Identification of neuronal network properties from the spectral analysis of calcium imaging signals in neuronal cultures

Neuronal networks in vitro are prominent systems to study the development of connections in living neuronal networks and the interplay between connectivity, activity and function. These cultured networks show a rich spontaneous activity that evolves concurrently with the connectivity of the underlying network. In this work we monitor the development of neuronal cultures, and record their activity using calcium fluorescence imaging. We use spectral analysis to characterize global dynamical and structural traits of the neuronal cultures. We first observe that the power spectrum can be used as a signature of the state of the network, for instance when inhibition is active or silent, as well as a measure of the network's connectivity strength. Second, the power spectrum identifies prominent developmental changes in the network such as GABAA switch. And third, the analysis of the spatial distribution of the spectral density, in experiments with a controlled disintegration of the network through CNQX, an AMPA-glutamate receptor antagonist in excitatory neurons, reveals the existence of communities of strongly connected, highly active neurons that display synchronous oscillations. Our work illustrates the interest of spectral analysis for the study of in vitro networks, and its potential use as a network-state indicator, for instance to compare healthy and diseased neuronal networks.

Meta-analysis : subclinical thyroid dysfunction and the risk for coronary heart disease and mortality

Rapport de synthèse : Description : ce travail de thèse évalue de façon systématique les études sur l'association entre les dysfonctions thyroïdiennes infracliniques d'une part, et la maladie coronarienne et la mortalité d'autre part. Les hypothyroïdies infracliniques affectent environ 4-5% de la population adulte alors que la prévalence de l'hyperthyroïdie infraclinique est inférieure (environ 1%). L'éventuelle association entre elles pourrait justifier un dépistage systématique des dysfonctions thyroïdiennes infracliniques. Les précédentes études sur l'association entre l'hypothyroïdie infraclinique et la maladie coronarienne ont donné des résultats conflictuels. La parution de nouveaux articles récents basés sur de grandes cohortes prospectives nous a permis d'effectuer une méta-analyse basée uniquement sur des études de cohorte prospectives, augmentant ainsi la validité des résultats. Résultats: 10 des 12 études identifiées pour notre revue systématique sont basées sur des cohortes issues de la population générale («population-based »), regroupant en tout 14 449 participants. Ces 10 études examinent toutes le risque associé à l'hypothyroïdie infraclinique (avec 2134 événements coronariens et 2822 décès), alors que 5 étudient également le risque associé à l'hyperthyroïdie infraclinique (avec 1392 événements coronariens et 1993 décès). En utilisant un modèle statistique de type random-effect model, le risque relatif [RR] lié à l'hypothyroïdie infraclinique pour la maladie coronarienne est de 1.20 (intervalle de confiance [IC] de 95%, 0.97 à 1.49). Le risque diminue lorsque l'on regroupe uniquement les études de meilleure qualité (RR compris entre 1.02 et 1.08). Il est plus élevé parmi les participants de moins de 65 ans (RR, 1.51 [IC, 1.09 à 2.09] et 1.05 [IC, 0.90 à 1.22] pour les études dont l'âge moyen des participants est >_ 65 ans). Le RR de la mortalité cardiovasculaire est de 1.18 (IC, 0.98 à 1.42) et de 1.12 (IC, 0.99 à 1.26) pour la mortalité totale. En cas d'hyperthyroïdie infraclinique, les RR de la maladie coronarienne sont de 1.21 (IC, 0.88 à 1.68), de 1.19 (IC, 0.81 à 1.76) pour la mortalité cardiovasculaire, et de 1.12 (IC, 0.89 à 1.42) pour la mortalité totale. Conclusions et perspectives : nos résultats montrent que les dysfonctions thyroïdiennes infracliniques (hypothyroïdie et hyperthyroïdie infracliniques) représentent un facteur de risque modifiable, bien que modéré, de la maladie coronarienne et de la mortalité. L'efficacité du traitement de ces dysfonctions thyroïdiennes infracliniques doit encore être prouvée du point de vue cardiovasculaire et de la mortalité. Il est nécessaire d'effectuer des études contrôlées contre placebo avec le risque cardiovasculaire et la mortalité comme critères d'efficacité, avant de pouvoir proposer des recommandations sur le dépistage des ces dysfonctions thyroïdiennes dans la population adulte.

Effect of compression wood on surface roughness and surface absorption of medium density fiberboard

Abstract

Reconciling phonological neighborhood effects in speech production through single trial analysis

A crucial step for understanding how lexical knowledge is represented is to describe the relative similarity of lexical items, and how it influences language processing. Previous studies of the effects of form similarity on word production have reported conflicting results, notably within and across languages. The aim of the present study was to clarify this empirical issue to provide specific constraints for theoretical models of language production. We investigated the role of phonological neighborhood density in a large-scale picture naming experiment using fine-grained statistical models. The results showed that increasing phonological neighborhood density has a detrimental effect on naming latencies, and re-analyses of independently obtained data sets provide supplementary evidence for this effect. Finally, we reviewed a large body of evidence concerning phonological neighborhood density effects in word production, and discussed the occurrence of facilitatory and inhibitory effects in accuracy measures. The overall pattern shows that phonological neighborhood generates two opposite forces, one facilitatory and one inhibitory. In cases where speech production is disrupted (e.g. certain aphasic symptoms), the facilitatory component may emerge, but inhibitory processes dominate in efficient naming by healthy speakers. These findings are difficult to accommodate in terms of monitoring processes, but can be explained within interactive activation accounts combining phonological facilitation and lexical competition.

Bone mineral density (BMD), micro-architecture estimation (TBS) and vertebral fracture assessment (VFA) extracted from a single DXA device in combination with clinical risk factors improve significantly the identification of women at high risk of fracture.

Osteoporosis (OP) is a systemic skeletal disease characterized by a low bone mineral density (BMD) and a micro-architectural (MA) deterioration. Clinical risk factors (CRF) are often used as a MA approximation. MA is yet evaluable in daily practice by the trabecular bone score (TBS) measure. TBS is very simple to obtain, by reanalyzing a lumbar DXA-scan. TBS has proven to have diagnosis and prognosis values, partially independent of CRF and BMD. The aim of the OsteoLaus cohort is to combine in daily practice the CRF and the information given by DXA (BMD, TBS and vertebral fracture assessment (VFA)) to better identify women at high fracture risk. The OsteoLaus cohort (1400 women 50 to 80 years living in Lausanne, Switzerland) started in 2010. This study is derived from the cohort COLAUS who started in Lausanne in 2003. The main goal of COLAUS is to obtain information on the epidemiology and genetic determinants of cardiovascular risk in 6700 men and women. CRF for OP, bone ultrasound of the heel, lumbar spine and hip BMD, VFA by DXA and MA evaluation by TBS are recorded in OsteoLaus. Preliminary results are reported. We included 631 women: mean age 67.4 ± 6.7 years, BMI 26.1 ± 4.6, mean lumbar spine BMD 0.943 ± 0.168 (T-score − 1.4 SD), and TBS 1.271 ± 0.103. As expected, correlation between BMD and site matched TBS is low (r2 = 0.16). Prevalence of VFx grade 2/3, major OP Fx and all OP Fx is 8.4%, 17.0% and 26.0% respectively. Age- and BMI-adjusted ORs (per SD decrease) are 1.8 (1.2-2.5), 1.6 (1.2-2.1), and 1.3 (1.1-1.6) for BMD for the different categories of fractures and 2.0 (1.4-3.0), 1.9 (1.4-2.5), and 1.4 (1.1-1.7) for TBS respectively. Only 32 to 37% of women with OP Fx have a BMD < − 2.5 SD or a TBS < 1.200. If we combine a BMD < − 2.5 SD or a TBS < 1.200, 54 to 60% of women with an osteoporotic Fx are identified. As in the already published studies, these preliminary results confirm the partial independence between BMD and TBS. More importantly, a combination of TBS subsequent to BMD increases significantly the identification of women with prevalent OP Fx which would have been misclassified by BMD alone. For the first time we are able to have complementary information about fracture (VFA), density (BMD), micro- and macro architecture (TBS and HAS) from a simple, low ionizing radiation and cheap device: DXA. Such complementary information is very useful for the patient in the daily practice and moreover will likely have an impact on cost effectiveness analysis.

Coliform density in oyster culture waters and its relationship with environmental factors

The objective of this work was to evaluate the total and thermotolerant coliform densities in the oyster culture water of Cananeia, SP, Brazil, correlating these densities with environmental variables and tidal variations. Superficial water samples were collected in two tide conditions (spring and neap) from three areas of Cananéia municipality (Mandira, Itapitangui and Cooperostra). The three studied areas showed good conditions for the culture regarding coliform densities. The two tidal conditions differed significantly as to total coliform concentration; however, the same procedure was not performed for thermotolerant coliforms. No correlation was observed between water temperature, pH, and concentrations of total and thermotolerant coliforms. Coliform density was positively correlated with rainfall and negatively correlated with salinity. Spring and neap tides differed significantly as to coliform number. Simple diagnosis of environmental conditions of the crop fields is insufficient to assess water quality of shellfish cultivation. A continuous monitoring program of planted areas is necessary both for the assessment of water quality potential for marine culture and for ensuring safe consumption of seafood, besides constituting an important tool to understand the relationships between contamination and the involved environmental variables.

Facilitatory and interfering effects of neighbourhood density on speech production: Evidence from aphasic errors.

In a system where tens of thousands of words are made up of a limited number of phonemes, many words are bound to sound alike. This similarity of the words in the lexicon as characterized by phonological neighbourhood density (PhND) has been shown to affect speed and accuracy of word comprehension and production. Whereas there is a consensus about the interfering nature of neighbourhood effects in comprehension, the language production literature offers a more contradictory picture with mainly facilitatory but also interfering effects reported on word production. Here we report both of these two types of effects in the same study. Multiple regression mixed models analyses were conducted on PhND effects on errors produced in a naming task by a group of 21 participants with aphasia. These participants produced more formal errors (interfering effect) for words in dense phonological neighbourhoods, but produced fewer nonwords and semantic errors (a facilitatory effect) with increasing density. In order to investigate the nature of these opposite effects of PhND, we further analysed a subset of formal errors and nonword errors by distinguishing errors differing on a single phoneme from the target (corresponding to the definition of phonological neighbours) from those differing on two or more phonemes. This analysis confirmed that only formal errors that were phonological neighbours of the target increased in dense neighbourhoods, while all other errors decreased. Based on additional observations favouring a lexical origin of these formal errors (they exceeded the probability of producing a real-word error by chance, were of a higher frequency, and preserved the grammatical category of the targets), we suggest that the interfering effect of PhND is due to competition between lexical neighbours and target words in dense neighbourhoods.

Seasonality of cardiovascular risk factors: an analysis including over 230 000 participants in 15 countries.

OBJECTIVE: To assess the seasonality of cardiovascular risk factors (CVRF) in a large set of population-based studies. METHODS: Cross-sectional data from 24 population-based studies from 15 countries, with a total sample size of 237 979 subjects. CVRFs included Body Mass Index (BMI) and waist circumference; systolic (SBP) and diastolic (DBP) blood pressure; total, high (HDL) and low (LDL) density lipoprotein cholesterol; triglycerides and glucose levels. Within each study, all data were adjusted for age, gender and current smoking. For blood pressure, lipids and glucose levels, further adjustments on BMI and drug treatment were performed. RESULTS: In the Northern and Southern Hemispheres, CVRFs levels tended to be higher in winter and lower in summer months. These patterns were observed for most studies. In the Northern Hemisphere, the estimated seasonal variations were 0.26 kg/m(2) for BMI, 0.6 cm for waist circumference, 2.9 mm Hg for SBP, 1.4 mm Hg for DBP, 0.02 mmol/L for triglycerides, 0.10 mmol/L for total cholesterol, 0.01 mmol/L for HDL cholesterol, 0.11 mmol/L for LDL cholesterol, and 0.07 mmol/L for glycaemia. Similar results were obtained when the analysis was restricted to studies collecting fasting blood samples. Similar seasonal variations were found for most CVRFs in the Southern Hemisphere, with the exception of waist circumference, HDL, and LDL cholesterol. CONCLUSIONS: CVRFs show a seasonal pattern characterised by higher levels in winter, and lower levels in summer. This pattern could contribute to the seasonality of CV mortality.

Computational and Experimental Analysis of Flow Field in the Diffusers of Centrifugal Compressors

Centrifugal compressors are widely used for example in process industry, oil and gas industry, in small gas turbines and turbochargers. In order to achieve lower consumption of energy and operation costs the efficiency of the compressor needs to be improve. In the present work different pinches and low solidity vaned diffusers were utilized in order to improve the efficiency of a medium size centrifugal compressor. In this study, pinch means the decrement of the diffuser flow passage height. First different geometries were analyzed using computational fluid dynamics. The flow solver Finflo was used to solve the flow field. Finflo is a Navier-Stokes solver. The solver is capable to solve compressible, incompressible, steady and unsteady flow fields. Chien's k-e turbulence model was used. One of the numerically investigated pinched diffuser and one low solidity vaned diffuser were studied experimentally. The overall performance of the compressor and the static pressure distribution before and after the diffuser were measured. The flow entering and leaving the diffuser was measured using a three-hole Cobra-probe and Kiel-probes. The pinch and the low solidity vaned diffuser increased the efficiency of the compressor. Highest isentropic efficiency increment obtained was 3\% of the design isentropic efficiency of the original geometry. It was noticed in the numerical results that the pinch made to the hub and the shroud wall was most beneficial to the operation of the compressor. Also the pinch made to the hub was better than the pinchmade to the shroud. The pinch did not affect the operation range of the compressor, but the low solidity vaned diffuser slightly decreased the operation range.The unsteady phenomena in the vaneless diffuser were studied experimentally andnumerically. The unsteady static pressure was measured at the diffuser inlet and outlet, and time-accurate numerical simulation was conducted. The unsteady static pressure showed that most of the pressure variations lay at the passing frequency of every second blade. The pressure variations did not vanish in the diffuser and were visible at the diffuser outlet. However, the amplitude of the pressure variations decreased in the diffuser. The time-accurate calculations showed quite a good agreement with the measured data. Agreement was very good at the design operation point, even though the computational grid was not dense enough inthe volute and in the exit cone. The time-accurate calculation over-predicted the amplitude of the pressure variations at high flow.

Quantitative Ultrasound of the Heel and Fracture Risk Assessment: an Updated Meta-Analysis

Objectives: Quantitative ultrasound (QUS) is an attractive method for assessing fracture risk because it is portable, inexpensive, without ionizing radiation, and available in areas of the world where DXA is not readily accessible or affordable. However, the diversity of QUS scanners and variability of fracture outcomes measured in different studies is an important obstacle to widespread utilisation of QUS for fracture risk assessment. We aimed in this review to assess the predictive power of heel QUS for fractures considering different characteristics of the association (QUS parameters and fracture outcomes measured, QUS devices, study populations, and independence from DXA-measured bone density).Materials/Methods : We conducted an inverse-variance randomeffects meta-analysis of prospective studies with heel QUS measures at baseline and fracture outcomes in their follow-up. Relative risks (RR) per standard deviation (SD) of different QUS parameters (broadband ultrasound attenuation [BUA], speed of sound &SOS;, stiffness index &SI;, and quantitative ultrasound index [QUI]) for various fracture outcomes (hip, vertebral, any clinical, any osteoporotic, and major osteoporotic fractures) were reported based on study questions.Results : 21 studies including 55,164 women and 13,742 men were included with a total follow-up of 279,124 person-years. All four QUS parameters were associated with risk of different fractures. For instance, RR of hip fracture for 1 SD decrease of BUA was 1.69 (95% CI 1.43-2.00), SOS was 1.96 (95% CI 1.64-2.34), SI was 2.26 (95%CI 1.71-2.99), and QUI was 1.99 (95% CI 1.49-2.67). Validated devices from different manufacturers predicted fracture risks with a similar performance (meta-regression p-values>0.05 for difference of devices). There was no sign of publication bias among the studies. QUS measures predicted fracture with a similar performance in men and women. Meta-analysis of studies with QUS measures adjusted for hip DXA showed a significant and independent association with fracture risk (RR/SD for BUA =1.34 [95%CI 1.22-1.49]).Conclusions : This study confirms that QUS of the heel using validated devices predicts risk of different fracture outcomes in elderly men and women. Further research and international collaborations are needed for standardisation of QUS parameters across various manufacturers and inclusion of QUS in fracture risk assessment tools. Disclosure of Interest : None declared.

Meta-analysis and imputation refines the association of 15q25 with smoking quantity.

Smoking is a leading global cause of disease and mortality. We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (P = 9.45 x 10(-19)) that includes CHRNA5, CHRNA3 and CHRNB4, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref. 2) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of CHRNA5. Conditional analysis also identified a secondary locus (rs6495308) in CHRNA3.

RiskDiff: A web tool for the analysis of the difference due to risk and demographic factors for incidence or mortality data.

Background Analysing the observed differences for incidence or mortality of a particular disease between two different situations (such as time points, geographical areas, gender or other social characteristics) can be useful both for scientific or administrative purposes. From an epidemiological and public health point of view, it is of great interest to assess the effect of demographic factors in these observed differences in order to elucidate the effect of the risk of developing a disease or dying from it. The method proposed by Bashir and Estève, which splits the observed variation into three components: risk, population structure and population size is a common choice at practice. Results A web-based application, called RiskDiff has been implemented (available at http://rht.iconcologia.net/riskdiff.htm webcite), to perform this kind of statistical analyses, providing text and graphical summaries. Code from the implemented functions in R is also provided. An application to cancer mortality data from Catalonia is used for illustration. Conclusions Combining epidemiological with demographical factors is crucial for analysing incidence or mortality from a disease, especially if the population pyramids show substantial differences. The tool implemented may serve to promote and divulgate the use of this method to give advice for epidemiologic interpretation and decision making in public health.

Analysis of a finite volume method for a cross-diffusion model in population dynamics

The main goal of this paper is to propose a convergent finite volume method for a reactionâeuro"diffusion system with cross-diffusion. First, we sketch an existence proof for a class of cross-diffusion systems. Then the standard two-point finite volume fluxes are used in combination with a nonlinear positivity-preserving approximation of the cross-diffusion coefficients. Existence and uniqueness of the approximate solution are addressed, and it is also shown that the scheme converges to the corresponding weak solution for the studied model. Furthermore, we provide a stability analysis to study pattern-formation phenomena, and we perform two-dimensional numerical examples which exhibit formation of nonuniform spatial patterns. From the simulations it is also found that experimental rates of convergence are slightly below second order. The convergence proof uses two ingredients of interest for various applications, namely the discrete Sobolev embedding inequalities with general boundary conditions and a space-time $L^1$ compactness argument that mimics the compactness lemma due to Kruzhkov. The proofs of these results are given in the Appendix.

Heat Transfer Analysis of the EPR Core Catcher Test Facility Volley

Uusi EPR-reaktorikonsepti on suunniteltu selviytymään tapauksista, joissa reaktorinsydän sulaa ja sula puhkaisee paineastian. Suojarakennuksen sisälle on suunniteltu alue, jolle sula passiivisesti kerätään, pidätetään ja jäähdytetään. Alueelle laaditaan valurautaelementeistä ns.sydänsieppari, joka tulvitetaan vedellä. Sydänsulan tuottama jälkilämpö siirtyyveteen, mistä se poistetaan suojarakennuksen jälkilämmönpoistojärjestelmän kautta. Suuri osa lämmöstä poistuu sydänsulasta sen yläpuolella olevaan veteen, mutta lämmönsiirron tehostamiseksi myös sydänsiepparin alapuolelle on sijoitettu vedellä täytettävät jäähdytyskanavat. Jotta sydänsiepparin toiminta voitaisiin todentaa, on Lappeenrannan Teknillisellä Yliopistolla rakennettu Volley-koelaitteisto tätä tarkoitusta varten. Koelaitteisto koostuu kahdesta täysimittaisesta valuraudasta tehdystä jäähdytyskanavasta. Sydänsulan tuottamaa jälkilämpöä simuloidaan koelaitteistossa sähkövastuksilla. Tässä työssä kuvataan simulaatioiden suorittaminen ja vertaillaan saatuja arvoja mittaustuloksiin. Työ keskittyy sydänsiepparista jäähdytyskanaviin tapahtuvan lämmönsiirron teoriaan jamekanismeihin. Työssä esitetään kolme erilaista korrelaatiota lämmönsiirtokertoimille allaskiehumisen tapauksessa. Nämä korrelaatiot soveltuvat erityisesti tapauksiin, joissa vain muutamia mittausparametreja on tiedossa. Työn toinen osa onVolley 04 -kokeiden simulointi. Ensin käytettyä simulointitapaa on kelpoistettuvertaamalla tuloksia Volley 04 ja 05 -kokeisiin, joissa koetta voitiin jatkaa tasapainotilaan ja joissa jäähdytteen käyttäytyminen jäähdytyskanavassa on tallennettu myös videokameralla. Näiden simulaatioiden tulokset ovat hyvin samanlaisiakuin mittaustulokset. Korkeammilla lämmitystehoilla kokeissa esiintyi vesi-iskuja, jotka rikkoivat videoinnin mahdollistavia ikkunoita. Tämän johdosta osassa Volley 04 -kokeita ikkunat peitettiin metallilevyillä. Joitakin kokeita jouduttiin keskeyttämään laitteiston suurten lämpöjännitysten johdosta. Tällaisten testien simulaatiot eivät ole yksinkertaisia suorittaa. Veden pinnan korkeudesta ei ole visuaalista havaintoa. Myöskään jäähdytteen tasapainotilanlämpötiloista ei ole tarkkaa tietoa, mutta joitakin oletuksia voidaan tehdä samoilla parametreilla tehtyjen Volley 05 -kokeiden perusteella. Mittaustulokset Volley 04 ja 05 -kokeista, jotka on videoitu ja voitu ajaa tasapainotilaan saakka, antoivat simulaatioiden kanssa hyvin samankaltaisia lämpötilojen arvoja. Keskeytettyjen kokeiden ekstrapolointi tasapainotilaan ei onnistunut kovin hyvin. Kokeet jouduttiin keskeyttämään niin paljon ennen termohydraulista tasapainoa, ettei tasapainotilan reunaehtoja voitu ennustaa. Videonauhoituksen puuttuessa ei veden pinnan korkeudesta saatu lisätietoa. Tuloksista voidaan lähinnä esittää arvioita siitä, mitä suuruusluokkaa mittapisteiden lämpötilat tulevat olemaan. Nämä lämpötilat ovat kuitenkin selvästi alle sydänsiepparissa käytettävän valuraudan sulamislämpötilan. Joten simulaatioiden perusteella voidaan sanoa, etteivät jäähdytyskanavien rakenteet sula, mikäli niissä on pienikin jäähdytevirtaus, eikä useampia kuin muutama vierekkäinen kanava ole täysin kuivana.

Colloid cysts of the third ventricle: correlation of MR and CT findings with histology and chemical analysis.

Eight patients with colloid cysts of the third ventricle were examined with CT and MR. In six, surgical resection was performed and the material was subjected to histologic evaluation; the concentrations of trace elements were determined by particle-induced X-ray emission. Stereotaxic aspiration was performed in two. The investigation showed that colloid cysts are often iso- or hypodense relative to brain on CT (5/8), but sometimes have a center of increased density. Increased density did not correlate with increased concentration of calcium or other metals but did not correlate with high cholesterol content. Colloid cysts appear more heterogeneous on MR (6/8) than on CT (3/8), despite a homogeneous appearance at histology. High signal on short TR/TE sequences is correlated with a high cholesterol content. A marked shortening of the T2 relaxation time is often noticed in the central part of the cyst. Analysis of trace elements showed that this phenomenon is not related to the presence of metals with paramagnetic effects. Our analysis of the contents of colloid cysts does not support the theory that differing metallic concentrations are responsible for differences in MR signal intensity or CT density. We did find that increased CT density and high MR signal correlated with high cholesterol content.