytotoxicity to the cultivars, but the treatment with chlorimuron-ethyl showed more severe symptoms. This same treatment also resulted in greater reduction of plant height, shoot dry matter and an extended maturation cycle. The sole application of fomesafen caused a decrease in grain productivity of BRS Timbó, and BRS Vereda. When fomesafen was applied in a mixture with imazethapyr, a decrease in grain productivity was observed for the cultivars BRS Timbó, BRS Vereda, and BRS Supremo. Cloransulam-methyl addition led to a productivity reduction of these three cultivars and BRS Requinte, as well. The productivity of Pérola, BRS Pitanga, BRS Pontal, and BRS Valente cultivars was not affected by the application of chlorimuron-ethyl + fomesafen. Imazethapyr presented potential to be used in common bean crop.

Objetivou-se com este trabalho avaliar a eficácia e a seletividade da associação dos herbicidas chlorimuron-ethyl e imazethapyr ao glyphosate no controle de plantas daninhas na cultura da soja Roundup Ready® (RR®). O experimento foi realizado no Centro Tecnológico da COMIGO, localizado no município de Rio Verde-GO, na safra 2005/2006. A semeadura do cultivar Monsoy 7878 foi realizada mecanicamente, sendo a semeadora regulada para liberar 18 sementes por metro. O espaçamento utilizado entre linhas foi de 0,50 m. O delineamento experimental foi o de blocos ao acaso, com quatro repetições. A aplicação isolada de glyphosate nas doses de 480, 960 e 1.440 g ha-1 não causou intoxicação e não reduziu a altura e o acúmulo de massa seca das plantas de soja RR®. A adição dos herbicidas imazethapyr e chlorimuron-ethyl ao glyphosate ocasionou intoxicação às plantas de soja RR®, todavia em níveis aceitáveis, sendo os sintomas provocados pela ação do imazethapyr mais intensos em comparação aos do chlorimuron-ethyl. A associação do herbicida imazethapyr ao glyphosate reduziu a altura e o acúmulo de fitomassa das plantas de soja RR®. A aplicação isolada de glyphosate nas doses de 480, 960 e 1.440 g ha-1 não apresentou controle satisfatório das plantas daninhas Euphorbia heterophylla, Commelina benghalensis, Chamaesyce hirta, Leucas martinicensis e Ipomoea grandifolia. Apesar de incrementar o controle da maioria das plantas daninhas, a adição dos herbicidas chlorimuron-ethyl e imazethapyr ao glyphosate não promoveu aumento de produtividade de grãos na cultura da soja RR®.The objective of this work was to evaluate the efficacy and selectivity of the herbicides chlorimuron-ethyl and imazethapyr associated to glyphosate in controlling weeds on Roundup Ready (RR®) soybean crop. The experiment was carried out at the COMIGO Technological Center in Rio Verde-GO, during the 2005/2006-crop season. The variety used was Monsoy 7878 which had 18 seeds mechanically distributed per meter. The rows were spaced by 0.50 m. The experiment was arranged in a completely randomized block design with four replications for each treatment. Glyphosate doses (480, 960 and 1.440 g ha-1), applied alone, did not cause plant toxicity nor reduced height and biomass accumulation of RR® soybean plants. However, the addition of the herbicides imazethapyr and chlorimuron-ethyl to glyphosate caused plant toxicity in the soybean RR® plants, though at an acceptable degree. The symptoms caused by imazethapyr were more severe than those caused by chlorimuron-ethyl. The association of imazethapyr and glyphosate led to reduced height and biomass. The application of glyphosate alone at doses 480, 960 and 1.440 g ha-1, did not exert sufficient control over Euphorbia heterophylla, Commelina benghalensis, Chamaesyce hirta, Leucas martinicensis and Ipomoea grandifolia. Despite increasing control of most of the weeds, chlorimuron-ethyl and imazethapyr addition did not promote increased yield when applied on the RR® soybean crop.

Active Disturbance Rejection Control (ADRC) is a very promising recent concept for the design of controllers to control systems with uncertainties. Based on an extended state observer, this control structure allows both external disturbances and modeling uncertainties to be actively rejected. The use of the active rejection control of disturbances is gaining more and more interest among the system control community. This is mainly due to its easy design, undemanding implementation and robustness. In this paper, three solutions using the ARDC structure to control fractional-order system are discussed. Two methods taken from the literature are briefly introduced, namely, the fractional-order dynamics rejection scheme (FODRS) and the fractional linear active disturbance rejection control (FLADRC). The basic ideas and technical formulations of these two are presented. A third method, based on the robustness performance introduced by fractional-order controllers, is also proposed in this paper. The proposed design method of the set-point tracking controller is based on the Bode’s ideal transfer function (Bode’s ITF). This will improve the robustness of the control scheme.

Failure due to fatigue and lock up risks for drilling pipes in tortuous trajectory is a very costly problem in oil and gas industry, since the cyclic loading which occurs while rotating bent drill pipes in a dog leg are more dangerous than rotating buckled drill pipes. This study is aimed to assess these risks and determine whether by integrating 2024 aluminium alloy drill pipes in drilling string, it is possible to extend the drilling operation without having detrimental impact on the drilling string integrity. Accordingly, the obtained results showed that, even though steel drill pipes have better mechanical properties, compared to 2024 aluminium alloy drill pipes, the latter have a better fatigue resistance even in the simultaneous presence of high applied torque and axial load, and severe dog-legs, beside good resistance to wear and corrosion even at high temperature, thereby reducing environmental trash and full consumption in order to minimise pollution.

Bearing in mind the considerable distances between natural gas fields and consumers’ appliances, transport by gas pipelines remains the most competitive means. These gas pipelines which are generally made of steel pipes may contain however several types of defects of various origins and which are susceptible to initiate cracks which may grow under some circumstances to such extent as to lead to fracture. Failures of gas pipelines may have serious consequences and may lead to catastrophes from ecological and financial viewpoints. It is therefore interesting to study the defect admissibility so as to maximize safety and minimize exploitation costs through a simplified method based on the Failure Assessment Diagram (FAD). The latter is used in conjunction with Finite Element Analysis (FEM) applied to fracture mechanics to help decision making as to whether a given defect present in a pipe is acceptable or not.

The economic performance of petroleum products transport companies is dependent on the reliability of their equipment. Ruptures of the weld joints of petroleum products carriage pipelines have major consequences at the human, environmental and economic levels. Weld joints are potential sites of dangerous cracks. The management of reliability of weld joints in pipelines is useful to integrate the quality planning and risks throughout their life cycle and to systematically track their characteristics all along their life cycles. The use in situ of inspection results from non-destructive control techniques is an essential component of evaluation and control of reliability of pipes in their function. It requires calculation methods and tools to assist in the decision-making in support of inspection and repair campaigns. It is in this context that the present study was conducted, which is a contribution to the efforts of methodological assessment of the reliability of petroleum products transport pipelines.

The growing oil demand requires the construction of new pipes of large diameters, to carry large quantities of oil and natural gas to consumers. This has led industrialists to manufacture high resistance steel tubes. On the other hand to increase the capacity of pipelines, it is necessary to increase the operating pressure. Ensuring high reliability of pressure pipes requires a significant increase in pipe wall thickness, and the development of high-quality rolled steels. In this context the choice of pipes for the construction of the oil transporting pipelines require a reliability approach, showing explicitly the dependency between increase in the pipe wall thickness and the pipelines reliability improvement. This issue is the subject of the current study, which is dedicated to the formulation and analysis of the problem, where by the methods of structures reliability and mathematical statistics, one determines quantitative indices of reliability of pipes which are used in comparing different variants in order to select the best solution. Such an approach allows specifying, at the projection and construction stages, the requirements of proper working of hydrocarbons transport pipelines.

Problems of hydrocarbons transporting pipelines aging and rehabilitation are currently a major concern for operators of such installations. Rehabilitating and insuring hydrocarbons transporting pipelines, require interventions, such as the renovation of existing lines, the replacement of some pipelines with new ones, in order to meet the growing demand of consumers and improve the supply reliability. In this context, a decision to repair or replace a section of pipe must combine both a technical analysis of failures and sound economic analysis of the choice of possible interventions, which is the purpose of this study, dedicated to research and policy determination of repair and replacement of aged pipe sections, taking into account the factors mentioned above, and based on significant feedback.

The actions of the various phenomena of corrosion, mechanical constraints and others, contribute to the degradation of hydrocarbons transportation ducts. The combinations of these phenomena accelerate pipe ageing, and this results in the increase of the frequency of leaks interventions and pipe ruptures. The only way to struggle against the ageing of oil transportation pipelines is the rehabilitation. This will allow the re-servicing of pipes whose resistance characteristics are degraded. One of the major difficulties, during the conception of a pipeline rehabilitation program, is the determination of the specific sections to rehabilitate. Indeed if there is any real risk not to do enough rehabilitation in the one hand, there is a risk to bad rehabilitation on the other. The decision to continue to maintain, renovate or replace some degraded sections of a pipeline is not an easy task, and requires development of forecasting models that will enable decision-makers to take the right decisions on the middle and long term. In this context, this study is devoted to analysis of problems associated with statistical exploitation of controls and repair files of aged pipes, establishing action plans and controlling the ageing of hydrocarbons transportation pipelines.

Il s’agit dans ce travail, de la mise en place d’un banc d’essai expérimental d’un modèle de distillateur plan à effet de serre. Le problème à traiter consiste à améliorer la production d’eau distillée en apportant des modifications sur ce nouveau modèle de distillateur avec l’utilisation d’un réflecteur plan pour augmenter le flux solaire global reçu, l’utilisation d’un système de préchauffage d’eau d’appoint du distillateur et enfin l’utilisation d’un absorbeur ondulé pour augmenter la surface d’absorption du flux solaire. Une série de tests a été effectuée pour connaître l’efficacité apportée par chacun de ces éléments.

The environmental impact of livestock is often evaluated separately from the other agricultural activities involved in an integrated system, such as that of the rearing of Piemontese cattle in the area of origin of the breed. The most frequently used assessment methods (e.g. Footprint approaches or a Life Cycle Assessment) are in fact often used, through a product-based approach, to analyse a single productive process, but such methods do not consider the production of agro-ecological services, and they neglect the interactions that characterise complex systems. Moreover, such methods often only consider the negative aspects of the environmental impact and misrepresent less intensive agriculture practices. However the current gaps in knowledge about the carbon sequestration of agricultural ecosystems, which are complex and integrated systems, require further investigation and other types of analysis tools. A carbon (C) balance of 1223 Piemontese breed beef farms, located in North-West Italy, has been calculated to evaluate whether such a method could be applied to overcome the aforementioned limitations, to evaluate whether it could be used to describe a complex and integrated system, to highlight the relationships that exist between rearing and agricultural activities and to characterise their environmental roles. Conducting a mass balance involves considering the input and output material flows and their accumulation within a system. Thus, the data necessary to quantify the C input, output and internal fluxes of a system at the farm gate, pertaining to the vegetable and animal production processes (productive factors, crop yields, animal performances, productions and sales, reuses), were collected from official documentation, and were then completed and verified through site visits. The mass balance of the system was transformed into C fluxes using stoichiometric coefficients. The fluxes evaluated for the balance were then used to estimate the changes in the C stocks to highlight not only the C emissions or losses from the system, but also their contributions towards reducing environmental hazards. A sensitivity analysis was carried out to evaluate the uncertainty and the robustness of the obtained results. The net C exchange from plants was the flux that contributed the most, amounting to 94.3 % of the inputs, and this was followed by soil losses and animal gases released through respiration and enteric fermentation, which amounted to 42.8 and 36.2 % of the outputs, respectively. The C stored and released by the considered system was calculated considering the C fluxes. Plant, animal and soil storage sites were included in the system, whereas the air site was left out. A constant C content was assumed for the soil. The productive activities of the selected group of beef farms in the Consortium were calculated to remove 96.1 10 3  t of C from the atmosphere (air site) over a period of one year, and that this amount of C was transferred to plant growth and agricultural products (plant site) and to an increase in live weight (LW) of the animals (animal site). The rates of the stored C to agricultural and wooded areas and to the LW of the animals slaughtered in one year were 1.18 t ha -1 and 2.24 t C t -1 LW, respectively. The sensitivity analysis demonstrated that the C balance was always positive, even for the worst scenario. This study has shown that the examined beef production system, when analysed as an integrated and complex system, can be considered an important C sink and that it is necessary to reconsider the role that livestock, and ruminants in particular, play in the global greenhouse effect., Competing Interests: Declaration of competing interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Studies using scalp EEG have shown that slow waves (0.5-4 Hz), the most prominent hallmark of NREM sleep, undergo relevant changes from childhood to adulthood, mirroring brain structural modifications and the acquisition of cognitive skills. Here we used simultaneous EEG-fMRI to investigate the cortical and subcortical correlates of slow waves in school-age children and determine their relative developmental changes., Methods: We analyzed data from 14 school-age children with self-limited focal epilepsy of childhood who fell asleep during EEG-fMRI recordings. Brain regions associated with slow-wave occurrence were identified using a voxel-wise regression that also modelled interictal epileptic discharges and sleep spindles. At the group level, a mixed-effects linear model was used. The results were qualitatively compared with those obtained from 2 adolescents with epilepsy and 17 healthy adults., Results: Slow waves were associated with hemodynamic-signal decreases in bilateral somatomotor areas. Such changes extended more posteriorly relative to those in adults. Moreover, the involvement of areas belonging to the default mode network changes as a function of age. No significant hemodynamic responses were observed in subcortical structures. However, we identified a significant correlation between age and thalamic hemodynamic changes., Conclusions: Present findings indicate that the somatomotor cortex may have a key role in slow-wave expression throughout the lifespan. At the same time, they are consistent with a posterior-to-anterior shift in slow-wave distribution mirroring brain maturational changes. Finally, our results suggest that slow-wave changes may not reflect only neocortical modifications but also the maturation of subcortical structures, including the thalamus., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the regulations of our institutions concerning intellectual property., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Rationale: It is currently unclear which patients with obstructive sleep apnea (OSA) are at increased cardiovascular risk. Objective: To investigate the value of pulse wave amplitude drops (PWADs), reflecting sympathetic activations and vasoreactivity, as a biomarker of cardiovascular risk in OSA. Methods: PWADs were derived from pulse oximetry-based photoplethysmography signals in three prospective cohorts: HypnoLaus ( N  = 1,941), the Pays-de-la-Loire Sleep Cohort (PLSC; N  = 6,367), and "Impact of Sleep Apnea syndrome in the evolution of Acute Coronary syndrome. Effect of intervention with CPAP" (ISAACC) ( N  = 692). The PWAD index was the number of PWADs (>30%) per hour during sleep. All participants were divided into subgroups according to the presence or absence of OSA (defined as ⩾15 or more events per hour or <15/h, respectively, on the apnea-hypopnea index) and the median PWAD index. Primary outcome was the incidence of composite cardiovascular events. Measurements and Main Results: Using Cox models adjusted for cardiovascular risk factors (hazard ratio; HR [95% confidence interval]), patients with a low PWAD index and OSA had a higher incidence of cardiovascular events compared with the high-PWAD and OSA group and those without OSA in the HypnoLaus cohort (HR, 2.16 [1.07-4.34], P  = 0.031; and 2.35 [1.12-4.93], P  = 0.024) and in the PLSC (1.36 [1.13-1.63], P  = 0.001; and 1.44 [1.06-1.94], P  = 0.019), respectively. In the ISAACC cohort, the low-PWAD and OSA untreated group had a higher cardiovascular event recurrence rate than that of the no-OSA group (2.03 [1.08-3.81], P  = 0.028). In the PLSC and HypnoLaus cohorts, every increase of 10 events per hour in the continuous PWAD index was negatively associated with incident cardiovascular events exclusively in patients with OSA (HR, 0.85 [0.73-0.99], P  = 0.031; and HR, 0.91 [0.86-0.96], P  < 0.001, respectively). This association was not significant in the no-OSA group and the ISAACC cohort. Conclusions: In patients with OSA, a low PWAD index reflecting poor autonomic and vascular reactivity was independently associated with a higher cardiovascular risk.

Aim: In response to the SARS-CoV-2 emergency, the Competence Centre on digital health 'TrentinoSalute4.0' has developed TreC&#95;Televisita, a tele visit solution that meets the needs of the Trentino healthcare system and maintains high-quality patient-doctor interactions while respecting social distancing. This paper highlights how 'TreC&#95;Televisita' was integrated into the Trentino healthcare system and its potential to become a structural and durable solution for the future local healthcare service provisioning., Subject and Methods: This paper presents the multifactorial context that TreC&#95;Televisita has faced for its implementation and the strategies adopted for its structural integration into the healthcare system. The analysis focuses on the main issues faced for the integration of the tele visits (e.g. privacy, payments) and how the context of TrentinoSalute4.0 permitted responding quickly to its implementation during the pandemic. It also describes how TreC&#95;Televisita fits into the healthcare continuum from the organisational and technological standpoint, the end-user perspective and the barriers that could hamper the solution scalability., Results: TreC&#95;Televisita has demonstrated to be a technological solution that can be contextualised for different clinical domains beyond SARS-CoV-2. Moreover, it has shown its potential to scale up the solution beyond the COVID-19 emergency to the whole healthcare provisioning system in the long term., Conclusion: Being a positive experience in the first months of its implementation, the long-term goal is to transform TreC&#95;Televisita into a structural pillar of the Trentino healthcare system, setting the bases for a sustainable, win-win situation for all the stakeholders involved in healthcare service provisioning., Competing Interests: Conflicts of interest/competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2021.)

EEG slow waves, the hallmarks of NREM sleep are thought to be crucial for the regulation of several important processes, including learning, sensory disconnection and the removal of brain metabolic wastes. Animal research indicates that slow waves may involve complex interactions within and between cortical and subcortical structures. Conventional EEG in humans, however, has a low spatial resolution and is unable to accurately describe changes in the activity of subcortical and deep cortical structures. To overcome these limitations, here we took advantage of simultaneous EEG-fMRI recordings to map cortical and subcortical hemodynamic (BOLD) fluctuations time-locked to slow waves of light sleep. Recordings were performed in twenty healthy adults during an afternoon nap. Slow waves were associated with BOLD-signal increases in the posterior brainstem and in portions of thalamus and cerebellum characterized by preferential functional connectivity with limbic and somatomotor areas, respectively. At the cortical level, significant BOLD-signal decreases were instead found in several areas, including insula and somatomotor cortex. Specifically, a slow signal increase preceded slow-wave onset and was followed by a delayed, stronger signal decrease. Similar hemodynamic changes were found to occur at different delays across most cortical brain areas, mirroring the propagation of electrophysiological slow waves, from centro-frontal to inferior temporo-occipital cortices. Finally, we found that the amplitude of electrophysiological slow waves was positively related to the magnitude and inversely related to the delay of cortical and subcortical BOLD-signal changes. These regional patterns of brain activity are consistent with theoretical accounts of the functions of sleep slow waves., Competing Interests: Declaration of Competing Interests The authors report no competing interests., (Copyright © 2021. Published by Elsevier Inc.)

Functional connectivity (FC) metrics describe brain inter-regional interactions and may complement information provided by common power-based analyses. Here, we investigated whether the FC-metrics weighted Phase Lag Index (wPLI) and weighted Symbolic Mutual Information (wSMI) may unveil functional differences across four stages of vigilance-wakefulness (W), NREM-N2, NREM-N3, and REM sleep-with respect to each other and to power-based features. Moreover, we explored their possible contribution in identifying differences between stages characterized by distinct levels of consciousness (REM+W vs. N2+N3) or sensory disconnection (REM vs. W). Overnight sleep and resting-state wakefulness recordings from 24 healthy participants (27 ± 6 years, 13F) were analyzed to extract power and FC-based features in six classical frequency bands. Cross-validated linear discriminant analyses (LDA) were applied to investigate the ability of extracted features to discriminate (1) the four vigilance stages, (2) W+REM vs. N2+N3, and (3) W vs. REM. For the four-way vigilance stages classification, combining features based on power and both connectivity metrics significantly increased accuracy relative to considering only power, wPLI, or wSMI features. Delta-power and connectivity (0.5-4 Hz) represented the most relevant features for all the tested classifications, in line with a possible involvement of slow waves in consciousness and sensory disconnection. Sigma-FC, but not sigma-power (12-16 Hz), was found to strongly contribute to the differentiation between states characterized by higher (W+REM) and lower (N2+N3) probabilities of conscious experiences. Finally, alpha-FC resulted as the most relevant FC-feature for distinguishing among wakefulness and REM sleep and may thus reflect the level of disconnection from the external environment., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Although excessive daytime sleepiness is commonly evaluated in clinical and research settings using the Epworth Sleepiness Scale, few studies have assessed the factors associated with its incidence in the general population. We prospectively investigated the predictors of incident and persistent excessive daytime sleepiness in 2,751 subjects (46.1% men, mean age 56.0 ± 9.8 years) from the CoLaus-PsyCoLaus population-based cohort (Lausanne, Switzerland) over 5 years. Participants completed the Epworth Sleepiness Scale and the Pittsburgh Sleep Quality Index, and underwent a full clinical evaluation at baseline and 5 years afterwards. Ambulatory polysomnography was performed at baseline in a sub-sample of 1,404 subjects. Among the 2,438 subjects without excessive daytime sleepiness (Epworth Sleepiness Scale ≤ 10) at baseline, the 5-year incidence of excessive daytime sleepiness was 5.1% (n = 124). Multivariate logistic regression revealed that male sex, depressive symptoms, reported poor sleep quality and moderate to severe obstructive sleep apnea were independent predictors of incident excessive daytime sleepiness, while older age, moderate coffee consumption, periodic leg movement during sleep and hypertension were independent protective factors. Stratified analysis according to sex and age showed some distinctive associations. Among the 313 patients with excessive daytime sleepiness at baseline, 137 (43.8%) had persistent excessive daytime sleepiness 5 years later. Our findings provide new insights into the predictors of incident excessive daytime sleepiness, but interventional studies are needed to understand the impact of treating these risk factors on the incidence of excessive daytime sleepiness., (© 2020 European Sleep Research Society.)

Feeling awake although sleep recordings indicate clear-cut sleep sometimes occurs in good sleepers and to an extreme degree in patients with so-called paradoxical insomnia. It is unknown what underlies sleep misperception, as standard polysomnographic (PSG) parameters are often normal in these cases. Here we asked whether regional changes in brain activity could account for the mismatch between objective and subjective total sleep times (TST). To set cutoffs and define the norm, we first evaluated sleep perception in a population-based sample, consisting of 2,092 individuals who underwent a full PSG at home and estimated TST the next day. We then compared participants with a low mismatch (normoestimators, n = 1,147, ±0.5 SD of mean) with those who severely underestimated (n = 52, <2.5th percentile) or overestimated TST (n = 53, >97.5th percentile). Compared with normoestimators, underestimators displayed higher electroencephalographic (EEG) activation (beta/delta power ratio) in both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep, while overestimators showed lower EEG activation (significant in REM sleep). To spatially map these changes, we performed a second experiment, in which 24 healthy subjects and 10 insomnia patients underwent high-density sleep EEG recordings. Similarly to underestimators, patients displayed increased EEG activation during NREM sleep, which we localized to central-posterior brain areas. Our results indicate that a relative shift from low- to high-frequency spectral power in central-posterior brain regions, not readily apparent in conventional PSG parameters, is associated with underestimation of sleep duration. This challenges the concept of sleep misperception, and suggests that instead of misperceiving sleep, insomnia patients may correctly perceive subtle shifts toward wake-like brain activity., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

The slow waves of non-rapid eye movement (NREM) sleep reflect experience-dependent plasticity and play a direct role in the restorative functions of sleep. Importantly, slow waves behave as traveling waves, and their propagation is assumed to occur through cortico-cortical white matter connections. In this light, the corpus callosum (CC) may represent the main responsible for cross-hemispheric slow-wave propagation. To verify this hypothesis, we performed overnight high-density (hd)-EEG recordings in five patients who underwent total callosotomy due to drug-resistant epilepsy (CPs; two females), in three noncallosotomized neurologic patients (NPs; two females), and in a sample of 24 healthy adult subjects (HSs; 13 females). In all CPs slow waves displayed a significantly reduced probability of cross-hemispheric propagation and a stronger inter-hemispheric asymmetry. In both CPs and HSs, the incidence of large slow waves within individual NREM epochs tended to differ across hemispheres, with a relative overall predominance of the right over the left hemisphere. The absolute magnitude of this asymmetry was greater in CPs relative to HSs. However, the CC resection had no significant effects on the distribution of slow-wave origin probability across hemispheres. The present results indicate that CC integrity is essential for the cross-hemispheric traveling of slow waves in human sleep, which is in line with the assumption of a direct relationship between white matter integrity and slow-wave propagation. Our findings also revealed a residual cross-hemispheric slow-wave propagation that may rely on alternative pathways, including cortico-subcortico-cortical loops. Finally, these data indicate that the lack of the CC does not lead to differences in slow-wave generation across brain hemispheres. SIGNIFICANCE STATEMENT The slow waves of NREM sleep behave as traveling waves, and their propagation has been suggested to reflect the integrity of white matter cortico-cortical connections. To directly assess this hypothesis, here we investigated the role of the corpus callosum in the cortical spreading of NREM slow waves through the study of a rare population of totally callosotomized patients. Our results demonstrate a causal role of the corpus callosum in the cross-hemispheric traveling of sleep slow waves. Additionally, we found that callosotomy does not affect the relative tendency of each hemisphere at generating slow waves. Incidentally, we also found that slow waves tend to originate more often in the right than in the left hemisphere in both callosotomized and healthy adult individuals., (Copyright © 2020 Avvenuti et al.)

Study Objectives: To explore the clinical significance of pulse wave amplitude (PWA)-drops during sleep as a biomarker for cardiometabolic disorders and describe their main characteristics in a general population sample., Methods: Cross-sectional study of HypnoLaus cohort, in which 2162 individuals underwent clinical assessment and in-home full polysomnography. PWA-drops were derived from photoplethysmography and processed using a validated automated algorithm. Associations between PWA-drop features (index, mean duration, and mean area under the curve [AUC]) with hypertension, diabetes, and previous cardiovascular (CV) event were analyzed using multivariable-adjusted logistic regression., Results: Two thousand one hundred forty-nine participants (59 ± 11 years, 51% women, 9.9% diabetes, 41.3% hypertension, 4.4% CV event) were included. Mean ± standard deviation (SD) of PWA-drop index, duration, and AUC during sleep were 51.0 ± 20.3 events/hour, 14.0 ± 2.7 seconds, and 527±115 %seconds, respectively. PWA-drop index was lower in women and decreased with age, while its mean duration and AUC increased in men and elderly. Overall, lower PWA-drop index, longer duration and greater AUC were associated with increased odds of hypertension, diabetes, or CV event after adjustment for confounders. Participants in the lowest quartile of mean duration-normalized PWA-drop index had a significantly higher odds ratio (OR) of hypertension (OR = 1.60 [1.19-2.16]), CV event (OR = 3.26 [1.33-8.03]), and diabetes (OR = 1.71 [1.06-2.76]) compared to those in the highest quartile. Similar results were observed for mean AUC-normalized PWA-drop index regarding hypertension (OR = 1.59 [1.19-2.13]), CV event (OR = 2.45 [1.14-5.26]) and diabetes (OR = 1.76 [1.10-2.83])., Conclusions: PWA-drop features during sleep seem to be an interesting biomarker independently associated with cardiometabolic outcomes in the general population., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society.)

Sudden drops in pulse wave amplitude (PWA) measured by finger photoplethysmography (PPG) are known to reflect peripheral vasoconstriction resulting from sympathetic activation. Previous work demonstrated that sympathetic activations during sleep typically accompany the occurrence of pathological respiratory and motor events, and their alteration may be associated with the arising of metabolic and cardiovascular diseases. Importantly, PWA-drops often occur in the absence of visually identifiable cortical micro-arousals and may thus represent a more accurate marker of sleep disruption/fragmentation. In this light, an objective and reproducible quantification and characterization of sleep-related PWA-drops may offer a valuable, non-invasive approach for the diagnostic and prognostic evaluation of patients with sleep disorders. However, the manual identification of PWA-drops represents a time-consuming practice potentially associated with high intra/inter-scorer variability. Since validated algorithms are not readily available for research and clinical purposes, here we present a novel automated approach to detect and characterize significant drops in the PWA-signal. The algorithm was tested against expert human scorers who visually inspected corresponding PPG-recordings. Results demonstrated that the algorithm reliably detects PWA-drops and is able to characterize them in terms of parameters with a potential physiological and clinical relevance, including timing, amplitude, duration and slopes. The method is completely user-independent, processes all-night PSG-data, automatically dealing with potential artefacts, sensor loss/displacements, and stage-dependent variability in PWA-time-series. Such characteristics make this method a valuable candidate for the comparative investigation of large clinical datasets, to gain a better insight into the reciprocal links between sympathetic activity, sleep-related alterations, and metabolic and cardiovascular diseases., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Humans use emotions to decipher complex cascades of internal events. However, which mechanisms link descriptions of affective states to brain activity is unclear, with evidence supporting either local or distributed processing. A biologically favorable alternative is provided by the notion of gradient, which postulates the isomorphism between functional representations of stimulus features and cortical distance. Here, we use fMRI activity evoked by an emotionally charged movie and continuous ratings of the perceived emotion intensity to reveal the topographic organization of affective states. Results show that three orthogonal and spatially overlapping gradients encode the polarity, complexity and intensity of emotional experiences in right temporo-parietal territories. The spatial arrangement of these gradients allows the brain to map a variety of affective states within a single patch of cortex. As this organization resembles how sensory regions represent psychophysical properties (e.g., retinotopy), we propose emotionotopy as a principle of emotion coding.

Background The contribution of the lung or the plant gain ( PG ; ie, change in blood gases per unit change in ventilation) to Cheyne-Stokes respiration ( CSR ) in heart failure has only been hypothesized by mathematical models, but never been directly evaluated. Methods and Results Twenty patients with systolic heart failure (age, 72.4±6.4 years; left ventricular ejection fraction, 31.5±5.8%), 10 with relevant CSR (24-hour apnea-hypopnea index [ AHI ] ≥10 events/h) and 10 without ( AHI <10 events/h) at 24-hour cardiorespiratory monitoring underwent evaluation of chemoreflex gain (CG) to hypoxia ([Formula: see text]) and hypercapnia ([Formula: see text]) by rebreathing technique, lung-to-finger circulation time, and PG assessment through a visual system. PG test was feasible and reproducible (intraclass correlation coefficient, 0.98; 95% CI , 0.91-0.99); the best-fitting curve to express the PG was a hyperbola ( R 2 ≥0.98). Patients with CSR showed increased PG , [Formula: see text] (but not [Formula: see text]), and lung-to-finger circulation time, compared with patients without CSR (all P<0.05). PG was the only predictor of the daytime AHI ( R=0.56, P=0.01) and together with the [Formula: see text] also predicted the nighttime AHI ( R=0.81, P=0.0003) and the 24-hour AHI ( R=0.71, P=0.001). Lung-to-finger circulation time was the only predictor of CSR cycle length ( R=0.82, P=0.00006). Conclusions PG is a powerful contributor of CSR and should be evaluated together with the CG and circulation time to individualize treatments aimed at stabilizing breathing in heart failure.

The weighted Phase Lag Index (wPLI) and the weighted Symbolic Mutual Information (wSMI) represent two robust and widely used methods for MEG/EEG functional connectivity estimation. Interestingly, both methods have been shown to detect relative alterations of brain functional connectivity in conditions associated with changes in the level of consciousness, such as following severe brain injury or under anaesthesia. Despite these promising findings, it was unclear whether wPLI and wSMI may account for distinct or similar types of functional interactions. Using simulated high-density (hd-)EEG data, we demonstrate that, while wPLI has high sensitivity for couplings presenting a mixture of linear and nonlinear interdependencies, only wSMI can detect purely nonlinear interaction dynamics. Moreover, we evaluated the potential impact of these differences on real experimental data by computing wPLI and wSMI connectivity in hd-EEG recordings of 12 healthy adults during wakefulness and deep (N3-)sleep, characterised by different levels of consciousness. In line with the simulation-based findings, this analysis revealed that both methods have different sensitivity for changes in brain connectivity across the two vigilance states. Our results indicate that the conjoint use of wPLI and wSMI may represent a powerful tool to study the functional bases of consciousness in physiological and pathological conditions.

Previous studies have shown that regional slow-wave activity (SWA) during non-rapid eye movement (NREM) sleep is modulated by prior experience and learning. Although this effect has been convincingly demonstrated for the sensorimotor domain, attempts to extend these findings to the visual system have provided mixed results. In this study we asked whether depriving subjects of external visual stimuli during daytime would lead to regional changes in slow waves during sleep and whether the degree of "internal visual stimulation" (spontaneous imagery) would influence such changes. In two 8-h sessions spaced 1 wk apart, 12 healthy volunteers either were blindfolded while listening to audiobooks or watched movies (control condition), after which their sleep was recorded with high-density EEG. We found that during NREM sleep, the number of small, local slow waves in the occipital cortex decreased after listening with blindfolding relative to movie watching in a way that depended on the degree of visual imagery subjects reported during blindfolding: subjects with low visual imagery showed a significant reduction of occipital sleep slow waves, whereas those who reported a high degree of visual imagery did not. We also found a positive relationship between the reliance on visual imagery during blindfolding and audiobook listening and the degree of correlation in sleep SWA between visual areas and language-related areas. These preliminary results demonstrate that short-term alterations in visual experience may trigger slow-wave changes in cortical visual areas. Furthermore, they suggest that plasticity-related EEG changes during sleep may reflect externally induced ("bottom up") visual experiences, as well as internally generated ("top down") processes. NEW & NOTEWORTHY Previous work has shown that slow-wave activity, a marker of sleep depth, is linked to neural plasticity in the sensorimotor cortex. We show that after short-term visual deprivation, subjects who reported little visual imagery had a reduced incidence of occipital slow waves. This effect was absent in subjects who reported strong spontaneous visual imagery. These findings suggest that visual imagery may "substitute" for visual perception and induce similar changes in non-rapid eye movement slow waves.

Biological vision relies on representations of the physical world at different levels of complexity. Relevant features span from simple low-level properties, as contrast and spatial frequencies, to object-based attributes, as shape and category. However, how these features are integrated into coherent percepts is still debated. Moreover, these dimensions often share common biases: for instance, stimuli from the same category (e.g., tools) may have similar shapes. Here, using magnetoencephalography, we revealed the temporal dynamics of feature processing in human subjects attending to objects from six semantic categories. By employing Relative Weights Analysis, we mitigated collinearity between model-based descriptions of stimuli and showed that low-level properties (contrast and spatial frequencies), shape (medial-axis) and category are represented within the same spatial locations early in time: 100-150 ms after stimulus onset. This fast and overlapping processing may result from independent parallel computations, with categorical representation emerging later than the onset of low-level feature processing, yet before shape coding. Categorical information is represented both before and after shape, suggesting a role for this feature in the refinement of categorical matching.

The introduction of mass vaccination against Varicella-Zoster-Virus (VZV) is being delayed in many European countries mainly because of the "fear" of a subsequent boom in natural herpes zoster (HZ) incidence in the first decades after the initiation of vaccination, caused by the expected decline in the protective effect of natural immunity boosting due to reduced virus circulation. Optimal control theory has proven to be a successful tool in understanding ways to curtail the spread of infectious diseases by devising the optimal disease intervention strategies. In this paper, we describe how a reduced 'toy' model can extract the essentials of the dynamics of the VZV transmission and reactivation in case of the study of optimal paths of varicella immunization programs. Results obtained using different optimization approaches are compared with the ones of a more realistic age-structured model. The reduced model shows some unreliable predictions in regards of model time scales about herpes zoster dynamic; nevertheless, it is able to reproduce the main qualitative dynamic of the more realistic model to the different optimization problems, while requiring a minimal number of parameters to be identified. Graphical abstract ᅟ.

Although the EEG slow wave of sleep is typically considered to be a hallmark of nonrapid eye movement (NREM) sleep, recent work in mice has shown that slow waves can also occur in REM sleep. Here, we investigated the presence and cortical distribution of negative delta (1-4 Hz) waves in human REM sleep by analyzing high-density EEG sleep recordings obtained in 28 healthy subjects. We identified two clusters of delta waves with distinctive properties: (1) a frontal-central cluster characterized by ∼2.5-3.0 Hz, relatively large, notched delta waves (so-called "sawtooth waves") that tended to occur in bursts, were associated with increased gamma activity and rapid eye movements (EMs), and upon source modeling displayed an occipital-temporal and a frontal-central component and (2) a medial-occipital cluster characterized by more isolated, slower (<2 Hz), and smaller waves that were not associated with rapid EMs, displayed a negative correlation with gamma activity, and were also found in NREM sleep. Therefore, delta waves are an integral part of REM sleep in humans and the two identified subtypes (sawtooth and medial-occipital slow waves) may reflect distinct generation mechanisms and functional roles. Sawtooth waves, which are exclusive to REM sleep, share many characteristics with ponto-geniculo-occipital waves described in animals and may represent the human equivalent or a closely related event, whereas medial-occipital slow waves appear similar to NREM sleep slow waves. SIGNIFICANCE STATEMENT The EEG slow wave is typically considered a hallmark of nonrapid eye movement (NREM) sleep, but recent work in mice has shown that it can also occur in REM sleep. By analyzing high-density EEG recordings collected in healthy adult individuals, we show that REM sleep is characterized by prominent delta waves also in humans. In particular, we identified two distinctive clusters of delta waves with different properties: a frontal-central cluster characterized by faster, activating "sawtooth waves" that share many characteristics with ponto-geniculo-occipital waves described in animals and a medial-occipital cluster containing slow waves that are more similar to NREM sleep slow waves. These findings indicate that REM sleep is a spatially and temporally heterogeneous state and may contribute to explaining its known functional and phenomenological properties., (Copyright © 2019 the authors.)

Classical studies have isolated a distributed network of temporal and frontal areas engaged in the neural representation of speech perception and production. With modern literature arguing against unique roles for these cortical regions, different theories have favored either neural code-sharing or cortical space-sharing, thus trying to explain the intertwined spatial and functional organization of motor and acoustic components across the fronto-temporal cortical network. In this context, the focus of attention has recently shifted toward specific model fitting, aimed at motor and/or acoustic space reconstruction in brain activity within the language network. Here, we tested a model based on acoustic properties (formants), and one based on motor properties (articulation parameters), where model-free decoding of evoked fMRI activity during perception, imagery, and production of vowels had been successful. Results revealed that phonological information organizes around formant structure during the perception of vowels; interestingly, such a model was reconstructed in a broad temporal region, outside of the primary auditory cortex, but also in the pars triangularis of the left inferior frontal gyrus. Conversely, articulatory features were not associated with brain activity in these regions. Overall, our results call for a degree of interdependence based on acoustic information, between the frontal and temporal ends of the language network.

This article starts out with a summary of Weber's views on value freedom, by emphasizing: (1) that value freedom constitutes a special constellation of values; and (2) that value freedom makes it possible for the social scientist to theorize on the basis of new and more extensive knowledge than if she had simply stated her own values and focused the analysis around these. The latter point emerges most clearly in Weber's instructions for how a social scientist should proceed when carrying out an analysis of her own preferred social policy. After the section on Weber's views on value freedom, an attempt is made to update his views. This is done by arguing that the impact of values (and value freedom) differs, depending on where these can be found: on paper, in the head of the social scientist, or in her actions. "Actions," in the context of value freedom, refer to the research process and especially to the element of theorizing. Value freedom helps to guide the research into new and fruitful directions and to steer it clear of propaganda., (© 2017 Canadian Sociological Association/La Société canadienne de sociologie.)

Background: Nutrition and diet apps represent today a popular area of mobile health (mHealth), offering the possibility of delivering behavior change (BC) interventions for healthy eating and weight management in a scalable and cost-effective way. However, if commercial apps for pediatric weight management fail to retain users because of a lack of theoretical background and evidence-based content, mHealth apps that are more evidence-based are found less engaging and popular among consumers. Approaching the apps development process from a multidisciplinary and user-centered design (UCD) perspective is likely to help overcome these limitations, raising the chances for an easier adoption and integration of nutrition education apps within primary care interventions., Objective: The aim of this study was to describe the design and development of the TreC-LifeStyle nutrition education app and the results of a formative evaluation with families., Methods: The design of the nutrition education intervention was based on a multidisciplinary UCD approach, involving a team of BC experts, working with 2 nutritionists and 3 pediatricians from a primary care center. The app content was derived from evidence-based knowledge founded on the Food Pyramid and Mediterranean Diet guidelines used by pediatricians in primary care. A formative evaluation of the TreC-LifeStyle app involved 6 families of overweight children (aged 7-12 years) self-reporting daily food intake of children for 6 weeks and providing feedback on the user experience with the mHealth intervention. Analysis of the app's usage patterns during the intervention and of participants' feedback informed the refinement of the app design and a tuning of the nutrition education strategies to improve user engagement and compliance with the intervention., Results: Design sessions with the contribution of pediatricians and nutritionists helped define the nutrition education app and intervention, providing an effective human and virtual coaching approach to raise parents' awareness about children's eating behavior and lifestyle. The 6 families participating in the pilot study found the app usable and showed high compliance with the intervention over the 6 weeks, but analysis of their interaction and feedback showed the need for improving some of the app features related to the BC techniques "monitoring of the behavior" and "information provision.", Conclusions: The UCD and formative evaluation of TreC-LifeStyle show that nutrition education apps are feasible and acceptable solutions to support health promotion interventions in primary care., (©Silvia Gabrielli, Marco Dianti, Rosa Maimone, Marta Betta, Lorena Filippi, Monica Ghezzi, Stefano Forti. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 13.04.2017.)

Herpes zoster arises from reactivation of the varicella-zoster virus (VZV), causing varicella in children. As reactivation occurs when cell-mediated immunity (CMI) declines, and there is evidence that re-exposure to VZV boosts CMI, mass varicella immunization might increase the zoster burden, at least for some decades. Fear of this natural zoster boom is the main reason for the paralysis of varicella immunization in Europe. We apply optimal control to a realistically parametrized age-structured model for VZV transmission and reactivation to investigate whether feasible varicella immunization paths that are optimal in controlling both varicella and zoster exist. We analyse the optimality system numerically focusing on the role of the cost functional, of the relative zoster-varicella cost and of the planning horizon length. We show that optimal programmes will mostly be unfeasible for public health owing to their complex temporal profiles. This complexity is the consequence of the intrinsically antagonistic nature of varicella immunization programmes when aiming to control both varicella and zoster. However, we show that gradually increasing-hence feasible-vaccination schedules can perform better than routine programmes with constant vaccine uptake. Finally, we show the optimal profiles of feasible programmes targeting mitigation of the post-immunization natural zoster boom with priority., (© 2016 The Author(s).)

This paper describes the comparison between two drug control strategies to hemophilia A. To emulate blood clotting and the pathological condition of hemophilia, a mathematical model composed by 14 ordinary differential equations is considered. We adopt a variable structure non-linear PID approach and a Model Predictive Control in order to control the dosage of procoagulant factor used in the treatment of hemophiliac patient. The two control actions are sampled for a practical application. Finally, we discuss and compare the results of the two control approaches, introducing a suited control index (eINR).

Rapid eye movements (REMs) are a peculiar and intriguing aspect of REM sleep, even if their physiological function still remains unclear. During this work, a new automatic tool was developed, aimed at a complete description of REMs activity during the night, both in terms of their timing of occurrence that in term of their directional properties. A classification stage of each singular movement detected during the night according to its main direction, was in fact added to our procedure of REMs detection and ocular artifact removal. A supervised classifier was constructed, using as training and validation set EOG data recorded during voluntary saccades of five healthy volunteers. Different classification methods were tested and compared. The further information about REMs directional characteristic provided by the procedure would represent a valuable tool for a deeper investigation into REMs physiological origin and functional meaning.

This paper describes a simulation study which aims at optimizing the therapy for the control of Chronic Myeloid Leukemia according to the following objectives: the reduction of the administered drug and vaccine amounts, the establishment of a auto-immune response and the long-term control of disease without reducing the effective of therapy with respect to the full treatment. A therapy optimization method is developed defining and solving a Model Predictive Control algorithm, preceded by an accurate Initial Guess search based on Monte-Carlo like approach. Simulation results show that the suggested procedure achieves the proposed goals.

Rapid eye movements (REMs) are a prominent feature of REM sleep, and their distribution and time density over the night represent important physiological and clinical parameters. At the same time, REMs produce substantial distortions on the electroencephalographic (EEG) signals, which strongly affect the significance of normal REM sleep quantitative study. In this work a new procedure for a complete and automated analysis of REM sleep is proposed, which includes both a REMs detection algorithm and an ocular artifact removal system. The two steps, based respectively on Wavelet Transform and adaptive filtering, are fully integrated and their performance is evaluated using REM simulated signals. Thanks to the integration with the detection algorithm, the proposed artifact removal system shows an enhanced accuracy in the recovering of the true EEG signal, compared to a system based on the adaptive filtering only. Finally the artifact removal system is applied to physiological data and an estimation of the actual distortion induced by REMs on EEG signals is supplied.

Context and Objective: Despite the differences in the main characteristics between the autosomal dominant form of GH deficiency (IGHD II) and the bioinactive GH syndrome, a common feature of both is their impact on linear growth leading to short stature in all affected patients., Design: The index patient, a boy, was referred for assessment of his short stature (-2.54 SD score) and a delayed bone age of 5.9 yrs at the chronological age of 7.7 yrs. The GHD was confirmed by standard GH provocation tests, which revealed modestly reduced GH and IGF-I concentrations. Further genetic analysis of GH-1 gene identified heterozygosity for GH-P59L mutation. The secretion of the GH-P59L following stimulation with forskolin was investigated and compared to that of the wt-GH after expression of both GH variants in AtT-20 cells. Based on the position of P59L mutation that lies within a patch of residues composing the GH binding site 1 for GHR, we performed the analysis of GH-P59L binding to GHR by in silico mutagenesis and molecular dynamics simulations, which suggested possible problems in correct binding of GH-P59L to the GHR. Therefore, the functional characterization of this GH mutant was assessed through studies of GHR binding and activation of Jak2/Stat5 signaling pathway., Results: In line with the clinical data of the patient GH deficiency is suggested, underlined by GH-secretion studies revealing a moderate difference in secretion between GH-P59L and wt-GH. In addition, further functional characterization of the GH-P59L by studies of GH-receptor binding and activation of Jak2/Stat5 pathway presented with a reduced binding affinity of GH-P59L for GHR and decreased bioactivity compared to the wt-GH., Conclusions: The clinical data of the patient combined with the laboratory data support the diagnosis of partial IGHD type II. Since the GH deficiency was not total, additional binding and signaling studies were performed, which revealed that the GH-P59L variant displays some of the common features of bioinactive GH syndrome. Taken together, in this study we report a patient suffering from the combination of two growth disorders (alteration of secretion as well as bioactivity) caused by a GH-1 gene alteration highlighting the necessity of functional analysis of any GH variant, despite the presence of obvious clinical features of IGHD type II., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Increasingly the rapid developments by scientists working in the new business sector of biotechnology are being thrust into mainstream news reports. The incredible pace of the creation of neo-knowledge recently leads us to believe there has not been enough time between events for the healthcare sector, the general public, the legislators or the ethicists to reflect and conduct the checks and balances required for thoughtful progress. The decline of the hospital and the emergence of the laboratory as a consequence of the advent of the genomic era signal a profound shift, which will have unprecedented impacts on professionals in the healthcare system and its repercussions will force explicit changes in their education.