Synchronization and desynchronization in epilepsy: controversies and hypotheses

Epilepsy has been historically seen as a functional brain disorder associated with excessive synchronization of large neuronal populations leading to a hypersynchronous state. Recent evidence showed that epileptiform phenomena, particularly seizures, result from complex interactions between neuronal networks characterized by heterogeneity of neuronal firing and dynamical evolution of synchronization. Desynchronization is often observed preceding seizures or during their early stages; in contrast, high levels of synchronization observed towards the end of seizures may facilitate termination. In this review we discuss cellular and network mechanisms responsible for such complex changes in synchronization. Recent work has identified cell-type-specific inhibitory and excitatory interactions, the dichotomy between neuronal firing and the non-local measurement of local field potentials distant to that firing, and the reflection of the neuronal dark matter problem in non-firing neurons active in seizures. These recent advances have challenged long-established views and are leading to a more rigorous and realistic understanding of the pathophysiology of epilepsy.

Search for new phenomena in events with three charged leptons at a center-of-mass energy of 7 TeV with the ATLAS detector

A generic search for anomalous production of events with at least three charged leptons is presented. The search uses a pp-collision data sample at a center-of-mass energy of root s = 7 TeV corresponding to 4.6 fb(-1) of integrated luminosity collected in 2011 by the ATLAS detector at the CERN Large Hadron Collider. Events are required to contain at least two electrons or muons, while the third lepton may either be an additional electron or muon, or a hadronically decaying tau lepton. Events are categorized by the presence or absence of a reconstructed tau-lepton or Z-boson candidate decaying to leptons. No significant excess above backgrounds expected from Standard Model processes is observed. Results are presented as upper limits on event yields from non-Standard-Model processes producing at least three prompt, isolated leptons, given as functions of lower bounds on several kinematic variables. Fiducial efficiencies for model testing are also provided. The use of the results is illustrated by setting upper limits on the production of doubly charged Higgs bosons decaying to same-sign lepton pairs.

Biotic resistance to plant invasion in grassland: Does seed predation increase with resident plant diversity?

Seed predation impacts heavily on plant populations and community composition in grasslands. In particular, generalist seed predators may contribute to biotic resistance, i.e. the ability of resident species in a community to reduce the success of non-indigenous plant invaders. However, little is known of predators' preferences for seeds of indigenous or non-indigenous plant species or how seed predation varies across communities. We hypothesize that seed predation does not differ between indigenous and non-indigenous plant species and that seed predation is positively related to plant species diversity in the resident community. The seed removal of 36 indigenous and non-indigenous grassland species in seven extensively or intensively managed hay meadows across Switzerland covering a species-richness gradient of 18-50 plant species per unit area (c. 2 m(2)) was studied. In mid-summer 2011, c. 24,000 seeds were exposed to predators in Petri dishes filled with sterilized soil, and the proportions of seeds removed were determined after three days' exposure. These proportions varied among species (9.2-62.5%) and hay meadows (17.8-48.6%). Seed removal was not related to seed size. Moreover, it did not differ between indigenous and non-indigenous species, suggesting that mainly generalist seed predators were active. However, seed predation was positively related to plant species richness across a gradient in the range of 18-38 species per unit area, representing common hay meadows in Switzerland. Our results suggest that generalist post-dispersal seed predation contributes to biotic resistance and may act as a filter to plant invasion by reducing the propagule pressure of non-local plant species.

Mobilities and Pottery Production Archaeological and Anthropological Perspectives

Our workshop aims at a deeper understanding of various itineraries of pottery and dif-ferent forms of human mobilities in which pottery is relevant, bringing together archae-ological and anthropological perspectives. For thousands of years, pottery has been an important part of many societies’ material culture and therefore a major research topic in both disciplines. In past and present societies the material existence of ceramic vessels is informed by various movements across time and space but also by periods of stasis: from the mo-ment of their production until their exclusion from daily practices, either disposed as waste, excluded as funerary objects or stored as collectibles. In their seemingly endless material durability, ceramic vessels might outlive their human producers, distributors or consumers and travel farther and longer. Still they are embedded in the regimes of human mobility, ranging from daily subsistence-based mobility to long-term migrations. In such processes, pottery shifts between spatial, temporal, social, economic and cultural contexts. Thereby ceramic vessels are appropriated and integrated in new contexts of action and meaning, sometimes leading to material transformations. This workshop takes place in the context of our archaeological research project „Mobili-ties, Entanglements and Transformations in Neolithic Societies on the Swiss Plateau (3900-3500 BC)“ to which our PhDs are connected. We address the above outlined topic by analysing the production of pottery. Based on dendrochronologically dated settle-ments between 3900 and 3500 BC, two regional pottery styles and their local variations are well known, Pfyn and Cortaillod. The vessels share the same habitus and were made of clays and temper deriving from the settlements’ surroundings. However, some vessels specific to other pottery styles are also present on the sites. They are characteristic for pottery styles known from more or less far off regions (Michelsberg, Munzingen or Néo-lithique Moyen Bourguignon). Some of them were travelling objects, as their non local raw materials show. Others seem to have been produced locally, pointing to long-term mobility and a change of residence from neighbouring social groups.

Search for microscopic black holes and string balls in final states with leptons and jets with the ATLAS detector at √s = 8 TeV

A search for an excess of events with multiple high transverse momentum objects including charged leptons and jets is presented, using 20.3 fb−1 of proton-proton collision data recorded by the ATLAS detector at the Large Hadron Collider in 2012 at a centre-of-mass energy of √s = 8TeV. No excess of events beyond Standard Model expectations is observed. Using extra-dimensional models for black hole and string ball production and decay, exclusion contours are determined as a function of the mass threshold for production and the fundamental gravity scale for two, four and six extra dimensions. For six extra dimensions, mass thresholds of 4.8–6.2TeV are excluded at 95% confidence level, depending on the fundamental gravity scale and model assumptions. Upper limits on the fiducial cross-sections for non-Standard Model production of these final states are set.

Numerical corrections to the strong coupling effective Polyakov-line action for finite T Yang-Mills theory

We consider a three-dimensional effective theory of Polyakov lines derived previously from lattice Yang-Mills theory and QCD by means of a resummed strong coupling expansion. The effective theory is useful for investigations of the phase structure, with a sign problem mild enough to allow simulations also at finite density. In this work we present a numerical method to determine improved values for the effective couplings directly from correlators of 4d Yang-Mills theory. For values of the gauge coupling up to the vicinity of the phase transition, the dominant short range effective coupling are well described by their corresponding strong coupling series. We provide numerical results also for the longer range interactions, Polyakov lines in higher representations as well as four-point interactions, and discuss the growing significance of non-local contributions as the lattice gets finer. Within this approach the critical Yang-Mills coupling β c is reproduced to better than one percent from a one-coupling effective theory on N τ = 4 lattices while up to five couplings are needed on N τ = 8 for the same accuracy.

Deep Points Consolidation

In this paper, we present a consolidation method that is based on a new representation of 3D point sets. The key idea is to augment each surface point into a deep point by associating it with an inner point that resides on the meso-skeleton, which consists of a mixture of skeletal curves and sheets. The deep points representation is a result of a joint optimization applied to both ends of the deep points. The optimization objective is to fairly distribute the end points across the surface and the meso-skeleton, such that the deep point orientations agree with the surface normals. The optimization converges where the inner points form a coherent meso-skeleton, and the surface points are consolidated with the missing regions completed. The strength of this new representation stems from the fact that it is comprised of both local and non-local geometric information. We demonstrate the advantages of the deep points consolidation technique by employing it to consolidate and complete noisy point-sampled geometry with large missing parts.

Hormone therapy and physical activity as predictors of lung cancer risk and survival: The California Teachers Study

Cigarette smoking is responsible for the majority of lung cancer cases worldwide; however, a proportion of never smokers still develop lung cancer over their lifetime, prompting investigation into additional factors that may modify lung cancer incidence, as well as mortality. Although hormone therapy (HT), physical activity (PA), and lung cancer have been previously examined, the associations remain unclear. This study investigated exposure to HT and PA that may modulate underlying mechanisms of lung cancer etiology and progression among women by using existing, de-identified data from the California Teachers Study (CTS).^ The CTS cohort, established in 1995–1996, has 133,479 active and retired female teachers and administrators, recruited through the California State Teachers Retirement System, and followed annually for cancer diagnosis, death, and change of address. Each woman enrolled in the CTS returned a questionnaire covering a wide variety of issues related to cancer risk and women's health, including recent and past HT use and physical activity, as well as active and environmental cigarette smoke exposure. Complete data to assess the associations between HT and lung cancer risk and survival were available for 60,592 postmenopausal women. Between 1995 and 2007, 727 of these women were diagnosed with invasive lung cancer; 441 of these died. Complete data to assess the associations between PA and lung cancer risk and survival were available for 118,513 women. Between 1995 and 2007, 853 of these women were diagnosed with invasive lung cancer; 516 of these died.^ After careful adjustment for smoking habits and other potential confounders, no measure of HT use was associated with lung cancer risk; however, any HT use (vs. no use) was associated with a decrease in lung-cancer-specific mortality. Specifically, among women who only used estrogen (E-only), decreases in lung cancer mortality were seen for recent use, but not for former use; no association was observed for estrogen plus progestin (E+P). Furthermore, among former users of HT, a statistically significant decrease in lung cancer mortality was observed for E-only use within 5 years prior to baseline, but not for E-only use >5 years prior to baseline. Neither long-term recreational PA nor recent recreational PA alone were associated with lung cancer risk; however, among women with a BMI<25 and ever smokers, high long-term moderate+strenuous PA was associated with a decrease in lung cancer risk. Women with non-local disease showed a decrease in lung cancer mortality associated with increasing duration of strenuous long-term activity, and 1.50-3.00 h/wk/y of recent moderate or recent strenuous PA. Long-term moderate PA was associated with decreased lung cancer mortality in never smokers, whereas recent moderate PA was associated with increased lung cancer mortality in current smokers. ^ Placing our findings in the context of the current literature, HT does not appear to be associated with lung cancer risk and previous studies reporting a protective effect of HT use on lung cancer risk may be subject to residual confounding by smoking. Looking at our findings regarding PA overall, the evidence still remains inconclusive regarding whether or not physical activity influence lung cancer risk or mortality. Our results suggest that recreational PA may associated with decreased lung cancer risk among women with BMI<25 and ever smoking-women; however, residual confounding by smoking should be strongly considered. To our knowledge, this is the first study to investigate lifetime recreational PA and lung cancer mortality among women. Our results contribute to the growing body of knowledge regarding non-smoking-related risk factors for lung cancer incidence and mortality among women. Given the potential clinical and interventional significance, further study and validation of these findings is warranted.^

Logistic regression with Markov chains as covariates

The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is an obvious carcinogen for lung cancer. Since CBMN (Cytokinesis-blocked micronucleus) has been found to be extremely sensitive to NNK-induced genetic damage, it is a potential important factor to predict the lung cancer risk. However, the association between lung cancer and NNK-induced genetic damage measured by CBMN assay has not been rigorously examined. ^ This research develops a methodology to model the chromosomal changes under NNK-induced genetic damage in a logistic regression framework in order to predict the occurrence of lung cancer. Since these chromosomal changes were usually not observed very long due to laboratory cost and time, a resampling technique was applied to generate the Markov chain of the normal and the damaged cell for each individual. A joint likelihood between the resampled Markov chains and the logistic regression model including transition probabilities of this chain as covariates was established. The Maximum likelihood estimation was applied to carry on the statistical test for comparison. The ability of this approach to increase discriminating power to predict lung cancer was compared to a baseline "non-genetic" model. ^ Our method offered an option to understand the association between the dynamic cell information and lung cancer. Our study indicated the extent of DNA damage/non-damage using the CBMN assay provides critical information that impacts public health studies of lung cancer risk. This novel statistical method could simultaneously estimate the process of DNA damage/non-damage and its relationship with lung cancer for each individual.^

New methods for quantification and analysis of quantitative real-time polymerase chain reaction data

Quantitative real-time polymerase chain reaction (qPCR) is a sensitive gene quantitation method that has been widely used in the biological and biomedical fields. The currently used methods for PCR data analysis, including the threshold cycle (CT) method, linear and non-linear model fitting methods, all require subtracting background fluorescence. However, the removal of background fluorescence is usually inaccurate, and therefore can distort results. Here, we propose a new method, the taking-difference linear regression method, to overcome this limitation. Briefly, for each two consecutive PCR cycles, we subtracted the fluorescence in the former cycle from that in the later cycle, transforming the n cycle raw data into n-1 cycle data. Then linear regression was applied to the natural logarithm of the transformed data. Finally, amplification efficiencies and the initial DNA molecular numbers were calculated for each PCR run. To evaluate this new method, we compared it in terms of accuracy and precision with the original linear regression method with three background corrections, being the mean of cycles 1-3, the mean of cycles 3-7, and the minimum. Three criteria, including threshold identification, max R2, and max slope, were employed to search for target data points. Considering that PCR data are time series data, we also applied linear mixed models. Collectively, when the threshold identification criterion was applied and when the linear mixed model was adopted, the taking-difference linear regression method was superior as it gave an accurate estimation of initial DNA amount and a reasonable estimation of PCR amplification efficiencies. When the criteria of max R2 and max slope were used, the original linear regression method gave an accurate estimation of initial DNA amount. Overall, the taking-difference linear regression method avoids the error in subtracting an unknown background and thus it is theoretically more accurate and reliable. This method is easy to perform and the taking-difference strategy can be extended to all current methods for qPCR data analysis.^

Intensive care unit utilization among patients with cancer at the end of life

Over the last 2 decades, survival rates in critically ill cancer patients have improved. Despite the increase in survival, the intensive care unit (ICU) continues to be a location where end-of-life care takes place. More than 20% of deaths in the United States occur after admission to an ICU, and as baby boomers reach the seventh and eighth decades of their lives, the volume of patients in the ICU is predicted to rise. The aim of this study was to evaluate intensive care unit utilization among patients with cancer who were at the end of life. End of life was defined using decedent and high-risk cohort study designs. The decedent study evaluated characteristics and ICU utilization during the terminal hospital stay among patients who died at The University of Texas MD Anderson Cancer Center during 2003-2007. The high-risk cohort study evaluated characteristics and ICU utilization during the index hospital stay among patients admitted to MD Anderson during 2003-2007 with a high risk of in-hospital mortality. Factors associated with higher ICU utilization in the decedent study included non-local residence, hematologic and non-metastatic solid tumor malignancies, malignancy diagnosed within 2 months, and elective admission to surgical or pediatric services. Having a palliative care consultation on admission was associated with dying in the hospital without ICU services. In the cohort of patients with high risk of in-hospital mortality, patients who went to the ICU were more likely to be younger, male, with newly diagnosed non-metastatic solid tumor or hematologic malignancy, and admitted from the emergency center to one of the surgical services. A palliative care consultation on admission was associated with a decreased likelihood of having an ICU stay. There were no differences in ethnicity, marital status, comorbidities, or insurance status between patients who did and did not utilize ICU services. Inpatient mortality probability models developed for the general population are inadequate in predicting in-hospital mortality for patients with cancer. The following characteristics that differed between the decedent study and high-risk cohort study can be considered in future research to predict risk of in-hospital mortality for patients with cancer: ethnicity, type and stage of malignancy, time since diagnosis, and having advance directives. Identifying those at risk can precipitate discussions in advance to ensure care remains appropriate and in accordance with the wishes of the patient and family.^

Isotopic composition of strontium in planktonic foraminiferas from sediments of the DSDP Holes 90-588 and 94-607

Measurements of 87Sr/86Sr on samples of planktonic foraminifers were used to reconstruct changes in the Sr isotopic composition of seawater for the past 8 Ma. The late Neogene was marked by a general, but not regular, increase in 87S/86Sr with two breaks in slope at 5.5 and 2.5 Ma. These times mark the beginning of two periods of steep increase in 87Sr/86Sr values, relative to preceding periods characterized by essentially constant values. During the last 2.5 Ma, 87Sr/86Sr values increased at an average rate of 0.000054/Ma. This steep increase suggests that the modem ocean is not in Sr isotopic equilibrium relative to its major input fluxes. A non-equilibrium model for the modern Sr budget suggests that the residence time of Sr is ~2.5 Ma, which is significantly less than previously accepted estimates of 4-5 Ma. Modelling results suggest that the increase in 87Sr/86Sr over the past 8 Ma could have resulted from a 25% increase in the riverine flux of Sr or an increase in the average 87Sr/86Sr of this flux by 0.0006. The dominant cause of increasing 87Sr/86Sr values of seawater during the late Neogene is believed to be increased rates of uplift and chemical weathering of mountainous regions. Calculations suggest that uplift and weathering of the Himalayan-Tibetan region alone can account for the majority of the observed 87Sr/86Sr increase since the early Late Miocene. Exhumation of Precambrian shield areas by continental ice-sheets may have contributed secondarily to accelerated mechanical and chemical weathering of old crustal silicates with high 87Sr/86Sr values. In fact, the upturn in 87Sr/86Sr at 2.5 Ma coincides with increased glacial activity in the Northern Hemisphere. A variety of geochemical (87Sr/86Sr, Ge/Si, d13C, CCD, etc.) and sedimentologic data (accumulation rates) from the marine sedimentary record are compatible with a progressive increase in the chemical weathering rate of continents and dissolved riverine fluxes during the late Cenozoic. We hypothesize that chemical weathering of the continents and dissolved riverine fluxes to the oceans reached a maximum during the late Pleistocene because of repeated glaciations, increased continental exposure by lowered sea level, and increased continental relief resulting from high rates of tectonism.

Lead 210 concentrations in sediments of the Arabian Sea

In order to evaluate bioturbation in abyssal Arabian-Sea sediments of the Indus fan profiles of 210Pb (half-life: 22.3 yr) and 234Th (half-life: 24.1 d) were measured in cores collected during September and October 1995 and April 1997, respectively. The density and composition of epibenthic megafauna and lebensspuren were determined in vertical seafloor photographs during April 1997. Mean eddy-diffusive mixing coefficients according to the distribution of excess 210Pb ( 210Pb-DB) were 0.072±0.028, 0.068±0.055, 0.373±0.119, 0.037±0.009 and 0.079±0.119 cm**2 yr**-1 in the northern, western, central, eastern and southern abyssal Arabian sea, respectively. Mean eddy-diffusive mixing coefficients according to the distribution of excess 234Th (234Th-DB) were 0.53, 1.64 and 0.47 cm**2 yr**-1 in the northern, western and central abyssal Arabian Sea, respectively. Mobile epibenthic megafauna at the western, northern, central and southern study sites were dominated by ophiuroids, holothurians, ophiuroids and natant decapods (the respective densities were 100, 82, 29 and 6 individuals 1000 m**-2). The northern study site was characterized by a high abundance of spoke traces and fecal casts. The central site showed spoke traces and many tracks. The southern site displayed the highest abundance of spoke traces, whereas at the western site hardly any lebensspuren were observed. There is evidence for at least two functional endmember communities in the Arabian Sea. In the northwestern Arabian Sea (WAST) vertical particle displacement seems to be dominated by macrofauna and primarily eddy-diffusive. In the southern Arabian Sea (SAST) non-local and 'incidental' mixing due to spoke-trace producers might become more important and superimpose reduced eddy-diffusive mixing. With respect to biological data CAST is an intermediate location. Given the biological data, average 210Pb-DB is higher and decimeter-scale variability of 210Pb-DB smaller at CAST than expected. These findings indicate that in a mixture of both endmember communities the organisms may interact in way that increases values of biodiffusivity, as reflected by 210Pb-DB, and reduces decimeter-scale 210Pb-DB heterogeneity in comparison to the simple sum of the isolated effects of the endmembers. For time scales <100 years there was no evidence for a relationship between food supply (POC flux) and bioturbation intensity, as reflected by 210Pb-DB and 234Th-DB. Bioturbation intensity should be controlled primarily by the composition of the benthic fauna, its specific adaptation to the environmental setting, and the abundance of each species of the benthic community. Food supply can have only an indirect influence on bioturbation intensity. In certain parts of the ocean the a priori overall positive relationship between POC flux and biodiffusivity might include restricted intervals displaying no or even negative relations.

Biogenic silica and silicic acid benthic fluxes of a North-eastern Atlantic Abyssal Locality

Within the framework of the EU-funded BENGAL programme, the effects of seasonality on biogenic silica early diagenesis have been studied at the Porcupine Abyssal Plain (PAP), an abyssal locality located in the northeast Atlantic Ocean. Nine cruises were carried out between August 1996 and August 1998. Silicic acid (DSi) increased downward from 46.2 to 213 µM (mean of 27 profiles). Biogenic silica (BSi) decreased from ca. 2% near the sediment-water interface to <1% at depth. Benthic silicic acid fluxes as measured from benthic chambers were close to those estimated from non-linear DSi porewater gradients. Some 90% of the dissolution occurred within the top 5.5 cm of the sediment column, rather than at the sediment-water interface and the annual DSi efflux was close to 0.057 mol Si/m**2/yr. Biogenic silica accumulation was close to 0.008 mol Si/m**2/yr and the annual opal delivery reconstructed from sedimentary fluxes, assuming steady state, was 0.065 mol Si/m**2/yr. This is in good agreement with the mean annual opal flux determined from sediment trap samples, averaged over the last decade (0.062 mol Si/m**2/yr). Thus ca. 12% of the opal flux delivered to the seafloor get preserved in the sediments. A simple comparison between the sedimentation rate and the dissolution rate in the uppermost 5.5 cm of the sediment column suggests that there should be no accumulation of opal in PAP sediments. However, by combining the BENGAL high sampling frequency with our experimental results on BSi dissolution, we conclude that non-steady state processes associated with the seasonal deposition of fresh biogenic particles may well play a fundamental role in the preservation of BSi in these sediments. This comes about though the way seasonal variability affects the quality of the biogenic matter reaching the seafloor. Hence it influences the intrinsic dissolution properties of the opal at the seafloor and also the part played by non-local mixing events by ensuring the rapid transport of BSi particles deep into the sediment to where saturation is reached.

Mobilities, Entanglements, Transformations. Outline of a Research Project on Pottery Practices in Neolithic Wetland Sites of the Swiss Plateau

A large number of later Neolithic sites (3900–3500BC) in Switzerland, Southern Germany and Eastern France offer outstandingly well preserved archaeological materials from cultural layers. Due to the wide use of dendrochronology, settlement remains and artefact assemblages can now be placed into a precise and fixed chronological framework, thus presenting a unique case within prehistoric archaeology. In earlier research, chronological and regional units were constructed on the basis of pottery. These spacial and temporal units of typical pottery sets were understood as Neolithic cultures, as culturally more or less homogenous entities connected with (ethnic) identities. Today, with a larger data corpus of excavated settlements at hand, we can begin to understand that this period of the past was in fact characterised by a multitude of cultural entanglements and transformations. This is indicated by the occurrence of local and non-local pottery styles in one and the same settlement: for example typically local Cortaillod pottery is found together with NMB-styled pottery in settlements at Lake Neuchâtel or Michelsberg pottery is regularly occurring in settlements at Lake Constance where Pfyn pottery style is the typical local one. These and many more examples show that there must have been complex entanglements of social ties expanding between Eastern France, Southern Germany and the Swiss Plateau. Given these circumstances the former notions of Neolithic culture should be critically revised. Therefore, in late 2014, the Prehistoric Archaeology Department at the Archaeological Institute of University of Berne started a four-year research project funded by Swiss National Science Foundation in late 2014: ‘Mobilities, Entanglements and Transformations in Neolithic Societies of the Swiss Plateau (3900-3500 BC)’. It’s objective is to address the topic sketched above by adopting a mixed methods research (MMR)-design combining qualitative and quantitative approaches from archaeology and archaeometry. The approach is theoretically based on Pierre Bourdieu’s reflexive sociology and his concept of habitus but includes further concepts of practice theories. By shifting the focus to the movement of people, ideas and things – to pottery production practices in contexts of mobility – a deeper understanding of the transformative capacities of encounters can be achieved. This opens the path for new insights of Neolithic societies including social, cultural and economic dynamics that were underestimated in former research.