Repeatability analysis of global and local metrics of brain structural networks

Computational network analysis provides new methods to analyze the human connectome. Brain structural networks can be characterized by global and local metrics that recently gave promising insights for diagnosis and further understanding of neurological, psychiatric and neurodegenerative disorders. In order to ensure the validity of results in clinical settings the precision and repeatability of the networks and the associated metrics must be evaluated. In the present study, nineteen healthy subjects underwent two consecutive measurements enabling us to test reproducibility of the brain network and its global and local metrics. As it is known that the network topology depends on the network density, the effects of setting a common density threshold for all networks were also assessed. Results showed good to excellent repeatability for global metrics, while for local metrics it was more variable and some metrics were found to have locally poor repeatability. Moreover, between subjects differences were slightly inflated when the density was not fixed. At the global level, these findings confirm previous results on the validity of global network metrics as clinical biomarkers. However, the new results in our work indicate that the remaining variability at the local level as well as the effect of methodological characteristics on the network topology should be considered in the analysis of brain structural networks and especially in networks comparisons.

The Swiss Schools have been Governed by Local Lay Authorities

After the introduction of the liberal-democratic constitutions in the Swiss cantons in the first half of the 1830ies the grid of existing schools has been systemized and broadly expanded. The school systems have ever since been characterized by one key element: a special local authority type called „Schulkommission“ or „Schulpflege“. They take the form of committees consisting of laymen that are appointed by democratic elections like all the other executive bodies on the different federal levels in Switzerland. When it comes to their obligations and activities these community level school committees conform very much to the school boards in the American and Canadian school systems. They are accountable for the selection and supervision of the teachers. They approve decisions about the school careers of pupils and about curricular matters like the choice of school books. Normally their members are elected by the local voters for four year terms of office (reelection remains possible) and with regard to pedagogics they normally are non-professionals. The board members are responsible for classes and teachers assigned to them and they have to go to see them periodically. These visitations and the board meetings each month together with the teachers enable the board members to attain a deep insight into what happens in their schools over the course of their term of office. But they are confronted as laymen with a professional teaching staff and with educational experts in the public administration. Nevertheless this form of executive power by non-professionals is constitutive for the state governance in the Swiss as well as in other national political environments. It corresponds to the principles of subsidiarity and militia and therefore allows for a strong accentuation of liberty and the right of self-determination, two axioms at the very base of democratic federalist ideology. This governance architecture with this strong accent on local anchorage features substantial advantages for the legitimacy and acceptability of political and administrative decisions. And this is relevant especially in the educational area because the rearing of the offspring is a project of hope and, besides, quite costly. In the public opinion such supervision bodies staffed by laymen seem to have certain credibility advances in comparison with the professional administration. They are given credit to be capable of impeding the waste of common financial resources and of warranting the protection and the fostering of the community’s children at once. Especially because of their non-professional character they are trusted to be reliably immune against organizational blindness and they seem to be able to defend the interests of the local community against the standardization and centralization aspirations originating from the administrational expertocracy. In the paper these common rationales will be underpinned by results of a comprehensive historical analysis of the Session protocols of three Bernese school commissions from 1835 to 2005.

Naive B-cell trafficking is shaped by local chemokine availability and LFA-1-independent stromal interactions.

It is not known how naive B cells compute divergent chemoattractant signals of the T-cell area and B-cell follicles during in vivo migration. Here, we used two-photon microscopy of peripheral lymph nodes (PLNs) to analyze the prototype G-protein-coupled receptors (GPCRs) CXCR4, CXCR5, and CCR7 during B-cell migration, as well as the integrin LFA-1 for stromal guidance. CXCR4 and CCR7 did not influence parenchymal B-cell motility and distribution, despite their role during B-cell arrest in venules. In contrast, CXCR5 played a nonredundant role in B-cell motility in follicles and in the T-cell area. B-cell migration in the T-cell area followed a random guided walk model, arguing against directed migration in vivo. LFA-1, but not α4 integrins, contributed to B-cell motility in PLNs. However, stromal network guidance was LFA-1 independent, uncoupling integrin-dependent migration from stromal attachment. Finally, we observed that despite a 20-fold reduction of chemokine expression in virus-challenged PLNs, CXCR5 remained essential for B-cell screening of antigen-presenting cells. Our data provide an overview of the contribution of prototype GPCRs and integrins during naive B-cell migration and shed light on the local chemokine availability that these cells compute.

The importance of biotic interactions and local adaptation for plant response to environmental changes: field evidence along an elevational gradient

Predicting the response of species to environmental changes is a great and on-going challenge for ecologists, and this requires a more in-depth understanding of the importance of biotic interactions and the population structuration in the landscape. Using a reciprocal transplantation experiment, we tested the response of five species to an elevational gradient. This was combined to a neighbour removal treatment to test the importance of local adaptation and biotic interactions. The trait studied was performance measured as survival and biomass. Species response varied along the elevational gradient, but with no consistent pattern. Performance of species was influenced by environmental conditions occurring locally at each site, as well as by positive or negative effects of the surrounding vegetation. Indeed, we observed a shift from competition for biomass to facilitation for survival as a response to the increase in environmental stress occurring in the different sites. Unlike previous studies pointing out an increase of stress along the elevation gradient, our results supported a stress gradient related to water availability, which was not strictly parallel to the elevational gradient. For three of our species, we observed a greater biomass production for the population coming from the site where the species was dominant (central population) compared to population sampled at the limit of the distribution (marginal population). Nevertheless, we did not observe any pattern of local adaptation that could indicate adaptation of populations to a particular habitat. Altogether, our results highlighted the great ability of plant species to cope with environmental changes, with no local adaptation and great variability in response to local conditions. Our study confirms the importance of taking into account biotic interactions and population structure occurring at local scale in the prediction of communities’ responses to global environmental changes.

Local Stereology of Tensors of Convex Bodies

In this paper, we present local stereological estimators of Minkowski tensors defined on convex bodies in ℝ d . Special cases cover a number of well-known local stereological estimators of volume and surface area in ℝ3, but the general set-up also provides new local stereological estimators of various types of centres of gravity and tensors of rank two. Rank two tensors can be represented as ellipsoids and contain information about shape and orientation. The performance of some of the estimators of centres of gravity and volume tensors of rank two is investigated by simulation.

Genetic diversity, phenotypic variation and local adaptation in the alpine landscape: case studies with alpine plant species

Plant survival in alpine landscapes is constantly challenged by the harsh and often unpredictable environmental conditions. Steep environmental gradients and patchy distribution of habitats lead to small size and spatial isolation of populations and restrict gene flow. Agricultural land use has further increased the diversity of habitats below and above the treeline. We studied the consequences of the highly structured alpine landscape for evolutionary processes in four study plants: Epilobium fleischeri, Geum reptans, Campanula thyrsoides and Poa alpina. The main questions were: (1) How is genetic diversity distributed within and among populations and is it affected by altitude, population size or land use? (2) Do reproductive traits such as allocation to sexual or vegetative reproduction vary with altitude or land use? Furthermore, we studied if seed weight increases with altitude. Within-population genetic diversity of the four species was high and mostly not related to altitude and population size. Nevertheless, genetic differentiation among populations was pronounced and strongly increasing with distance. In Poa alpina genetic diversity was affected by land use. Results suggest considerable genetic drift among populations of alpine plants. Reproductive allocation was affected by altitude and land use in Poa alpina and by succession in Geum reptans. Seed weight was usually higher in alpine species than in related lowland species. We conclude that the evolutionary potential to respond to global change is mostly intact in alpine plants, even at high altitude. Phenotypic variability is shaped by adaptive as well as by random evolutionary processes; moreover plastic responses to growth conditions seem to be crucial for survival of plants in the alpine landscape.

Local and general anaesthesia do not influence outcome of transfemoral aortic valve implantation.

BACKGROUND There is great variability for the type of anaesthesia used during TAVI, with no clear consensus coming from comparative studies or guidelines. We sought to detect regional differences in the anaesthetic management of patients undergoing transcatheter aortic valve implantation (TAVI) in Europe and to evaluate the relationship between type of anaesthesia and in-hospital and 1year outcome. METHODS Between January 2011 and May 2012 the Sentinel European TAVI Pilot Registry enrolled 2807 patients treated via a transfemoral approach using either local (LA-group, 1095 patients, 39%) or general anaesthesia (GA-group, 1712 patients, 61%). RESULTS A wide variation in LA use was evident amongst the 10 participating countries. The use of LA has increased over time (from a mean of 37.5% of procedures in the first year, to 57% in last 6months, p<0.01). MI, major stroke as well as in-hospital death rate (7.0% LA vs 5.3% GA, p=0.053) had a similar incidence between groups, confirmed in multivariate regression analysis after adjusting for confounders. Dividing our population in tertiles according to the Log-EuroSCORE we found similar mortality under LA, whilst mortality was higher in the highest risk tertile under GA. Survival at 1year, compared by Kaplan-Meier analysis, was similar between groups (log-rank: p=0.1505). CONCLUSIONS Selection of anaesthesia appears to be more influenced by national practice and operator preference than patient characteristics. In the absence of an observed difference in outcomes for either approach, there is no compelling argument to suggest that operators and centres should change their anaesthetic practice.

Fine-scale population structure analysis of seven local Swiss sheep breeds using genome-wide SNP data

As part of the global sheep Hapmap project, 24 individuals from each of seven indigenous Swiss sheep breeds (Bundner Oberländer sheep (BOS), Engadine Red sheep (ERS), Swiss Black-Brown Mountain sheep (SBS), Swiss Mirror sheep (SMS), Swiss White Alpine (SWA) sheep, Valais Blacknose sheep (VBS) and Valais Red sheep (VRS)), were genotyped using Illumina’s Ovine SNP50 BeadChip. In total, 167 animals were subjected to a detailed analysis for genetic diversity using 45 193 informative single nucleotide polymorphisms. The results of the phylogenetic analyses supported the known proximity between populations such as VBS and VRS or SMS and SWA. Average genomic relatedness within a breed was found to be 12 percent (BOS), 5 percent (ERS), 9 percent (SBS), 10 percent (SMS), 9 percent (SWA), 12 percent (VBS) and 20 percent (VRS). Furthermore, genomic relationships between breeds were found for single individuals from SWA and SMS, VRS and VBS as well as VRS and BOS. In addition, seven out of 40 indicated parent–offspring pairs could not be confirmed. These results were further supported by results from the genome-wide population cluster analysis. This study provides a better understanding of fine-scale population structures within and between Swiss sheep breeds. This relevant information will help to increase the conservation activities of the local Swiss sheep breeds.

Sources and contributions of wood smoke during winter in London: assessing local and regional influences

Determining the contribution of wood smoke to air pollution in large cities such as London is becoming increasingly important due to the changing nature of domestic heating in urban areas. During winter, biomass burning emissions have been identified as a major cause of exceedances of European air quality limits. The aim of this work was to quantify the contribution of biomass burning in London to concentrations of PM2:5 and determine whether local emissions or regional contributions were the main source of biomass smoke. To achieve this, a number of biomass burning chemical tracers were analysed at a site within central London and two sites in surrounding rural areas. Concentrations of levoglucosan, elemental carbon (EC), organic carbon (OC) and K+ were generally well correlated across the three sites. At all the sites, biomass burning was found to be a source of OC and EC, with the largest contribution of EC from traffic emissions, while for OC the dominant fraction included contributions from secondary organic aerosols, primary biogenic and cooking sources. Source apportionment of the EC and OC was found to give reasonable estimation of the total carbon from non-fossil and fossil fuel sources based upon comparison with estimates derived from 14C analysis. Aethalometer-derived black carbon data were also apportioned into the contributions frombiomass burning and traffic and showed trends similar to those observed for EC. Mean wood smoke mass at the sites was estimated to range from 0.78 to 1.0 μgm-3 during the campaign in January–February 2012. Measurements on a 160m tower in London suggested a similar ratio of brown to black carbon (reflecting wood burning and traffic respectively) in regional and London air. Peaks in the levoglucosan and K+ concentrations were observed to coincide with low ambient temperature, consistent with domestic heating as a major contributing local source in London. Overall, the source of biomass smoke in London was concluded to be a background regional source overlaid by contributions from local domestic burning emissions. This could have implications when considering future emission control strategies during winter and may be the focus of future work in order to better determine the contributing local sources.

Ophthalmic complications and local anesthesia. Pathophysiology and types of eye complications after intraoral dental anesthesia, and clinical recommendations

The present article reviews the different types of ophthalmologic complications following administration of intraoral local anesthesia. Since the first report by Brain in 1936, case reports about that topic have been published regularly in the literature. However, clinical studies evaluating the incidence of ophthalmologic complications after intraoral local anesthesia are rarely available. Previous data point to a frequency ranging from 0.03% to 0.13%. The most frequently described ophthalmologic complications include diplopia (double vision), ptosis (drooping of upper eyelid), and mydriasis (dilatation of pupil). Disorders that rather affect periorbital structures than the eye directly include facial paralysis and periorbital blanching (angiospasm). Diverse pathophysiologic mechanisms and causes have been reported in the literature, with the inadvertent intravascular administration of the local anesthetic considered the primary reason. The agent as well as the vasopressor is transported retrogradely via arteries or veins to the orbit or to periorbital structures (such as the cavernous sinus) with subsequent anesthesia of nerves and paralysis of muscles distant from the oral cavity. In general the ophthalmologic complications begin shortly after administration of the local anesthesia, and disappear once the local anesthesia has subsided.

Dynamics of Traditional Ecological Knowledge, Local Use and Conservation of Native Trees and Shrubs in the Bolivian Andes

Native trees and shrubs are essential components of rural landscapes in the semi-arid inner-Andean valleys of Bolivia. They can be found as hedges and bushes in various agroecosystems such as terrace walls, slopes, field boundaries and fallow land. Their distribution and floristic composition are the result of dynamic spatial and temporal interactions between local farmers and the environment. Local uses of natural resources and biodiversity reflect the constantly evolving Andean culture, which can be generally characterised as an intertwining of the human, natural, and spiritual worlds. The aim of the present ethnobotanical study was to analyse the dynamics of traditional ecological knowledge, to ascertain local farmers’ perceptions and uses of native woody species in Andean communities and to associate the results with local conservation activities for the trees and shrubs concerned. Our case study was carried out within two communities of the Tunari National Park (Dept. Cochabamba) in Bolivia. For data collection, research methods from social science (semi-structured interviews, participative observation, participatory mapping) as well as vegetation surveys were combined. Local actors included women and men of all ages as well as families from different social categories and altitudinal levels of permanent residence. Our study indicates that, due to a multitude of socio-economic pressures (e.g. migration of young people) as well as changes in use of biodiversity (e.g. replacement of native by exotic introduced species), the traditional ecological knowledge base of native trees and shrubs and their respective uses has become diminished over time. In many cases it has led to a decline in people’s awareness of native species and as a consequence their practical, emotional and spiritual relationships with them have been lost. However, results also show that applied traditional ecological knowledge has led to local conservation strategies, which have succeeded in protecting those tree and shrub species which are most widely regarded for their multifunctional, constant and exclusive uses (e.g. Schinus molle, Prosopis laevigata, Baccharis dracunculifolia). The presentation will discuss the question if and how applied traditional ecological knowledge positively contributes to local initiatives of sustainable use and conservation of biodiversity in rural areas.

From local perception to global perspective

Recent sociological studies show that over short time periods the large day-to-day, month-to-month or year-to-year variations in weather at a specific location can influence and potentially bias our perception of climate change, a more long-term and global phenomenon. By weighting local temperature anomalies with the number of people that experience them and considering longer time periods, we illustrate that the share of the world population exposed to warmer-than-normal temperatures has steadily increased during the past few decades. Therefore, warming is experienced by an increasing number of individuals, counter to what might be simply inferred from global mean temperature anomalies. This behaviour is well-captured by current climate models, offering an opportunity to increase confidence in future projections of climate change irrespective of the personal local perception of weather.

Interlaboratory variability of MIB1 staining in well-differentiated pancreatic neuroendocrine tumors

Neuroendocrine tumors (NET) are routinely graded and staged to judge prognosis. Proliferation index using MIB1 staining has been introduced to assess grading. There are vivid discussions on cutoff definitions, automated counting, and interobserver variability. However, no data exist regarding interlaboratory reproducibility for low proliferation indices which are of importance to discriminate between G1 and G2 NET. We performed MIB1 staining in three different university hospital-based pathology laboratories on a tissue micro array (TMA) of a well-characterized patient cohort, containing pancreatic NET of 61 patients. To calculate the proliferation index, number of positive tumor nuclei was divided by the total number of tumor nuclei. Labeling index was compared to mitotic counts in whole tissue sections and to clinical outcome. Linear regression analysis, intraclass comparison, and log-rank analysis were performed. Intraclass correlation showed moderate-to-fair agreement. Especially low proliferating tumors were affected by interlaboratory differences. Log-rank analysis was performed for each lab and resulted in three different cutoffs (5.0, 3.0, and 0.5 %). Every calculated cutoff stratified the patient cohort to a significant extent for the underlying stain (p < 0.001, <0.001, and <0.001) but showed no or lesser significance when applied to the other stains. Significant and relevant interlab differences for MIB1 exist. Since the MIB1 proliferation index influences grading, local cutoffs or external standardization should urgently be introduced to achieve reliability and reproducibility.

Local Heat Application for the Treatment of Buruli Ulcer: Results of a Phase II Open Label Single Center Non Comparative Clinical Trial.

BACKGROUND Buruli ulcer (BU) is a necrotizing skin disease most prevalent among West African children. The causative organism, Mycobacterium ulcerans, is sensitive to temperatures above 37°C. We investigated the safety and efficacy of a local heat application device based on phase change material. METHODS In a phase II open label single center noncomparative clinical trial (ISRCTN 72102977) under GCP standards in Cameroon, laboratory confirmed BU patients received up to 8 weeks of heat treatment. We assessed efficacy based on the endpoints 'absence of clinical BU specific features' or 'wound closure' within 6 months ("primary cure"), and 'absence of clinical recurrence within 24 month' ("definite cure"). RESULTS Of 53 patients 51 (96%) had ulcerative disease. 62% were classified as World Health Organization category II, 19% each as category I and III. The average lesion size was 45 cm(2). Within 6 months after completion of heat treatment 92.4% (49 of 53, 95% confidence interval [CI], 81.8% to 98.0%) achieved cure of their primary lesion. At 24 months follow-up 83.7% (41 of 49, 95% CI, 70.3% to 92.7%) of patients with primary cure remained free of recurrence. Heat treatment was well tolerated; adverse effects were occasional mild local skin reactions. CONCLUSIONS Local thermotherapy is a highly effective, simple, cheap and safe treatment for M. ulcerans disease. It has in particular potential as home-based remedy for BU suspicious lesions at community level where laboratory confirmation is not available. CLINICAL TRIALS REGISTRATION ISRCT 72102977.

A first chironomid-based summer temperature reconstruction (13–5 ka BP) around 49°N in inland Europe compared with local lake development

Temperature reconstructions for the end of the Pleistocene and the first half of the Holocene based on biotic proxies are rare for inland Europe around 49°N. We analysed a 7 m long sequence of lake deposits in the Vihorlat Mts in eastern Slovakia (820 m a.s.l.). Chironomid head capsules were used to reconstruct mean July temperature (TJuly), other proxies (diatoms, green algae, pollen, geochemistry) were used to reconstruct local environmental changes that might have affected the climate reconstruction, such as epilimnetic total phosphorus concentrations (TP), lake level changes and development of surrounding vegetation. During the Younger Dryas (YD), temperature fluctuated between 7 and 11 °C, with distinct, decadal to centennial scale variations, that agree with other palaeoclimate records in Europe such as δ18O content in stalagmites or Greenland ice cores. The results indicate that the site was somewhat colder than expected from the general south-to-north YD temperature gradient within Europe, possibly because of north-facing exposition. The warmer phases of the YD were characterised by low water level or even complete desiccation of the lake (12,200-12,400 cal yr BP). At the Late-Glacial/Holocene transition TJuly steeply increased from from 11 to 15.5 °C (11,700-11,400 cal yr BP) - the highest TJuly for entire sequence. This rapid climate change was reflected by all proxies as a compositional change and increasing species diversity. The open woodlands of Pinus, Betula, Larix and Picea were replaced by broad-leaved temperate forests dominated by Betula, later by Ulmus and finally by Corylus (ca 9700 cal yr BP). At the same time, input of eroded coarse-grained material into the lake decreased and organic matter (LOI) and biogenic silica increased. The Early-Holocene climate was rather stable till 8700 cal yr BP, with temporary decrease in TJuly around 11,200 cal yr BP. The lake was productive with a well-developed littoral, as indicated by both diatoms and chironomids. A distinct decline of TJuly to 10 °C between 8700 and 8000 cal yr BP was associated with decreasing chironomid diversity and increasing climate moistening indicated by pollen. Tychoplanktonic and phosphorus-demanding diatoms increased which might be explained by hydrological and land-cover changes. Later, a gradual warming started after 7000 cal yr BP and representation of macrophytes, periphytic diatoms and littoral chironomids increased. Our results suggest that the Holocene thermal maximum was taking place unusually early in the Holocene at our study site, but its timing might be affected by topography and mesoclimate. We further demonstrated that temperature changes had coincided with variations in local hydrology