Decoding sequence learning from single-trial intracranial EEG in humans.

We propose and validate a multivariate classification algorithm for characterizing changes in human intracranial electroencephalographic data (iEEG) after learning motor sequences. The algorithm is based on a Hidden Markov Model (HMM) that captures spatio-temporal properties of the iEEG at the level of single trials. Continuous intracranial iEEG was acquired during two sessions (one before and one after a night of sleep) in two patients with depth electrodes implanted in several brain areas. They performed a visuomotor sequence (serial reaction time task, SRTT) using the fingers of their non-dominant hand. Our results show that the decoding algorithm correctly classified single iEEG trials from the trained sequence as belonging to either the initial training phase (day 1, before sleep) or a later consolidated phase (day 2, after sleep), whereas it failed to do so for trials belonging to a control condition (pseudo-random sequence). Accurate single-trial classification was achieved by taking advantage of the distributed pattern of neural activity. However, across all the contacts the hippocampus contributed most significantly to the classification accuracy for both patients, and one fronto-striatal contact for one patient. Together, these human intracranial findings demonstrate that a multivariate decoding approach can detect learning-related changes at the level of single-trial iEEG. Because it allows an unbiased identification of brain sites contributing to a behavioral effect (or experimental condition) at the level of single subject, this approach could be usefully applied to assess the neural correlates of other complex cognitive functions in patients implanted with multiple electrodes.

Long-term outcome of preterm infants treated with nasal continuous positive airway pressure

RESUME La ventilation en pression positive continue (Continuous Positive Airway Pressure, CPAP), utilisée pour la première fois chez. les prématurés en 1971, est une technique actuellement très largement utilisée dans les unités néonatales. L'utilisation de la CPAP présente de nombreux avantages à court terme: diminution de la fraction maximale inspirée d'oxygène, de la durée de l'oxygénothérapie, du taux d'intubation et donc du recours à une ventilation mécanique, réduction de l'utilisation des amines, des curares et de la morphine, possible prévention de l'apparition d'une bronchodysplasie pulmonaire, et possibles réductions du nombre d'infections postnatales et des entérocolites nécrosantes. Mais peu d'études existent concernant les effets à long terme de la CPAP sur le neurodéveloppement et la croissance, qui constituent l'objectif de la présente étude. L'utilisation systématique de la CPAP comme alternative à la ventilation mécanique a été introduite à Lausanne en 1998. La population cible de cette étude est constituée des prématurés nés à moins de 32 semaines de gestation ou pesant moins de 1500 g à la naissance; ils ont été systématiquement suivis jusqu'en âge préscolaire dans le cadre de l'étude de cohorte «Unité de Développement, CHUV». L'originalité de ce travail réside dans le fait d'évaluer le neurodéveloppement et la croissance à long terme d'enfants prématurés traités préférentiellement avec la CPAP, en comparaison avec un groupe historique contrôle traité par d'autres modes ventilatoires, en tenant compte de nombreux autres paramètres néonataux. Du point de vue du neurodéveloppement, l'usage, de la CPAP montre une tendance à diminuer l'incidence d'hémorragie intraventriculaire et le risque d'avoir un mauvais neurodéveloppement à 6 mois. Ces résultats positifs sur le neurodéveloppement s'estompent à l'âge de 18 mois, où persiste néanmoins une valeur plus élevée du quotient de développement, et disparaissent complètement en âge préscolaire. Du point de vue de la croissance, l'utilisation de la CPAP ne montre aucun effet sur le poids, mais par contre un effet positif sur la taille à 6 et 18 mois et sur le périmètre crânien à 6 mois, 18 mois et en âge préscolaire. Malgré le caractère non randomisé de cette étude, les résultats positifs obtenus ici permettent sans conteste de s'assurer d'une utilisation de la CPAP sans effet négatif sur le neurodéveloppement et la croissance, et fournissent donc un argument supplémentaire pour l'utilisation systématique de la CPAP chez les prématurés.

Continuous versus single bolus enteral nutrition: comparison of energy metabolism in humans.

Continuous respiratory exchange measurements were performed on five women and five men for 1 h before and 6 h after the administration of a milkshake (53% carbohydrates, 30% lipid, and 17% protein energy) given either as a single bolus dose or continuously during 3 h using a nasogastric tube. The energy administered corresponded to 2.3 times the postabsorptive resting energy expenditure. Resting energy expenditure, respiratory quotient, plasma glucose, and insulin concentrations increased sooner and steeper, and plasma free fatty acids levels decreased earlier with the meal ingested as a single dose than with continuous administration. The magnitude of nutrient-induced thermogenesis was greater (P less than 0.01) with the single dose (means +/- SE, 10.0 +/- 0.6%) than with the continuous administration (8.1 +/- 0.5%). The overall (6 h) substrate balances were not significantly different between the two modes of administration. It is concluded that the mode of enteral nutrient administration influences the immediate thermogenic response as well as changes in respiratory quotient, glycemia, and insulinemia; however, the overall nutrient balance was not affected by the mode of enteral nutrient administration.

Combining molecular evolution and environmental genomics to unravel adaptive processes of MHC class IIB diversity in European minnows (Phoxinus phoxinus)

Host-pathogen interactions are a major evolutionary force promoting local adaptation. Genes of the major histocompatibility complex (MHC) represent unique candidates to investigate evolutionary processes driving local adaptation to parasite communities. The present study aimed at identifying the relative roles of neutral and adaptive processes driving the evolution of MHC class IIB (MHCIIB) genes in natural populations of European minnows (Phoxinus phoxinus). To this end, we isolated and genotyped exon 2 of two MHCIIB gene duplicates (DAB1 and DAB3) and 1665 amplified fragment length polymorphism (AFLP) markers in nine populations, and characterized local bacterial communities by 16S rDNA barcoding using 454 amplicon sequencing. Both MHCIIB loci exhibited signs of historical balancing selection. Whereas genetic differentiation exceeded that of neutral markers at both loci, the populations' genetic diversities were positively correlated with local pathogen diversities only at DAB3. Overall, our results suggest pathogen-mediated local adaptation in European minnows at both MHCIIB loci. While at DAB1 selection appears to favor different alleles among populations, this is only partially the case in DAB3, which appears to be locally adapted to pathogen communities in terms of genetic diversity. These results provide new insights into the importance of host-pathogen interactions in driving local adaptation in the European minnow, and highlight that the importance of adaptive processes driving MHCIIB gene evolution may differ among duplicates within species, presumably as a consequence of alternative selective regimes or different genomic context.

Epuration extrarénale continue pour l'insuffisance rénale aiguë aux soins intensifs [Continuous renal replacement therapy for acute kidney injury].

Acute kidney injury is common in critical illness and associated with important morbidity and mortality. Continuous renal replacement therapy (CRRT) enables physicians to safely and efficiently control associated metabolic and fluid balance disorders. The insertion of a large central venous catheter is required, which can be associated with mechanical and infectious complications. CRRT requires anticoagulation, which currently relies on heparin in most cases although citrate could become a standard in a near future. The choice of the substitution fluid depends on the clinical situation. A dose of 25 ml/kg/h is currently recommended.

Testing new identity models and processes in French-speaking adolescents and emerging adults students

Developing a sense of identity is a crucial psychosocial task for young people. The purpose of this study was to evaluate identity development in French-speaking adolescents and emerging adults (in France and Switzerland) using a process-oriented model of identity formation including five dimensions (i.e., exploration in breadth, commitment making, exploration in depth, identification with commitment, and ruminative exploration). The study included participants from three different samples (total N = 2239, 66.7% women): two samples of emerging adult student and one sample of adolescents. Results confirmed the hypothesized five-factor dimensional model of identity in our three samples and provided evidence for convergent validity of the model. The results also indicated that exploration in depth might be subdivided in two aspects: a first form of exploration in depth leading to a better understanding and to an increase of the strength of current commitments and a second form of exploration in depth leading to a re-evaluation and a reconsideration of current commitments. Further, the identity status cluster solution that emerged is globally in line with previous literature (i.e., achievement, foreclosure, moratorium, carefree diffusion, diffused diffusion, undifferentiated). However, despite a structural similarity, we found variations in identity profiles because identity development is shaped by cultural context. These specific variations are discussed in light of social, educational and economic differences between France and the French-speaking part of Switzerland. Implications and suggestions for future research are offered.

Three essays in control, entrepreneurship and innovation

One of the key emphases of these three essays is to provide practical managerial insight. However, good practical insight, can only be created by grounding it firmly on theoretical and empirical research. Practical experience-based understanding without theoretical grounding remains tacit and cannot be easily disseminated. Theoretical understanding without links to real life remains sterile. My studies aim to increase the understanding of how radical innovation could be generated at large established firms and how it can have an impact on business performance as most businesses pursue innovation with one prime objective: value creation. My studies focus on large established firms with sales revenue exceeding USD $ 1 billion. Usually large established firms cannot rely on informal ways of management, as these firms tend to be multinational businesses operating with subsidiaries, offices, or production facilities in more than one country. I. Internal and External Determinants of Corporate Venture Capital Investment The goal of this chapter is to focus on CVC as one of the mechanisms available for established firms to source new ideas that can be exploited. We explore the internal and external determinants under which established firms engage in CVC to source new knowledge through investment in startups. We attempt to make scholars and managers aware of the forces that influence CVC activity by providing findings and insights to facilitate the strategic management of CVC. There are research opportunities to further understand the CVC phenomenon. Why do companies engage in CVC? What motivates them to continue "playing the game" and keep their active CVC investment status. The study examines CVC investment activity, and the importance of understanding the influential factors that make a firm decide to engage in CVC. The main question is: How do established firms' CVC programs adapt to changing internal conditions and external environments. Adaptation typically involves learning from exploratory endeavors, which enable companies to transform the ways they compete (Guth & Ginsberg, 1990). Our study extends the current stream of research on CVC. It aims to contribute to the literature by providing an extensive comparison of internal and external determinants leading to CVC investment activity. To our knowledge, this is the first study to examine the influence of internal and external determinants on CVC activity throughout specific expansion and contraction periods determined by structural breaks occurring between 1985 to 2008. Our econometric analysis indicates a strong and significant positive association between CVC activity and R&D, cash flow availability and environmental financial market conditions, as well as a significant negative association between sales growth and the decision to engage into CVC. The analysis of this study reveals that CVC investment is highly volatile, as demonstrated by dramatic fluctuations in CVC investment activity over the past decades. When analyzing the overall cyclical CVC period from 1985 to 2008 the results of our study suggest that CVC activity has a pattern influenced by financial factors such as the level of R&D, free cash flow, lack of sales growth, and external conditions of the economy, with the NASDAQ price index as the most significant variable influencing CVC during this period. II. Contribution of CVC and its Interaction with R&D to Value Creation The second essay takes into account the demands of corporate executives and shareholders regarding business performance and value creation justifications for investments in innovation. Billions of dollars are invested in CVC and R&D. However there is little evidence that CVC and its interaction with R&D create value. Firms operating in dynamic business sectors seek to innovate to create the value demanded by changing market conditions, consumer preferences, and competitive offerings. Consequently, firms operating in such business sectors put a premium on finding new, sustainable and competitive value propositions. CVC and R&D can help them in this challenge. Dushnitsky and Lenox (2006) presented evidence that CVC investment is associated with value creation. However, studies have shown that the most innovative firms do not necessarily benefit from innovation. For instance Oyon (2007) indicated that between 1995 and 2005 the most innovative automotive companies did not obtain adequate rewards for shareholders. The interaction between CVC and R&D has generated much debate in the CVC literature. Some researchers see them as substitutes suggesting that firms have to choose between CVC and R&D (Hellmann, 2002), while others expect them to be complementary (Chesbrough & Tucci, 2004). This study explores the interaction that CVC and R&D have on value creation. This essay examines the impact of CVC and R&D on value creation over sixteen years across six business sectors and different geographical regions. Our findings suggest that the effect of CVC and its interaction with R&D on value creation is positive and significant. In dynamic business sectors technologies rapidly relinquish obsolete, consequently firms operating in such business sectors need to continuously develop new sources of value creation (Eisenhardt & Martin, 2000; Qualls, Olshavsky, & Michaels, 1981). We conclude that in order to impact value creation, firms operating in business sectors such as Engineering & Business Services, and Information Communication & Technology ought to consider CVC as a vital element of their innovation strategy. Moreover, regarding the CVC and R&D interaction effect, our findings suggest that R&D and CVC are complementary to value creation hence firms in certain business sectors can be better off supporting both R&D and CVC simultaneously to increase the probability of generating value creation. III. MCS and Organizational Structures for Radical Innovation Incremental innovation is necessary for continuous improvement but it does not provide a sustainable permanent source of competitiveness (Cooper, 2003). On the other hand, radical innovation pursuing new technologies and new market frontiers can generate new platforms for growth providing firms with competitive advantages and high economic margin rents (Duchesneau et al., 1979; Markides & Geroski, 2005; O'Connor & DeMartino, 2006; Utterback, 1994). Interestingly, not all companies distinguish between incremental and radical innovation, and more importantly firms that manage innovation through a one-sizefits- all process can almost guarantee a sub-optimization of certain systems and resources (Davila et al., 2006). Moreover, we conducted research on the utilization of MCS along with radical innovation and flexible organizational structures as these have been associated with firm growth (Cooper, 2003; Davila & Foster, 2005, 2007; Markides & Geroski, 2005; O'Connor & DeMartino, 2006). Davila et al. (2009) identified research opportunities for innovation management and provided a list of pending issues: How do companies manage the process of radical and incremental innovation? What are the performance measures companies use to manage radical ideas and how do they select them? The fundamental objective of this paper is to address the following research question: What are the processes, MCS, and organizational structures for generating radical innovation? Moreover, in recent years, research on innovation management has been conducted mainly at either the firm level (Birkinshaw, Hamel, & Mol, 2008a) or at the project level examining appropriate management techniques associated with high levels of uncertainty (Burgelman & Sayles, 1988; Dougherty & Heller, 1994; Jelinek & Schoonhoven, 1993; Kanter, North, Bernstein, & Williamson, 1990; Leifer et al., 2000). Therefore, we embarked on a novel process-related research framework to observe the process stages, MCS, and organizational structures that can generate radical innovation. This article is based on a case study at Alcan Engineered Products, a division of a multinational company provider of lightweight material solutions. Our observations suggest that incremental and radical innovation should be managed through different processes, MCS and organizational structures that ought to be activated and adapted contingent to the type of innovation that is being pursued (i.e. incremental or radical innovation). More importantly, we conclude that radical can be generated in a systematic way through enablers such as processes, MCS, and organizational structures. This is in line with the findings of Jelinek and Schoonhoven (1993) and Davila et al. (2006; 2007) who show that innovative firms have institutionalized mechanisms, arguing that radical innovation cannot occur in an organic environment where flexibility and consensus are the main managerial mechanisms. They rather argue that radical innovation requires a clear organizational structure and formal MCS.

Continuous electroencephalography in the medical intensive care unit.

OBJECTIVES: To examine predictors and the prognostic value of electrographic seizures (ESZs) and periodic epileptiform discharges (PEDs) in medical intensive care unit (MICU) patients without a primary acute neurologic condition. DESIGN: Retrospective study. SETTING: MICU in a university hospital. PATIENTS: A total of 201 consecutive patients admitted to the MICU between July 2004 and January 2007 without known acute neurologic injury and who underwent continuous electroencephalography monitoring (cEEG) for investigation of possible seizures or changes in mental status. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Median time from intensive care unit (ICU) admission to cEEG was 1 day (interquartile range 1-4). The majority of patients (60%) had sepsis as the primary admission diagnosis and 48% were comatose at the time of cEEG. Ten percent (n = 21) of patients had ESZs, 17% (n = 34) had PEDs, 5% (n = 10) had both, and 22% (n = 45) had either ESZs or PEDs. Seizures during cEEG were purely electrographic (no detectable clinical correlate) in the majority (67%) of patients. Patients with sepsis had a higher rate of ESZs or PEDs than those without sepsis (32% vs. 9%, p < 0.001). On multivariable analysis, sepsis at ICU admission was the only significant predictor of ESZs or PEDs (odds ratio 4.6, 95% confidence interval 1.9-12.7, p = 0.002). After controlling for age, coma, and organ dysfunction, the presence of ESZs or PEDs was associated with death or severe disability at hospital discharge (89% with ESZs or PEDs, vs. 39% if not; odds ratio 19.1, 95% confidence interval 6.3-74.6, p < 0.001). CONCLUSION: In this retrospective study of MICU patients monitored with cEEG, ESZs and PEDs were frequent, predominantly in patients with sepsis. Seizures were mainly nonconvulsive. Both seizures and periodic discharges were associated with poor outcome. Prospective studies are warranted to determine more precisely the frequency and clinical impact of nonconvulsive seizures and periodic discharges, particularly in septic patients.

Nocturnal hypoglycaemias in type 1 diabetic patients: what can we learn with continuous glucose monitoring?

AIM: In type 1 diabetic patients (T1DM), nocturnal hypoglycaemias (NH) are a serious complication of T1DM treatment; self-monitoring of blood glucose (SMBG) is recommended to detect them. However, the majority of NH remains undetected on an occasional SMBG done during the night. An alternative strategy is the Continuous glucose monitoring (CGMS), which retrospectively shows the glycaemic profile. The aims of this retrospective study were to evaluate the true incidence of NH in T1DM, the best SMBG time to predict NH, the relationship between morning hyperglycaemia and NH (Somogyi phenomenon) and the utility of CGMS to reduce NH. METHODS: Eighty-eight T1DM who underwent a CGMS exam were included. Indications for CGMS evaluation, hypoglycaemias and correlation with morning hyperglycaemias were recorded. The efficiency of CGMS to reduce the suspected NH was evaluated after 6-9 months. RESULTS: The prevalence of NH was 67% (32% of them unsuspected). A measured hypoglycaemia at bedtime (22-24 h) had a sensitivity of 37% to detect NH (OR=2.37, P=0.001), while a single measure < or =4 mmol/l at 3-hour had a sensitivity of 43% (OR=4.60, P<0.001). NH were not associated with morning hyperglycaemias but with morning hypoglycaemias (OR=3.95, P<0.001). After 6-9 months, suspicions of NH decreased from 60 to 14% (P<0.001). CONCLUSION: NH were highly prevalent and often undetected. SMBG at bedtime, which detected hypoglycaemia had sensitivity almost equal to that of 3-hour and should be preferred because it is easier to perform. Somogyi phenomenon was not observed. CGMS is useful to reduce the risk of NH in 75% of patients.

The brain uses single-trial multisensory memories to discriminate without awareness.

Multisensory experiences enhance perceptions and facilitate memory retrieval processes, even when only unisensory information is available for accessing such memories. Using fMRI, we identified human brain regions involved in discriminating visual stimuli according to past multisensory vs. unisensory experiences. Subjects performed a completely orthogonal task, discriminating repeated from initial image presentations intermixed within a continuous recognition task. Half of initial presentations were multisensory, and all repetitions were exclusively visual. Despite only single-trial exposures to initial image presentations, accuracy in indicating image repetitions was significantly improved by past auditory-visual multisensory experiences over images only encountered visually. Similarly, regions within the lateral-occipital complex-areas typically associated with visual object recognition processes-were more active to visual stimuli with multisensory than unisensory pasts. Additional differential responses were observed in the anterior cingulate and frontal cortices. Multisensory experiences are registered by the brain even when of no immediate behavioral relevance and can be used to categorize memories. These data reveal the functional efficacy of multisensory processing.

PyRate: a new program to estimate speciation and extinction rates from incomplete fossil data

Despite the advancement of phylogenetic methods to estimate speciation and extinction rates, their power can be limited under variable rates, in particular for clades with high extinction rates and small number of extant species. Fossil data can provide a powerful alternative source of information to investigate diversification processes. Here, we present PyRate, a computer program to estimate speciation and extinction rates and their temporal dynamics from fossil occurrence data. The rates are inferred in a Bayesian framework and are comparable to those estimated from phylogenetic trees. We describe how PyRate can be used to explore different models of diversification. In addition to the diversification rates, it provides estimates of the parameters of the preservation process (fossilization and sampling) and the times of speciation and extinction of each species in the data set. Moreover, we develop a new birth-death model to correlate the variation of speciation/extinction rates with changes of a continuous trait. Finally, we demonstrate the use of Bayes factors for model selection and show how the posterior estimates of a PyRate analysis can be used to generate calibration densities for Bayesian molecular clock analysis. PyRate is an open-source command-line Python program available at http://sourceforge.net/projects/pyrate/.

Unravelling the enigmatic origin of calcitic nanofibres in soils and caves: purely physicochemical or biogenic processes?

Calcitic nanofibres are ubiquitous habits of sec- ondary calcium carbonate (CaCO3 ) accumulations observed in calcareous vadose environments. Despite their widespread occurrence, the origin of these nanofeatures remains enig- matic. Three possible mechanisms fuel the debate: (i) purely physicochemical processes, (ii) mineralization of rod-shaped bacteria, and (iii) crystal precipitation on organic templates. Nanofibres can be either mineral (calcitic) or organic in na- ture. They are very often observed in association with needle fibre calcite (NFC), another typical secondary CaCO3 habit in terrestrial environments. This association has contributed to some confusion between both habits, however they are truly two distinct calcitic features and their recurrent asso- ciation is likely to be an important fact to help understanding the origin of nanofibres. In this paper the different hypotheses that currently exist to explain the origin of calcitic nanofibres are critically reviewed. In addition to this, a new hypothe- sis for the origin of nanofibres is proposed based on the fact that current knowledge attributes a fungal origin to NFC. As this feature and nanofibres are recurrently observed together, a possible fungal origin for nanofibres which are associated with NFC is investigated. Sequential enzymatic digestion of the fungal cell wall of selected fungal species demonstrates that the fungal cell wall can be a source of organic nanofibres. The obtained organic nanofibres show a striking morpho- logical resemblance when compared to their natural coun- terparts, emphasizing a fungal origin for part of the organic nanofibres observed in association with NFC. It is further hy- pothesized that these organic nanofibres may act as templates for calcite nucleation in a biologically influenced mineraliza- tion process, generating calcitic nanofibres. This highlights the possible involvement of fungi in CaCO3 biomineraliza- tion processes, a role still poorly documented. Moreover, on a global scale, the organomineralization of organic nanofi- bres into calcitic nanofibres might be an overlooked process deserving more attention to specify its impact on the biogeo- chemical cycles of both Ca and C.