The Magnetic Acoustic Change Complex and Mismatch Field:A Comparison of Neurophysiological Measures of Auditory Discrimination

The Acoustic Change Complex (ACC), a P1-N1-P2-like event-related response to changes in a continuous sound, has been suggested as a reliable, objective, and efficient test of auditory discrimination. We used magnetoencephalography to compare the magnetic ACC (mACC) to the more widely used mismatch field (MMF). Brain responses of 14 adults were recorded during mACC and MMF paradigms involving the same pitch and vowel changes in a synthetic vowel sound. Analyses of peak amplitudes revealed a significant interaction between stimulus and paradigm: for the MMF, the response was greater for vowel changes than for pitch changes, whereas, for the mACC, the pattern was reversed. A similar interaction was observed for the signal to noise ratio and single-trial analysis of individual participants’ responses showed that the MMF to Pitch changes was elicited less consistently than the other three responses. Results support the view that the ACC/mACC is a robust and efficient measure of simple auditory discrimination, particularly when researchers or clinicians are interested in the responses of individual listeners. However, the differential sensitivity of the two paradigms to the same acoustic changes indicates that the mACC and MMF are indices of different aspects of auditory processing and should, therefore, be seen as complementary rather than competing neurophysiological measures

Epistasis between the MHC and the RCAα block in primary Sjögren syndrome

ObjectiveThe RCA alpha block (Regulators of Complement Activation, 1q32) contains critical complement regulatory genes such as CR1 and MCP. This study examined RCA alpha block haplotype associations with both disease susceptibility and diversification of the anti-Ro/La autoantibody response in primary Sjögren syndrome (pSS).Methods115 patients with pSS and 98 controls were included in the study. 93 of 109 (85%) of the patients with pSS were seropositive for Ro/La autoantibodies. The Genomic Matching Technique (GMT) was used to define RCA alpha block ancestral haplotypes (AH).ResultsRCA alpha block haplotypes, AH1 and AH3, were both associated with autoantibody-positive pSS (p = 0.0003). Autoantibody associations with both HLA DR3 and DR15 have been previously defined. There was an epistatic interaction (p = 0.023) between RCA alpha AH1 and HLA DR3, and this genotypic combination was present in 48% of autoantibody-positive patients with pSS compared with 8% of controls. This epistasis is most simply attributable to an interaction between C4 and its receptor, CR1, encoded within the RCA alpha block. Both DR3 and a relative C4 deficiency are carried on the major histocompatibility complex 8.1 ancestral haplotype. Only four of 92 (4%) autoantibody-positive patients with pSS did not carry any risk RCA alpha or HLA haplotype, compared with 36 of 96 (38%) controls, and there were differences in haplotype frequencies within autoantibody subsets of pSS.ConclusionsNormal population variation in the RCA alpha block, in addition to the major histocompatibility complex, contributes genetic susceptibility to systemic autoimmune disease and the autoantibody response. This finding provides evidence for the role of regulation of complement activation in disease pathogenesis.S. Lester, C. McLure, J. Williamson, P. Bardy, M. Rischmueller, R. L. Dawkin

Soft Skills and Job Opportunities of Migrants: Systemic Relationships in the Labor Market

The skills of migrants, the skills of existing workers, and the characteristics of the host economy are critical factors that impact the labor market in any country. Studying these effects is a critical area of research with much of the research being specific to time and place. There are studies on the UK which look into the wage effects of immigration and the impact on unemployment A study on Denmark found that an increase in the supply of refugee-country immigrants pushed less educated native workers (especially the young and low-tenured ones) to pursue less manual-intensive occupations. So, immigration had positive effects on unskilled wages, employment and occupational mobility. This has led to critical assessments of the skills brought in by migrants who have a higher level of education. This is occurring to quite an extent in present-day immigration to Europe. This paper draws on a study performed by the authors on African nationals with an academic background and who study, live and work in Germany. They were asked to complete an online questionnaire on management soft skills. The results revealed that the African migrants appear to be quite aware of the specific soft skills they owe to their cultural background, which ultimately might make them well equipped for better job opportunities when they actively apply them in their work environment. In continuance, this paper contrasts those findings with the results of a large European survey of migrants’ soft skills conducted with companies’ heads, personnel managers and business associations. Mirroring the results of both studies provides an insight into the extent in which the opinions on migrants’ soft skills align and where they differ. This leads to infer that while migrants’ skills enhance their ability to enter into the labor market, the skills also shape the market by creating niches for employment and this in turn changes how migrants deploy their skills. There are various conclusions to be drawn: One is that integrating migrants into the labor market requires creative leadership and ethically founded decision-making: Both employers and employer associations must seek to fully utilize all the skills provided by the new entrants to the labor market. From a theoretical perspective, the two sets (of data but of interviewees as well) represent two distinct agglomerations of elements that are interrelated within each set, and they are also relating the sets to each other. This embeds a variety of systems-thinking constructs. Co-creation is one, and it regards to building a new set of information from not only the observations on skills offered and required but also from the developments that are triggered when offer and demand meet. One other is coalescing of equi-finality and multi-finality to arrive at a balance between needs of job-seekers and the job offers that can be satisfied short-term or for which long-term solutions are required. A third one is conjoining self-organization and relationality where skills development and labor market conditions enter into a systemic relation. For applying this concept, a parallel can be drawn to the innovation deployment projects that are run within the European Commission’s Framework Programs (Kapsali, 2011). With regard to generating new opportunities in the job market, a systems-thinking interpretation would be that of an auto-poietic system (the development of skills) that interacts with the environment (the job market) and processes self-reference and other-reference. The paper evaluates the applicability of these concepts to the phenomenon of migrants in the labor market

Moving in unison after perceptual interruption

Humans interact in groups through various perception and action channels. The continuity of interaction despite a transient loss of perceptual contact often exists and contributes to goal achievement. Here, we study the dynamics of this continuity, in two experiments involving groups of participants (N= 7) synchronizing their movements in space and in time. We show that behavioural unison can be maintained after perceptual contact has been lost, for about 7s. Agent similarity and spatial configuration in the group modulated synchronization performance, differently so when perceptual interaction was present or when it was memorized. Modelling these data through a network of oscillators enabled us to clarify the double origin of this memory effect, of individual and social nature. These results shed new light into why humans continue to move in unison after perceptual interruption, and are consequential for a wide variety of applications at work, in art and in sport

Record RF performance of standard 90 nm CMOS technology

We have optimized 3 key RF devices realized in standard logic 90 nm CMOS technology and report a record performance in terms of n-MOS maximum oscillation frequency f/sub max/ (280 GHz), varactor tuning range and varactor and inductor quality factor

Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells.

Our understanding of Alzheimer's disease pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic form of the disease. It may be possible to overcome these challenges by reprogramming primary cells from patients into induced pluripotent stem cells (iPSCs). Here we reprogrammed primary fibroblasts from two patients with familial Alzheimer's disease, both caused by a duplication of the amyloid-β precursor protein gene (APP; termed APP(Dp)), two with sporadic Alzheimer's disease (termed sAD1, sAD2) and two non-demented control individuals into iPSC lines. Neurons from differentiated cultures were purified with fluorescence-activated cell sorting and characterized. Purified cultures contained more than 90% neurons, clustered with fetal brain messenger RNA samples by microarray criteria, and could form functional synaptic contacts. Virtually all cells exhibited normal electrophysiological activity. Relative to controls, iPSC-derived, purified neurons from the two APP(Dp) patients and patient sAD2 exhibited significantly higher levels of the pathological markers amyloid-β(1-40), phospho-tau(Thr 231) and active glycogen synthase kinase-3β (aGSK-3β). Neurons from APP(Dp) and sAD2 patients also accumulated large RAB5-positive early endosomes compared to controls. Treatment of purified neurons with β-secretase inhibitors, but not γ-secretase inhibitors, caused significant reductions in phospho-Tau(Thr 231) and aGSK-3β levels. These results suggest a direct relationship between APP proteolytic processing, but not amyloid-β, in GSK-3β activation and tau phosphorylation in human neurons. Additionally, we observed that neurons with the genome of one sAD patient exhibited the phenotypes seen in familial Alzheimer's disease samples. More generally, we demonstrate that iPSC technology can be used to observe phenotypes relevant to Alzheimer's disease, even though it can take decades for overt disease to manifest in patients

Fertilité des sols: conclusions du rapport sur l'état des sols de France

Les sols constituent une ressource naturelle non renouvelable. Leurs usages et leur devenir représentent un enjeu collectif majeur, tant pour les activités agricoles ou sylvicoles que pour la préservation de la qualité de notre environnement. Après dix ans de travaux, le Groupement d’Intérêt Scientifique sur les sols, le Gis Sol, a dressé le premier bilan scientifiquement quantifié de l’état des sols de France métropolitaine et d’Outre-mer dans un rapport sur l’état des sols de France publié en 2011. Ce rapport relève des points positifs mais également un certain nombre de préoccupations du point de vue de la fertilité. Les sols agricoles ne présentent pas d’évolution mesurable de leur acidité, ce quiindique une bonne gestion du pH à l’échelle nationale. Le rapport fait en revanche état de teneurs en phosphore relativement faibles pour de nombreux sols, et à l’inverse de situations d’excédents très préoccupantes en raison de son impact sur la qualité des eaux et l’eutrophisation des milieux. Il pose ainsi la question de la durabilité à long terme du système agricole actuel et celle d’une meilleure valorisation des effluents d’élevage. D’assez nombreuses situations pourraient également être susceptibles de provoquer des carences en oligo-éléments pour des cultures exigeantes. Enfin, une inquiétude majeure concerne la progression de l’artificialisation des sols, qui s’est accélérée durant la dernière décennie et occasionne des pertes importantes de sols agricoles.Soils are a non-renewable, natural resource. Their uses and their future represent, therefore, a collective issue for agricultural and forestry production, as well as for the preservation of our environment. After ten years of work, the “Groupement d’intérêt scientifique sur les sols”, the Gis Sol (Soils Scientific Interest Group) has presented the first appraisal of soil quality in mainland France and its overseas territories in a report on the state of the soils in France published in 2011. This appraisal shows evidence for positive points but also highlights some concerns regarding soil fertility. Agricultural soils do not show a measurable change in their acidity, thus indicating an efficient management of pH at a national level. On the other hand, the report shows relatively low phosphorus levels for numerous soils, and inversely situations of structural excess which remain very worrying due to its impact on water quality and on the eutrophication of the environments. It also raises the questionsof the long-term sustainability of current cultivation systems and of a better treatment of effluents from livestock farming. Numerous situations also seem to be incompatible, for certain oligo-elements, with demanding cultures. At last, a major concern is the development of soil sealing, which has accelerated over the last decade and is responsible for the loss of large areas of agricultural soils

Prospective assessment of integrating the existing emergency medical system with automated external defibrillators fully operated by volunteers and laypersons for out-of-hospital cardiac arrest: the Brescia Early Defibrillation Study (BEDS)

AIMS: There are few data on the outcomes of cardiac arrest (CA) victims when the defibrillation capability of broad rural and urban territories is fully operated by volunteers and laypersons. METHODS AND RESULTS: In this study, we investigated whether a programme based on diffuse deployment of automated external defibrillators (AEDs) operated by 2186 trained volunteers and laypersons across the County of Brescia, Italy (area: 4826 km(2); population: 1 112 628), would safely and effectively impact the current survival among victims of out-of-hospital CA. Forty-nine AEDs were added to the former emergency medical system that uses manual EDs in the emergency department of 10 county hospitals and in five medically equipped ambulances. The primary endpoint was survival free of neurological impairment at 1-year follow-up. Data were analysed in 692 victims before and in 702 victims after the deployment of the AEDs. Survival increased from 0.9% (95% CI 0.4-1.8%) in the historical cohort to 3.0% (95% CI 1.7-4.3%) (P=0.0015), despite similar intervals from dispatch to arrival at the site of collapse [median (quartile range): 7 (4) min vs. 6 (6) min]. Increase of survival was noted both in the urban [from 1.4% (95% CI 0.4-3.4 %) to 4.0% (95% CI 2.0-6.9 %), P=0.024] and in the rural territory [from 0.5% (95% CI 0.1-1.6%) to 2.5% (95% CI 1.3-4.2%), P=0.013]. The additional costs per quality-adjusted life year saved amounted to euro39 388 (95% CI euro16 731-49 329) during the start-up phase of the study and to euro23 661 (95% CI euro10 327-35 528) at steady state. CONCLUSION: Diffuse implementation of AEDs fully operated by trained volunteers and laypersons within a broad and unselected environment proved safe and was associated with a significantly higher long-term survival of CA victims

Universal Role for HLA-C and KIR2Dl Ligand Mismatch in Severe Acute Graft-Versus-Host Disease After Unrelated Donor Hematopoietic Stem Cell Transplantation (U-HSCT) in Japanese and Caucasian Transplant Recipients: An Analysis on Behalf of International Histocompatibility Working Group in Hematopoietic Cell Transplantation

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Assessment of adult formulas for glomerular filtration rate estimation in children.

BACKGROUND: Estimated glomerular filtration rate (eGFR) is an important diagnostic instrument in clinical practice. The National Kidney Foundation-Kidney Disease Quality Initiative (NKF-KDOQI) guidelines do not recommend using formulas developed for adults to estimate GFR in children; however, studies confirming these recommendations are scarce. The aim of our study was to evaluate the accuracy of the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, the Modification of Diet in Renal Disease (MDRD) formula, and the Cockcroft-Gault formula in children with various stages of chronic kidney disease (CKD). METHODS: A total of 550 inulin clearance (iGFR) measurements for 391 children were analyzed. The cohort was divided into three groups: group 1, with iGFR >90 ml/min/1.73 m(2); group 2, with iGFR between 60 and 90 ml/min/1.73 m(2); group 3, with iGFR of <60 ml/min/1.73 m(2). RESULTS: All formulas overestimate iGFR with a significant bias (p < 0.001), present poor accuracies, and have poor Spearman correlations. For an accuracy of 10 %, only 11, 6, and 27 % of the eGFRs are accurate when using the MDRD, CKD-EPI, and Cockcroft-Gault formulas, respectively. For an accuracy of 30 %, these formulas do not reach the NKF-KDOQI guidelines for validation, with only 25, 20, and 70 % of the eGFRs, respectively, being accurate. CONCLUSIONS: Based on our results, the performances of all of these formulas are unreliable for eGFR in children across all CKD stages and cannot therefore be applied in the pediatric population group