Microstructure of the superior longitudinal fasciculus predicts stimulation-induced interference with on-line motor control.

A cortical visuomotor network, comprising the medial intraparietal sulcus (mIPS) and the dorsal premotor area (PMd), encodes the sensorimotor transformations required for the on-line control of reaching movements. How information is transmitted between these two regions and which pathways are involved, are less clear. Here, we use a multimodal approach combining repetitive transcranial magnetic stimulation (rTMS) and diffusion tensor imaging (DTI) to investigate whether structural connectivity in the 'reaching' circuit is associated to variations in the ability to control and update a movement. We induced a transient disruption of the neural processes underlying on-line motor adjustments by applying 1Hz rTMS over the mIPS. After the stimulation protocol, participants globally showed a reduction of the number of corrective trajectories during a reaching task that included unexpected visual perturbations. A voxel-based analysis revealed that participants exhibiting higher fractional anisotropy (FA) in the second branch of the superior longitudinal fasciculus (SLF II) suffered less rTMS-induced behavioral impact. These results indicate that the microstructural features of the white matter bundles within the parieto-frontal 'reaching' circuit play a prominent role when action reprogramming is interfered. Moreover, our study suggests that the structural alignment and cohesion of the white matter tracts might be used as a predictor to characterize the extent of motor impairments.

Decreasing educational differences in mortality over 40 years: evidence from the Turin Longitudinal Study (Italy)

BACKGROUND: Recent studies suggest that inequalities in premature mortality have continued to rise over the last decade in most European countries, but not in southern European countries. METHODS: In this study, we assess long-term trends (1971-2011) in absolute and relative educational inequalities in all-cause and cause-specific mortality in the Turin Longitudinal Study (Turin, Italy), a record-linkage study including all individuals resident in Turin in the 1971, 1981, 1991 and 2001 censuses, and aged 30-99 years (more than 2 million people). We examined mortality for all causes, cardiovascular disease (CVD), all cancers and specific cancers (lung, breast), as well as smoking and alcohol-related mortality. RESULTS: Overall mortality substantially decreased in all educational groups over the study period, although cancer rates only slightly declined. Absolute inequalities decreased for both genders (SII=962/694 in men/women in 1972-1976 and SII=531/259 in 2007-2011, p<0.01). Among men, absolute inequalities for CVD and alcohol-related causes declined (p<0.05), while remaining stable for other causes of death. Among women, declines in absolute inequalities were observed for CVD, smoking and alcohol-related causes and lung cancer (p<0.05). Relative inequalities in all-cause mortality remained stable for men and decreased for women (RII=1.92/2.03 in men/women in 1972-1976 and RII=2.15/1.32 in 2007-2011). Among men, relative inequalities increased for smoking-related causes, while among women they decreased for all cancers, CVD, smoking-related causes and lung cancer (p<0.05). CONCLUSIONS: Absolute inequalities in mortality strongly declined over the study period in both genders. Relative educational inequalities in mortality were generally stable among men; while they tended to narrow among women. In general, this study supports the hypothesis that educational inequalities in mortality have decreased in southern European countries.

Catalogue-tarif à prix forts et nets des journaux, revues et publications périodiques parus à Paris ... : contenant les titres complets par ordre alphabétique, les noms des rédacteurs, le format, la tomaison, la date d'origine, le mode de publication... : suivi d'une table systématique et du tarif postal pour la France et l'étranger / publié par Henri Le Soudier

1897 (A18).

Catalogue-tarif à prix forts et nets des journaux, revues et publications périodiques parus à Paris ... : contenant les titres complets par ordre alphabétique, les noms des rédacteurs, le format, la tomaison, la date d'origine, le mode de publication... : suivi d'une table systématique et du tarif postal pour la France et l'étranger / publié par Henri Le Soudier

Variante(s) de titre : Annuaire-tarif des journaux, revues et publications périodiques parus à Paris

Entry Mode Choice in a Hard Service Company

Pro gradun tavoitteena oli löytää tärkeimmät seikat, jotka vaikuttavat kansainvälisen operaatiomuodon valintaan. Tutkimuskohteena olivat suomalaiset pienet tai keskisuuret tuotteistetut ohjelmistopalveluyritykset. Tutkimusmenetelmänä käytettiin kvalitatiivista tutkimusta sekä case-tutkimusta. Tutkimus koostui kahdesta osasta: teoreettinen osa sekä empiirinen kahden case yrityksen analyysi. Operaatiomuodon valintaan vaikuttavat tekijät jaettiin sisäisiin (yritys, tuote ja päätöksentekijä), ulkoisiin (ala ja maa) ja operaatiomuodon (kontrolli, riski, resurssit, joustavuus, tuotot ja kulut) tekijöihin. Teoreettisesti operaatiomuodon valinta on erittäin monimutkainen päätös ja sitä on tutkittu monelta kannalta. Tämä empiirinen tutkimus osoittaa, että yrityksen resurssit olivat tärkein vaikuttava tekijä molemmissa yrityksissä.

On the longitudinal component of paraxial fields

The analysis of paraxial Gaussian beams features in most undergraduate courses in laser physics, advanced optics and photonics. These beams provide a simple model of the field generated in the resonant cavities of lasers, thus constituting a basic element for understanding laser theory. Usually, uniformly polarized beams are considered in the analytical calculations, with the electric field vibrating at normal planes to the propagation direction. However, such paraxial fields do not verify the Maxwell equations. In this paper we discuss how to overcome this apparent contradiction and evaluate the longitudinal component that any paraxial Gaussian beam should exhibit. Despite the fact that the assumption of a purely transverse paraxial field is useful and accurate, the inclusion of the above issue in the program helps students to clarify the importance of the electromagnetic nature of light, thus providing a more complete understanding of the paraxial approach.

Transverse and longitudinal components of the propagating and evanescent waves associated to radially-polarized nonparaxial fields

A comparison is established between the contributions of transverse and longitudinal components of both the propagating and the evanescent waves associated to freely propagating radially polarized nonparaxial beams. Attention is focused on those fields that remain radially polarized upon propagation. In terms of the plane-wave angular spectrum of these fields, analytical expressions are given for determining both the spatial shape of the above components and their relative weight integrated over the whole transverse plane. The results are applied to two kinds of doughnut-like beams with radial polarization, and we compare the behavior of such fields at two transverse planes.

Longitudinal monitoring of endogenous steroids in human serum by UHPLC-MS/MS as a tool to detect testosterone abuse in sports.

The detection of testosterone abuse in sports is routinely achieved through the 'steroidal module' of the Athlete Biological Passport by GC-MS(/MS) quantification of selected endogenous anabolic androgenic steroids (EAAS) from athletes' urines. To overcome some limitations of the "urinary steroid profile" such as the presence of confounding factors (ethnicity, enzyme polymorphism, bacterial contamination, and ethanol), ultrahigh performance liquid chromatography (UHPLC) measurements of blood concentrations of testosterone, its major metabolites, and precursors could represent an interesting and complementary strategy. In this work, two UHPLC-MS/MS methods were developed for the quantification of testosterone and related compounds in human serum, including major progestogens, corticoids, and estrogens. The validated methods were then used for the analyses of serum samples collected from 19 healthy male volunteers after oral and transdermal testosterone administration. Results from unsupervised multiway analysis allowed variations of target analytes to be assessed simultaneously over a 96-h time period. Except for alteration of concentration values due to the circadian rhythm, which concerns mainly corticosteroids, DHEA, and progesterone, significant variations linked to the oral and transdermal testosterone administration were observed for testosterone, DHT, and androstenedione. As a second step of analysis, the longitudinal monitoring of these biomarkers using intra-individual thresholds showed, in comparison to urine, significant improvements in the detection of testosterone administration, especially for volunteers with del/del genotype for phase II UGT2B17 enzyme, not sensitive to the main urinary marker, T/E ratio. A substantial extension of the detection window after transdermal testosterone administration was also observed in serum matrix. The longitudinal follow-up proposed in this study represents a first example of 'blood steroid profile' in doping control analysis, which can be proposed in the future as a complement to the 'urinary module' for improving steroid abuse detection capabilities.

Epigenetic regulatory elements: Recent advances in understanding their mode of action and use for recombinant protein production in mammalian cells.

Successful generation of high producing cell lines requires the generation of cell clones expressing the recombinant protein at high levels and the characterization of the clones' ability to maintain stable expression levels. The use of cis-acting epigenetic regulatory elements that improve this otherwise long and uncertain process has revolutionized recombinant protein production. Here we review and discuss new insights into the molecular mode of action of the matrix attachment regions (MARs) and ubiquitously-acting chromatin opening elements (UCOEs), i.e. cis-acting elements, and how these elements are being used to improve recombinant protein production. These elements can help maintain the chromatin environment of the transgene genomic integration locus in a transcriptionally favorable state, which increases the numbers of positive clones and the transgene expression levels. Moreover, the high producing clones tend to be more stable in long-term cultures even in the absence of selection pressure. Therefore, by increasing the probability of isolating a high producing clone, as well as by increasing transcription efficiency and stability, these elements can significantly reduce the time and cost required for producing large quantities of recombinant proteins.

Persistent spatial clusters of high body mass index in a Swiss urban population as revealed by the 5-year GeoCoLaus longitudinal study.

OBJECTIVE: Body mass index (BMI) may cluster in space among adults and be spatially dependent. Whether and how BMI clusters evolve over time in a population is currently unknown. We aimed to determine the spatial dependence of BMI and its 5-year evolution in a Swiss general adult urban population, taking into account the neighbourhood-level and individual-level characteristics. DESIGN: Cohort study. SETTING: Swiss general urban population. PARTICIPANTS: 6481 georeferenced individuals from the CoLaus cohort at baseline (age range 35-74 years, period=2003-2006) and 4460 at follow-up (period=2009-2012). OUTCOME MEASURES: Body weight and height were measured by trained healthcare professionals with participants standing without shoes in light indoor clothing. BMI was calculated as weight (kg) divided by height squared (m(2)). Participants were geocoded using their postal address (geographic coordinates of the place of residence). Getis-Ord Gi statistic was used to measure the spatial dependence of BMI values at baseline and its evolution at follow-up. RESULTS: BMI was not randomly distributed across the city. At baseline and at follow-up, significant clusters of high versus low BMIs were identified and remained stable during the two periods. These clusters were meaningfully attenuated after adjustment for neighbourhood-level income but not individual-level characteristics. Similar results were observed among participants who showed a significant weight gain. CONCLUSIONS: To the best of our knowledge, this is the first study to report longitudinal changes in BMI clusters in adults from a general population. Spatial clusters of high BMI persisted over a 5-year period and were mainly influenced by neighbourhood-level income.

The relation between internet use and overweight among adolescents: a longitudinal study in Switzerland.

OBJECTIVE: This longitudinal study aimed to investigate the characteristics and predictive risk factors of overweight among adolescents. The hypothesis was that baseline overweight predicted most overweight over time compared to other factors, especially excessive internet use. SUBJECTS: A sample of 621 youths were followed from age 14 (T0 Spring 2012) to age 16 (T1 Spring 2014) in Switzerland. Participants were divided into two groups according to their weight at the final assessment: overweight and non-overweight. At T0, participants reported demographic, health, substance use and internet use data. A logistic regression was performed to assess the explanatory variables of overweight at T1. Data are presented as adjusted odds ratios (aORs) with 95% confidence interval. RESULTS: The 2-year evolution showed a net BMI increase of 4.8%. Overweight adolescents were significantly more likely to be male, to live in an urban area, to be on a diet and to report using the internet more than 2 h per day on weekends at T0. However, with the addition of baseline overweight, only the excessive use of internet on weekends remained as an explanatory variable. An adolescent who was already overweight at T0 had a more than 20-fold risk (aOR 21.04) of being overweight 2 years later. Moreover, among adolescents becoming overweight between T0 and T1, internet use did not show any significant effect. CONCLUSION: The risk of being overweight is mostly influenced by weight status at baseline compared to excessive internet use. Thus, our results do not confirm the negative effect of internet on healthier activities. Internet use could at most reinforce an already existing risk of being overweight.

In Vivo Longitudinal (1)H MRS Study of Transgenic Mouse Models of Prion Disease in the Hippocampus and Cerebellum at 14.1 T.

In vivo (1)H MR spectroscopy allows the non invasive characterization of brain metabolites and it has been used for studying brain metabolic changes in a wide range of neurodegenerative diseases. The prion diseases form a group of fatal neurodegenerative diseases, also described as transmissible spongiform encephalopathies. The mechanism by which prions elicit brain damage remains unclear and therefore different transgenic mouse models of prion disease were created. We performed an in vivo longitudinal (1)H MR spectroscopy study at 14.1 T with the aim to measure the neurochemical profile of Prnp -/- and PrPΔ32-121 mice in the hippocampus and cerebellum. Using high-field MR spectroscopy we were able to analyze in details the in vivo brain metabolites in Prnp -/- and PrPΔ32-121 mice. An increase of myo-inositol, glutamate and lactate concentrations with a decrease of N-acetylaspartate concentrations were observed providing additional information to the previous measurements.

A probable dual mode of action for both L- and D-lactate neuroprotection in cerebral ischemia.

Lactate has been shown to offer neuroprotection in several pathologic conditions. This beneficial effect has been attributed to its use as an alternative energy substrate. However, recent description of the expression of the HCA1 receptor for lactate in the central nervous system calls for reassessment of the mechanism by which lactate exerts its neuroprotective effects. Here, we show that HCA1 receptor expression is enhanced 24 hours after reperfusion in an middle cerebral artery occlusion stroke model, in the ischemic cortex. Interestingly, intravenous injection of L-lactate at reperfusion led to further enhancement of HCA1 receptor expression in the cortex and striatum. Using an in vitro oxygen-glucose deprivation model, we show that the HCA1 receptor agonist 3,5-dihydroxybenzoic acid reduces cell death. We also observed that D-lactate, a reputedly non-metabolizable substrate but partial HCA1 receptor agonist, also provided neuroprotection in both in vitro and in vivo ischemia models. Quite unexpectedly, we show D-lactate to be partly extracted and oxidized by the rodent brain. Finally, pyruvate offered neuroprotection in vitro whereas acetate was ineffective. Our data suggest that L- and D-lactate offer neuroprotection in ischemia most likely by acting as both an HCA1 receptor agonist for non-astrocytic (most likely neuronal) cells as well as an energy substrate.