Multiparametric brainstem segmentation using a modified multivariate mixture of Gaussians

The human brainstem is a densely packed, complex but highly organised structure. It not only serves as a conduit for long projecting axons conveying motor and sensory information, but also is the location of multiple primary nuclei that control or modulate a vast array of functions, including homeostasis, consciousness, locomotion, and reflexive and emotive behaviours. Despite its importance, both in understanding normal brain function as well as neurodegenerative processes, it remains a sparsely studied structure in the neuroimaging literature. In part, this is due to the difficulties in imaging the internal architecture of the brainstem in vivo in a reliable and repeatable fashion. A modified multivariate mixture of Gaussians (mmMoG) was applied to the problem of multichannel tissue segmentation. By using quantitative magnetisation transfer and proton density maps acquired at 3 T with 0.8 mm isotropic resolution, tissue probability maps for four distinct tissue classes within the human brainstem were created. These were compared against an ex vivo fixated human brain, imaged at 0.5 mm, with excellent anatomical correspondence. These probability maps were used within SPM8 to create accurate individual subject segmentations, which were then used for further quantitative analysis. As an example, brainstem asymmetries were assessed across 34 right-handed individuals using voxel based morphometry (VBM) and tensor based morphometry (TBM), demonstrating highly significant differences within localised regions that corresponded to motor and vocalisation networks. This method may have important implications for future research into MRI biomarkers of pre-clinical neurodegenerative diseases such as Parkinson's disease.

The role of role uncertainty in modified dictator games

We compare behavior in modified dictator games with and without role uncertainty. Subjectschoose between a selfish action, a costly surplus creating action (altruistic behavior) and acostly surplus destroying action (spiteful behavior). While costly surplus creating actions are themost frequent under role uncertainty (64%), selfish actions become the most frequent withoutrole uncertainty (69%). Also, the frequency of surplus destroying choices is negligible with roleuncertainty (1%) but not so without it (11%). A classification of subjects into four differenttypes of interdependent preferences (Selfish, Social Welfare maximizing, Inequity Averse andCompetitive) shows that the use of role uncertainty overestimates the prevalence of SocialWelfare maximizing preferences in the subject population (from 74% with role uncertainty to21% without it) and underestimates Selfish and Inequity Averse preferences. An additionaltreatment, in which subjects undertake an understanding test before participating in theexperiment with role uncertainty, shows that the vast majority of subjects (93%) correctlyunderstand the payoff mechanism with role uncertainty, but yet surplus creating actions weremost frequent. Our results warn against the use of role uncertainty in experiments that aim tomeasure the prevalence of interdependent preferences.

Elicited beliefs and social information in modified dictator games: What do dictators believe other dictators do?

We use subjects actions in modified dictator games to perform a within-subject classification ofindividuals into four different types of interdependent preferences: Selfish, Social Welfaremaximizers, Inequity Averse and Competitive. We elicit beliefs about other subjects actions inthe same modified dictator games to test how much of the existent heterogeneity in others actions is known by subjects. We find that subjects with different interdependent preferences infact have different beliefs about others actions. In particular, Selfish individuals cannotconceive others being non-Selfish while Social Welfare maximizers are closest to the actualdistribution of others actions. We finally provide subjects with information on other subjects actions and re-classify individuals according to their (new) actions in the same modified dictatorgames. We find that social information does not affect Selfish individuals, but that individualswith interdependent preferences are more likely to change their behavior and tend to behavemore selfishly.

Comparison of the diagnostic performance of the original and modified Wells score in inpatients and outpatients with suspected deep vein thrombosis.

Introduction: The original and modified Wells score are widely used prediction rules for pre-test probability assessment of deep vein thrombosis (DVT). The objective of this study was to compare the predictive performance of both Wells scores in unselected patients with clinical suspicion of DVT.Methods: Consecutive inpatients and outpatients with a clinical suspicion of DVT were prospectively enrolled. Pre-test DVT probability (low/intermediate/high) was determined using both scores. Patients with a non-high probability based on the original Wells score underwent D-dimers measurement. Patients with D-dimers <500 mu g/L did not undergo further testing, and treatment was withheld. All others underwent complete lower limb compression ultrasound, and those diagnosed with DVT were anticoagulated. The primary study outcome was objectively confirmed symptomatic venous thromboembolism within 3 months of enrollment.Results: 298 patients with suspected DVT were included. Of these, 82 (27.5%) had DVT, and 46 of them were proximal. Compared to the modified score, the original Wells score classified a higher proportion of patients as low-risk (53 vs 48%; p<0.01) and a lower proportion as high-risk (17 vs 15%; p=0.02); the prevalence of proximal DVT in each category was similar with both scores (7-8% low, 16-19% intermediate, 36-37% high). The area under the receiver operating characteristic curve regarding proximal DVT detection was similar for both scores, but they both performed poorly in predicting isolated distal DVT and DVT in inpatients.Conclusion: The study demonstrates that both Wells scores perform equally well in proximal DVT pre-test probability prediction. Neither score appears to be particularly useful in hospitalized patients and those with isolated distal DVT. (C) 2011 Elsevier Ltd. All rights reserved.

Nyssomyia intermedia (Lutz & Neiva) and Nyssomyia neivai (Pinto) (Diptera, Psychodidae, Phlebotominae) in a sympatric area: seasonal and nocturnal hourly rhythm in black and white modified Shannon traps

Captures with black and white Shannon traps were undertaken to identify aspects of the behavior of the two cryptic and sympatric species implicated as vectors of cutaneous leishmaniasis, Nyssomyia intermedia (Lutz & Neiva, 1912) and Nyssomyia neivai (Pinto, 1926). The traps were installed side by side, monthly, from July 2001 to June 2002, from 18 to 07 hours, in a peridomicile of Iporanga municipality, state of São Paulo, Brazil. A total of 2,142 specimens were captured, Ny. intermedia (47.4%) and Ny. neivai (50.5%). The white trap was more attractive to both sexes of both species. Males of Ny. neivai predominated (70%) over those of Ny. intermedia on the two traps; on the black trap, the females of Ny. intermedia predominated (63.3%) over those of Ny. neivai (36.7%). Seventy percent of the specimens of both species were captured between 18 and 24 h. Females of Ny. intermedia presented the highest peak at 19-20 h, and those of Ny. neivai at 20-21 h. The highest hourly average for females of Ny. intermedia on the black trap occurred in the winter and that for males in the summer. For Ny. neivai, both sexes predominated in the summer. The two species probably transmit the cutaneous leishmaniasis in the area due to their great predominance.

Programació d'una aplicació gràfica per l'anàlisi de senyals usant LDB (Local Discriminant Bases) i MLDB (Modified LDB)

Tot seguit presentem un entorn per analitzar senyals de tot tipus amb LDB (Local Discriminant Bases) i MLDB (Modified Local Discriminant Bases). Aquest entorn utilitza funcions desenvolupades en el marc d’una tesi en fase de desenvolupament. Per entendre part d’aquestes funcions es requereix un nivell de coneixement avançat de processament de senyals. S’han extret dels treballs realitzats per Naoki Saito [3], que s’han agafat com a punt de partida per la realització de l’algorisme de la tesi doctoral no finalitzada de Jose Antonio Soria. Aquesta interfície desenvolupada accepta la incorporació de nous paquets i funcions. Hem deixat un menú preparat per integrar Sinus IV packet transform i Cosine IV packet transform, tot i que també podem incorporar-n’hi altres. L’aplicació consta de dues interfícies, un Assistent i una interfície principal. També hem creat una finestra per importar i exportar les variables desitjades a diferents entorns. Per fer aquesta aplicació s’han programat tots els elements de les finestres, en lloc d’utilitzar el GUIDE (Graphical User Interface Development Enviroment) de MATLAB, per tal que sigui compatible entre les diferents versions d’aquest programa. En total hem fet 73 funcions en la interfície principal (d’aquestes, 10 pertanyen a la finestra d’importar i exportar) i 23 en la de l’Assistent. En aquest treball només explicarem 6 funcions i les 3 de creació d’aquestes interfícies per no fer-lo excessivament extens. Les funcions que explicarem són les més importants, ja sigui perquè s’utilitzen sovint, perquè, segons la complexitat McCabe, són les més complicades o perquè són necessàries pel processament del senyal. Passem cada entrada de dades per part de l’usuari per funcions que ens detectaran errors en aquesta entrada, com eliminació de zeros o de caràcters que no siguin números, com comprovar que són enters o que estan dins dels límits màxims i mínims que li pertoquen.

Does wheat genetically modified for disease resistance affect root-colonizing pseudomonads and arbuscular mycorrhizal fungi?

This study aimed to evaluate the impact of genetically modified (GM) wheat with introduced pm3b mildew resistance transgene, on two types of root-colonizing microorganisms, namely pseudomonads and arbuscular mycorrhizal fungi (AMF). Our investigations were carried out in field trials over three field seasons and at two locations. Serial dilution in selective King's B medium and microscopy were used to assess the abundance of cultivable pseudomonads and AMF, respectively. We developed a denaturing gradient gel electrophoresis (DGGE) method to characterize the diversity of the pqqC gene, which is involved in Pseudomonas phosphate solubilization. A major result was that in the first field season Pseudomonas abundances and diversity on roots of GM pm3b lines, but also on non-GM sister lines were different from those of the parental lines and conventional wheat cultivars. This indicates a strong effect of the procedures by which these plants were created, as GM and sister lines were generated via tissue cultures and propagated in the greenhouse. Moreover, Pseudomonas population sizes and DGGE profiles varied considerably between individual GM lines with different genomic locations of the pm3b transgene. At individual time points, differences in Pseudomonas and AMF accumulation between GM and control lines were detected, but they were not consistent and much less pronounced than differences detected between young and old plants, different conventional wheat cultivars or at different locations and field seasons. Thus, we conclude that impacts of GM wheat on plant-beneficial root-colonizing microorganisms are minor and not of ecological importance. The cultivation-independent pqqC-DGGE approach proved to be a useful tool for monitoring the dynamics of Pseudomonas populations in a wheat field and even sensitive enough for detecting population responses to altered plant physiology.

Gas sensing properties of catalytically modified WO3 with copper and vanadium for NH3 detection

Ammonia gas detection by pure and catalytically modified WO3 based gas sensor was analysed. The sensor response of pure WO3 to NH3 was not only rather low but also presented an abnormal behaviour, probably due to the unselective oxidation of ammonia to NOx. Copper and vanadium were introduced in different concentrations and the resulting material was annealed at different temperatures in order to improve the sensing properties for NH3 detection. The introduction of copper and vanadium as catalytic additives improved the response to NH3 and also eliminated the abnormal behaviour. Possible mechanisms of NH3 reaction over these materials are discussed. Sensor responses to other gases like NO2 or CO and the interference of humidity on ammonia detection were also analysed so as to choose the best sensing element.

Consequences of modified lipid and glucose metabolism on peripheral nervous system structure and function

284 million people worldwide suffered from type 2 diabetes mellitus (T2DM) in 2010, which will, in approximately half of them, lead to the development of diabetic peripheral neuropathy (DPN). Although DPN is the most common complication of diabetes mellitus and the leading cause of non-traumatic amputations its pathophysiology is still poorly understood. To get more insight into the molecular mechanism underlying DPN in T2DM, I used a rodent model of T2DM, the db/db mice.¦ln vivo electrophysiological recordings of diabetic animals indicated that in addition to reduced nerve conduction velocity db/db mice also present increased nerve excitability. Further ex vivo evaluation of the electrophysiological properties of db/db nerves clearly established a presence of the peripheral nerve hyperexcitability (PNH) phenotype in diabetic animals. Using pharmacological inhibitors we demonstrated that PNH is mostly mediated by the decreased activity of Kv1 channels. ln agreement with these data 1 observed that the diabetic condition led to a reduced presence of the Kv1.2 subunits in juxtaparanodal regions of db/db peripheral nerves whereas its mANA and protein expression levels were not affected. Lmportantly, I confirmed a loss of juxtaparanodal Kv1.2 subunits in nerve biopsies from type 2 diabetic patients. Together these observations indicate that the type 2 diabetic condition leads to potassium-channel mediated changes of nerve excitability thus identifying them as potential drug targets to treat sorne of the DPN related symptoms.¦Schwann cells ensheath and isolate peripheral axons by the production of myelin, which consists of lipids and proteins in a ratio of 2:1. Peripheral myelin protein 2 (= P2, Pmp2 or FABP8) was originally described as one of the most abundant myelin proteins in the peripheral nervous system. P2, which is a member of the fatty acid binding protein (FABP) family, is a 14.8 kDa cytosolic protein expressed on the cytoplasmic side of compact myelin membranes. As indicated by their name, the principal role of FABPs is thought to be the binding and transport of fatty acids.¦To study its role in myelinating glial cells I have recently generated a complete P2 knockout mouse model (P2-/-). I confirmed the loss of P2 in the sciatic nerve of P2-/- mice at the mRNA and protein level. Electrophysiological analysis of the adult (P56) mutant mice revealed a mild but significant reduction in the motor nerve conduction velocity. lnterestingly, this functional change was not accompanied by any detectable alterations in general myelin structure. However, I have observed significant alterations in the mRNA expression level of other FABPs, predominantly FABP9, in the PNS of P2-/- mice as compared to age-matched P2+/+ mice indicating a role of P2 in the glial myelin lipid metabolism.¦Le diabète de type 2 touche 284 million de personnes dans le monde en 2010 et son évolution conduit dans la moitié des cas à une neuropathie périphérique diabétique. Bien que la neuropathie périphérique soit la complication la plus courante du diabète pouvant conduire jusqu'à l'amputation, sa physiopathologie est aujourd'hui encore mal comprise. Dans le but d'améliorer les connaissances moléculaires expliquant les mécanismes de la neuropathie liée au diabète de type 2, j'ai utilisé un modèle murin du diabète de type 2, les souris db/db.¦ln vivo, les enregistrements éléctrophysiologiques des animaux diabétiques montrent qu'en plus d'une diminution de la vitesse de conduction nerveuse, les souris db/db présentent également une augmentation de l'excitabilité nerveuse. Des mesures menées Ex­ vivo ont montré l'existence d'un phénotype d'hyperexcitabilité sur les nerfs périphériques isolés d'animaux diabétiques. Grâce à l'utilisation d'inhibiteurs pharmacologiques, nous avons pu démontrer que l'hyperexcitabilité démontrée était due à une réduction d'activité des canaux Kv1. En accord avec ces données, j'ai observé qu'une situation de diabète conduisait à une diminution des canaux Kv1.2 aux régions juxta-paranodales des nerfs périphériques db/db, alors que l'expression du transcrit et de la protéine restait stable. J'ai également confirmé l'absence de canaux Kv1.2 aux juxta-paranoeuds de biopsies de nerfs de patients diabétiques. L'ensemble de ces observations montrent que les nerfs périphériques chez les patients atteints de diabète de type 2 est due à une diminution des canaux potassiques rapides juxtaparanodaux les identifiant ainsi comme des cibles thérapeutiques potentielles.¦Les cellules de Schwann enveloppent et isolent les axones périphériques d'une membrane spécialisée, la myéline, composée de deux fois plus de lipides que de protéines. La protéine P2 (Pmp2 "peripheral myelin protein 2" ou FABP8 "fatty acid binding protein") est l'une des protéines les plus abondantes au système nerveux périphérique. P2 appartient à la famille de protéines FABP liant et transportant les acides gras et est une protéine cytosolique de 14,8 kDa exprimée du côté cytoplasmique de la myéline compacte.¦Afin d'étudier le rôle de P2 dans les cellules de Schwann myélinisantes, j'ai généré une souris knockout (P2-/-). Après avoir validé l'absence de transcrit et de protéine P2 dans les nerfs sciatiques P2-/-, des mesures électrophysiologiques ont montré une réduction modérée mais significative de la vitesse de conduction du nerf moteur périphérique. Il est important de noter que ces changements fonctionnels n'ont pas pu être associés à quelconque changement dans la structure de la myéline. Cependant, j'ai observé dans les nerfs périphériques P2-/-, une altération significative du niveau d'expression d'ARNm d'autres FABPs et en particulier FABP9. Ce dernier résultat démontre l'importance du rôle de la protéine P2 dans le métabolisme lipidique de la myéline.

Intranasal administration of the synthetic polypeptide from the C-terminus of the circumsporozoite protein of Plasmodium berghei with the modified heat-labile toxin of Escherichia coli (LTK63) induces a complete protection against malaria challenge.

Needle-free procedures are very attractive ways to deliver vaccines because they diminish the risk of contamination and may reduce local reactions, pain or pain fear especially in young children with a consequence of increasing the vaccination coverage for the whole population. For this purpose, the possible development of a mucosal malaria vaccine was investigated. Intranasal immunization was performed in BALB/c mice using a well-studied Plasmodium berghei model antigen derived from the circumsporozoite protein with the modified heat-labile toxin of Escherichia coli (LTK63), which is devoid of any enzymatic activity compared to the wild type form. Here, we show that intranasal administration of the two compounds activates the T and B cell immune response locally and systemically. In addition, a total protection of mice is obtained upon a challenge with live sporozoites.

Evidence of chemical reactions in the hydroxyapatite laser ablation plume with a water atmosphere

The expansion dynamics of the ablation plume generated by KrF laser irradiation of hydroxyapatite targets in a 0.1 mbar water atmosphere has been studied by fast intensified charge coupled device imaging with the aid of optical bandpass filters. The aim of the filters is to isolate the emission of a single species, which allows separate analysis of its expansion. Images obtained without a filter revealed two emissive components in the plume, which expand at different velocities for delay times of up to 1.1 ¿s. The dynamics of the first component is similar to that of a spherical shock wave, whereas the second component, smaller than the first, expands at constant velocity. Images obtained through a 520 nm filter show that the luminous intensity distribution and evolution of emissive atomic calcium is almost identical to those of the first component of the total emission and that there is no contribution from this species to the emission from the second component of the plume. The analysis through a 780 nm filter reveals that atomic oxygen partially diffuses into the water atmosphere and that there is a contribution from this species to the emission from the second component. The last species studied here, calcium oxide, was analyzed by means of a 600 nm filter. The images revealed an intensity pattern more complex than those from the atomic species. Calcium oxide also contributes to the emission from the second component. Finally, all the experiments were repeated in a Ne atmosphere. Comparison of the images revealed chemical reactions between the first component of the plume and the water atmosphere.