Tracking the transcriptional host response from the acute to the regenerative phase of experimental pneumococcal meningitis

Despite the availability of effective antibiotic therapies, pneumococcal meningitis (PM) has a case fatality rate of up to 30% and causes neurological sequelae in up to half of the surviving patients. The underlying brain damage includes apoptosis of neurons in the hippocampus and necrosis in the cortex. Therapeutic options to reduce acute injury and to improve outcome from PM are severely limited.With the aim to develop new therapies a number of pharmacologic interventions have been evaluated. However, the often unpredictable outcome of interventional studies suggests that the current concept of the pathophysiologic events during bacterial meningitis is fragmentary. The aim of this work is to describe the transcriptomic changes underlying the complex mechanisms of the host response to pneumococcal meningitis in a temporal and spatial context using a well characterized infant rat model.

Functions of lipid raft membrane microdomains at the blood-brain barrier

The blood-brain barrier (BBB) is a highly specialized structural and functional component of the central nervous system that separates the circulating blood from the brain and spinal cord parenchyma. Brain endothelial cells (BECs) that primarily constitute the BBB are tightly interconnected by multiprotein complexes, the adherens junctions and the tight junctions, thereby creating a highly restrictive cellular barrier. Lipid-enriched membrane microdomain compartmentalization is an inherent property of BECs and allows for the apicobasal polarity of brain endothelium, temporal and spatial coordination of cell signaling events, and actin remodeling. In this manuscript, we review the role of membrane microdomains, in particular lipid rafts, in the BBB under physiological conditions and during leukocyte transmigration/diapedesis. Furthermore, we propose a classification of endothelial membrane microdomains based on their function, or at least on the function ascribed to the molecules included in such heterogeneous rafts: (1) rafts associated with interendothelial junctions and adhesion of BECs to basal lamina (scaffolding rafts); (2) rafts involved in immune cell adhesion and migration across brain endothelium (adhesion rafts); (3) rafts associated with transendothelial transport of nutrients and ions (transporter rafts).

Spatiotemporal dynamics: the need for an innovative approach in mountain hazard risk management

Starting with an overview on losses due to mountain hazards in the Russian Federation and the European Alps, the question is raised why a substantial number of events still are recorded—despite considerable efforts in hazard mitigation and risk reduction. The main reason for this paradox lies in a missing dynamic risk-based approach, and it is shown that these dynamics have different roots: firstly, neglecting climate change and systems dynamics, the development of hazard scenarios is based on the static approach of design events. Secondly, due to economic development and population dynamics, the elements at risk exposed are subject to spatial and temporal changes. These issues are discussed with respect to temporal and spatial demands. As a result, it is shown how risk is dynamic on a long-term and short-term scale, which has to be acknowledged in the risk concept if this concept is targeted at a sustainable development of mountain regions. A conceptual model is presented that can be used for dynamical risk assessment, and it is shown by different management strategies how this model may be converted into practice. Furthermore, the interconnectedness and interaction between hazard and risk are addressed in order to enhance prevention, the level of protection and the degree of preparedness.

A satellite-based snow cover climatology (1985–2011) for the European Alps derived from AVHRR data

Seasonal snow cover is of great environmental and socio-economic importance for the European Alps. Therefore a high priority has been assigned to quantifying its temporal and spatial variability. Complementary to land-based monitoring networks, optical satellite observations can be used to derive spatially comprehensive information on snow cover extent. For understanding long-term changes in alpine snow cover extent, the data acquired by the Advanced Very High Resolution Radiometer (AVHRR) sensors mounted onboard the National Oceanic and Atmospheric Association (NOAA) and Meteorological Operational satellite (MetOp) platforms offer a unique source of information. In this paper, we present the first space-borne 1 km snow extent climatology for the Alpine region derived from AVHRR data over the period 1985–2011. The objective of this study is twofold: first, to generate a new set of cloud-free satellite snow products using a specific cloud gap-filling technique and second, to examine the spatiotemporal distribution of snow cover in the European Alps over the last 27 yr from the satellite perspective. For this purpose, snow parameters such as snow onset day, snow cover duration (SCD), melt-out date and the snow cover area percentage (SCA) were employed to analyze spatiotemporal variability of snow cover over the course of three decades. On the regional scale, significant trends were found toward a shorter SCD at lower elevations in the south-east and south-west. However, our results do not show any significant trends in the monthly mean SCA over the last 27 yr. This is in agreement with other research findings and may indicate a deceleration of the decreasing snow trend in the Alpine region. Furthermore, such data may provide spatially and temporally homogeneous snow information for comprehensive use in related research fields (i.e., hydrologic and economic applications) or can serve as a reference for climate models.

Microcystic macular edema: retrograde maculopathy caused by optic neuropathy

PURPOSE To investigate retrograde axonal degeneration for its potential to cause microcystic macular edema (MME), a maculopathy that has been previously described in patients with demyelinating disease. To identify risk factors for MME and to expand the anatomic knowledge on MME. DESIGN Retrospective case series. PARTICIPANTS We included 117 consecutive patients and 180 eyes with confirmed optic neuropathy of variable etiology. Patients with glaucoma were excluded. METHODS We determined age, sex, visual acuity, etiology of optic neuropathy, and the temporal and spatial characteristics of MME. Eyes with MME were compared with eyes with optic neuropathy alone and to healthy fellow eyes. With retinal layer segmentation we quantitatively measured the intraretinal anatomy. MAIN OUTCOME MEASURES Demographic data, distribution of MME in the retina, and thickness of retinal layers were analyzed. RESULTS We found MME in 16 eyes (8.8%) from 9 patients, none of whom had multiple sclerosis or neuromyelitis optica. The MME was restricted to the inner nuclear layer (INL) and had a characteristic perifoveal circular distribution. Compared with healthy controls, MME was associated with significant thinning of the ganglion cell layer and nerve fiber layer, as well as a thickening of the INL and the deeper retinal layers. Youth is a significant risk factor for MME. CONCLUSIONS Microcystic macular edema is not specific for demyelinating disease. It is a sign of optic neuropathy irrespective of its etiology. The distinctive intraretinal anatomy suggests that MME is caused by retrograde degeneration of the inner retinal layers, resulting in impaired fluid resorption in the macula.

Searching the Rhone delta channel in Lake Geneva since François‐Alphonse Forel

In the late 19th century, F.A. FOREL led investigations of the Rhone River delta area of Lake Geneva that resulted in the dis- covery of a textbook example of a river-fed delta system containing impressive subaquatic channels. Well ahead of the marine counterparts, scientific observations and interpretations of water currents shaping the delta edifice for the first time documented how underflow currents carry cold, suspension-laden waters from the river mouth all the way to the deep basin. These early investigations of the Rhone delta laid the basis for follow-up studies in the 20th and 21th centuries. Sediment coring, water-column measurements, manned submersible diving, seismic reflection profiling and bathymetric sur- veying eventually provided a rich database to unravel the key erosional and depositional processes, further documenting the impact of human-induced changes in the catchment. With the merging of old and new scientific knowledge, today a comprehensive understanding prevails of how a delta changes through time, how its channels are formed, and what potential natural hazards may be related to its evolution. New and efficient bathymetric techniques, paired with novel coring operations, provided a time-series of morphologic evolution showing and quantifying the high dynamics of the delta/channel evolution in an unprecedented temporal and spatial reso- lution. Future investigations will continue to further quantify these dynamic processes and to link the evolution of the subaquatic domain with changes and processes in the catchment and with natural hazards. Its size, easy access, and large variety of states and processes will continue to make the Rhone delta area a perfect ‘laboratory’ in which general processes can be studied that could be upscaled or downscaled to other marine and lacustrine deltas.

From Broadstone to Zackenberg

Ecological networks are typically complex constructions of species and their interactions. During the last decade, the study of networks has moved from static to dynamic analyses, and has attained a deeper insight into their internal structure, heterogeneity, and temporal and spatial resolution. Here, we review, discuss and suggest research lines in the study of the spatio-temporal heterogeneity of networks and their hierarchical nature. We use case study data from two well-characterized model systems (the food web in Broadstone Stream in England and the pollination network at Zackenberg in Greenland), which are complemented with additional information from other studies. We focus upon eight topics: temporal dynamic space-for-time substitutions linkage constraints habitat borders network modularity individual-based networks invasions of networks and super networks that integrate different network types. Few studies have explicitly examined temporal change in networks, and we present examples that span from daily to decadal change: a common pattern that we see is a stable core surrounded by a group of dynamic, peripheral species, which, in pollinator networks enter the web via preferential linkage to the most generalist species. To some extent, temporal and spatial scales are interchangeable (i.e. networks exhibit ‘ergodicity’) and we explore how space-for-time substitutions can be used in the study of networks. Network structure is commonly constrained by phenological uncoupling (a temporal phenomenon), abundance, body size and population structure. Some potential links are never observed, that is they are ‘forbidden’ (fully constrained) or ‘missing’ (a sampling effect), and their absence can be just as ecologically significant as their presence. Spatial habitat borders can add heterogeneity to network structure, but their importance has rarely been studied: we explore how habitat generalization can be related to other resource dimensions. Many networks are hierarchically structured, with modules forming the basic building blocks, which can result in self-similarity. Scaling down from networks of species reveals another, finer-grained level of individual-based organization, the ecological consequences of which have yet to be fully explored. The few studies of individual-based ecological networks that are available suggest the potential for large intraspecific variance and, in the case of food webs, strong size-structuring. However, such data are still scarce and more studies are required to link individual-level and species-level networks. Invasions by alien species can be tracked by following the topological ‘career’ of the invader as it establishes itself within a network, with potentially important implications for conservation biology. Finally, by scaling up to a higher level of organization, it is possible to combine different network types (e.g. food webs and mutualistic networks) to form super networks, and this new approach has yet to be integrated into mainstream ecological research. We conclude by listing a set of research topics that we see as emerging candidates for ecological network studies in the near future.

Correction of dephasing oscillations in matter-wave interferometry

Vibrations, electromagnetic oscillations, and temperature drifts are among the main reasons for dephasing in matter-wave interferometry. Sophisticated interferometry experiments, e.g., with ions or heavy molecules, often require integration times of several minutes due to the low source intensity or the high velocity selection. Here we present a scheme to suppress the influence of such dephasing mechanisms—especially in the low-frequency regime—by analyzing temporal and spatial particle correlations available in modern detectors. Such correlations can reveal interference properties that would otherwise be washed out due to dephasing by external oscillating signals. The method is shown experimentally in a biprism electron interferometer where a perturbing oscillation is artificially introduced by a periodically varying magnetic field. We provide a full theoretical description of the particle correlations where the perturbing frequency and amplitude can be revealed from the disturbed interferogram. The original spatial fringe pattern without the perturbation can thereby be restored. The technique can be applied to lower the general noise requirements in matter-wave interferometers. It allows for the optimization of electromagnetic shielding and decreases the efforts for vibrational or temperature stabilization.

Continuous dynamic mapping of the corticospinal tract during surgery of motor eloquent brain tumors: evaluation of a new method

OBJECT The authors developed a new mapping technique to overcome the temporal and spatial limitations of classic subcortical mapping of the corticospinal tract (CST). The feasibility and safety of continuous (0.4-2 Hz) and dynamic (at the site of and synchronized with tissue resection) subcortical motor mapping was evaluated. METHODS The authors prospectively studied 69 patients who underwent tumor surgery adjacent to the CST (< 1 cm using diffusion tensor imaging and fiber tracking) with simultaneous subcortical monopolar motor mapping (short train, interstimulus interval 4 msec, pulse duration 500 μsec) and a new acoustic motor evoked potential alarm. Continuous (temporal coverage) and dynamic (spatial coverage) mapping was technically realized by integrating the mapping probe at the tip of a new suction device, with the concept that this device will be in contact with the tissue where the resection is performed. Motor function was assessed 1 day after surgery, at discharge, and at 3 months. RESULTS All procedures were technically successful. There was a 1:1 correlation of motor thresholds for stimulation sites simultaneously mapped with the new suction mapping device and the classic fingerstick probe (24 patients, 74 stimulation points; r(2) = 0.98, p < 0.001). The lowest individual motor thresholds were as follows: > 20 mA, 7 patients; 11-20 mA, 13 patients; 6-10 mA, 8 patients; 4-5 mA, 17 patients; and 1-3 mA, 24 patients. At 3 months, 2 patients (3%) had a persistent postoperative motor deficit, both of which were caused by a vascular injury. No patient had a permanent motor deficit caused by a mechanical injury of the CST. CONCLUSIONS Continuous dynamic mapping was found to be a feasible and ergonomic technique for localizing the exact site of the CST and distance to the motor fibers. The acoustic feedback and the ability to stimulate the tissue continuously and exactly at the site of tissue removal improves the accuracy of mapping, especially at low (< 5 mA) stimulation intensities. This new technique may increase the safety of motor eloquent tumor surgery.

Serosurveillance of Schmallenberg virus in Switzerland using bulk tank milk samples.

Infections with Schmallenberg virus (SBV), a novel Orthobunyavirus transmitted by biting midges, can cause abortions and malformations of newborns and severe symptoms in adults of domestic and wild ruminants. Understanding the temporal and spatial distribution of the virus in a certain territory is important for the control and prevention of the disease. In this study, seroprevalence of antibodies against SBV and the spatial spread of the virus was investigated in Swiss dairy cattle applying a milk serology technique on bulk milk samples. The seroprevalence in cattle herds was significantly higher in December 2012 (99.5%) compared to July 2012 (19.7%). This high between-herd seroprevalence in cattle herds was observed shortly after the first detection of viral infections. Milk samples originating from farms with seropositive animals taken in December 2012 (n=209; mean 160%) revealed significantly higher S/P% ratios than samples collected in July 2012 (n=48; mean 103.6%). This finding suggests a high within-herd seroprevalence in infected herds which makes testing of bulk tank milk samples for the identification farms with past exposures to SBV a sensitive method. It suggests also that within-herd transmission followed by seroconversion still occurred between July and December. In July 2012, positive bulk tank milk samples were mainly restricted to the western part of Switzerland whereas in December 2012, all samples except one were positive. A spatial analysis revealed a separation of regions with and without positive farms in July 2012 and no spatial clustering within the regions with positive farms. In contrast to the spatial dispersion of bluetongue virus, a virus that is also transmitted by Culicoides midges, in 2008 in Switzerland, the spread of SBV occurred from the western to the eastern part of the country. The dispersed incursion of SBV took place in the western part of Switzerland and the virus spread rapidly to the remaining territory. This spatial pattern is consistent with the hypothesis that transmission by Culicoides midges was the main way of spreading.

Characterization of surface winds over the Iberian Peninsula

This work presents a characterization of the surface wind climatology over the Iberian Peninsula (IP). For this objective, an unprecedented observational database has been developed. The database covers a period of 6years (2002–2007) and consists of hourly wind speed and wind direction data recorded at 514 automatic weather stations. Theoriginal observations underwent a quality control process to remove rough errors from the data set. In the first step, the annual and seasonal mean behaviour of the wind field are presented. This analysis shows the high spatial variability of the wind as a result of its interaction with the main orographic features of the IP. In order to simplify the characterization of the wind, a clustering procedure was applied to group the observational sites with similar temporal wind variability. A total of 20 regions are identified. These regions are strongly related to the main landforms of the IP. The wind behaviour of each region, characterized by the wind rose (WR), annual cycle (AC) and wind speed histogram, is explained as the response of each region to the main circulation types (CTs) affecting the IP. Results indicate that the seasonal variability of the synoptic scale is related with intra-annual variability and modulated by local features in the WRs variability. The wind speed distribution not always fit to a unimodal Weibull distribution consequence of interactions at different atmospheric scales. This work contributes to a deeper understanding of the temporal and spatial variability of surface winds. Taken together, the wind database created, the methodology used and the conclusion extracted are a benchmark for future works based on the wind behaviour.

The deglaciation history of the Simplon region (southern Swiss Alps) constrained by 10Be exposure dating of ice-molded bedrock surfaces

The deglaciation history of the Swiss Alps after the Last Glacial Maximum involved the decay of several ice domes and the subsequent disintegration of valley glaciers at high altitude. Here we use bedrock exposure dating to reconstruct the temporal and spatial pattern of ice retreat at the Simplon Pass (altitude: ∼2000 m) located 40 km southwest of the ‘Rhône ice dome’. Eleven 10Be exposure ages from glacially polished quartz veins and ice-molded bedrock surfaces cluster tightly between 13.5 ± 0.6 ka and 15.4 ± 0.6 ka (internal errors) indicating that the Simplon Pass depression became ice-free at 14.1 ± 0.4 ka (external error of mean age). This age constraint is interpreted to record the melting of the high valley glaciers in the Simplon Pass region during the warm Bølling–Allerød interstadial shortly after the Oldest Dryas stadial. Two bedrock samples collected a few hundred meters above the pass depression yield older 10Be ages of 17.8 ± 0.6 ka and 18.0 ± 0.6 ka. These ages likely reflect the initial downwasting of the Rhône ice dome and the termination of the ice transfluence from the ice dome across the Simplon Pass toward the southern foreland. There, the retreat of the piedmont glacier in Val d’Ossola was roughly synchronous with the decay of the Rhône ice dome in the interior of the mountain belt, as shown by 10Be ages of 17.7 ± 0.9 ka and 16.1 ± 0.6 ka for a whaleback at ∼500 m elevation near Montecrestese in northern Italy. In combination with well-dated paleoclimate records derived from lake sediments, our new age data suggest that during the deglaciation of the European Alps the decay of ice domes was approximately synchronous with the retreat of piedmont glaciers in the foreland and was followed by the melting of high-altitude valley glaciers after the transition from the Oldest Dryas to the Bølling–Allerød, when mean annual temperatures rose rapidly by ∼3 °C.

Dynamic changes of intramural hematoma in patients with acute spontaneous internal carotid artery dissection.

BACKGROUND We prospectively investigated temporal and spatial evolution of intramural hematomas in patients with acute spontaneous internal carotid artery dissection using repeated magnetic resonance imaging over six-months. AIM The aim of the present study was to assess dynamic changes of intramural hematoma in patients with acute spontaneous internal carotid artery dissection at multiple follow-up time-points with T1w, PD/T2w, and magnetic resonance angiography. METHODS We performed serial multiparametric magnetic resonance imaging in 10 patients with spontaneous internal carotid artery dissection on admission, at days 1, 3, 7-14 and at months 1·5, 3, and 6. We calculated the volume and extension of the hyperintense intramural hematoma using T1w and PD/T2w fat suppressed sequences and assessed the degree of stenosis due to the hematoma using magnetic resonance angiography. RESULTS Mean interval from symptom onset to first magnetic resonance imaging was two-days (SD 2·7). Two patients presented with ischemic stroke, three with transient ischemic attacks, and five with pain and local symptoms only. Nine patients had a transient increase of the intramural hematoma volume, mainly up to day 10 after symptom onset. Fifty percent had a transient increase in the degree of the internal carotid artery stenosis on MRA, one resulting in a temporary occlusion. Lesions older than one-week were predominantly characterized by a shift from iso- to hyperintese signal on T2w images. At three-month follow-up, intramural hematoma was no longer detectable in 80% of patients and had completely resolved in all patients after six-months. CONCLUSIONS Spatial and temporal dynamics of intramural hematomas after spontaneous internal carotid artery dissection showed an early volume increase with concomitant progression of the internal carotid artery stenosis in 5 of 10 patients. Although spontaneous internal carotid artery dissection overall carries a good prognosis with spontaneous hematoma resorption in all our patients, early follow-up imaging may be considered, especially in case of new clinical symptoms.

Landscape mosaics maps as a basis for spatial assessment and negotiation of ecosystem services and their trade-offs at the meso-scale: Examples from Laos, Madagascar and China

Mapping ecosystem services (ES) and their trade-offs is a key requirement for informed decision making for land use planning and management of natural resources that aim to move towards increasing the sustainability of landscapes. The negotiations of the purposes of landscapes and the services they should provide are difficult as there is an increasing number of stakeholders active at different levels with a variety of interests present on one particular landscape.Traditionally, land cover data is at the basis for mapping and spatial monitoring of ecosystem services. In light of complex landscapes it is however questionable whether land cover per se and as a spatial base unit is suitable for monitoring and management at the meso-scale. Often the characteristics of a landscape are defined by prevalence, composition and specific spatial and temporal patterns of different land cover types. The spatial delineation of shifting cultivation agriculture represents a prominent example of a land use system with its different land use intensities that requires alternative methodologies that go beyond the common remote sensing approaches of pixel-based land cover analysis due to the spatial and temporal dynamics of rotating cultivated and fallow fields.Against this background we advocate that adopting a landscape perspective to spatial planning and decision making offers new space for negotiation and collaboration, taking into account the needs of local resource users, and of the global community. For this purpose we introduce landscape mosaicsdefined as new spatial unit describing generalized land use types. Landscape mosaics have allowed us to chart different land use systems and land use intensities and permitted us to delineate changes in these land use systems based on changes of external claims on these landscapes. The underlying idea behindthe landscape mosaics is to use land cover data typically derived from remote sensing data and to analyse and classify spatial patterns of this land cover data using a moving window approach. We developed the landscape mosaics approach in tropical, forest dominated landscapesparticularly shifting cultivation areas and present examples ofour work from northern Laos, eastern Madagascarand Yunnan Province in China.

Species Richness-Environment Relationships of European Arthropods at Two Spatial Grains: Habitats and Countries

We study how species richness of arthropods relates to theories concerning net primary productivity, ambient energy, water-energy dynamics and spatial environmental heterogeneity. We use two datasets of arthropod richness with similar spatial extents (Scandinavia to Mediterranean), but contrasting spatial grain (local habitat and country). Samples of ground-dwelling spiders, beetles, bugs and ants were collected from 32 paired habitats at 16 locations across Europe. Species richness of these taxonomic groups was also determined for 25 European countries based on the Fauna Europaea database. We tested effects of net primary productivity (NPP), annual mean temperature (T), annual rainfall (R) and potential evapotranspiration of the coldest month (PETmin) on species richness and turnover. Spatial environmental heterogeneity within countries was considered by including the ranges of NPP, T, R and PETmin. At the local habitat grain, relationships between species richness and environmental variables differed strongly between taxa and trophic groups. However, species turnover across locations was strongly correlated with differences in T. At the country grain, species richness was significantly correlated with environmental variables from all four theories. In particular, species richness within countries increased strongly with spatial heterogeneity in T. The importance of spatial heterogeneity in T for both species turnover across locations and for species richness within countries suggests that the temperature niche is an important determinant of arthropod diversity. We suggest that, unless climatic heterogeneity is constant across sampling units, coarse-grained studies should always account for environmental heterogeneity as a predictor of arthropod species richness, just as studies with variable area of sampling units routinely consider area.