Combined EEG-fMRI and tractography to visualise propagation of epileptic activity

In a patient with refractory temporal lobe epilepsy, EEG-fMRI showed activation in association with left anterior temporal interictal discharges, in the left temporal, parietal and occipital lobes. Dynamic causal modelling suggested propagation of neural activity from the temporal focus to the area of occipital activation. Tractography showed connections from the site of temporal lobe activation to the site of occipital activation. This demonstrates the principle of combining EEG-fMRI and tractography to delineate the pathways of propagation of epileptic activity

Endemic and cosmopolitan fungal taxa exhibit differential abundances in total and active communities of Antarctic soils

Our understanding of the diversity and community dynamics of soil fungi has increased greatly through the use of DNA‐based identification. Community characterisation of metabolically active communities via RNA sequencing has previously revealed differences between ‘active’ and ‘total’ fungal communities, which may be influenced by the persistence of DNA from non‐active components. However, it is not known how fungal traits influence their prevalence in these contrasting community profiles. In this study, we co‐extracted DNA and RNA from soil collected from three Antarctic islands to test for differences between total and active soil fungal communities. By matching these geographically isolated fungi against a global dataset of soil fungi, we show that widely dispersed taxa are often more abundant in the total community, whilst taxa restricted to Antarctica are more likely to have higher abundance in the active community. In addition, we find that active communities have lower richness, and show a reduction in the abundance of the most dominant fungi, whilst there are consistent differences in the abundances of certain taxonomic groups between the total and active communities. These results suggest that the views of soil fungal communities offered by DNA‐ and RNA‐based characterisation differ in predictable ways

Akimiski Island, Nunavut, Canada: The Use of Cree Oral History and Sea-Level Retrodiction to Resolve Aboriginal Title

On 1 April 1999, Akimiski Island of the western James Bay region of northern Ontario, Canada, was included in the newly formed territory of Nunavut, Canada—an Inuit-dominated territory—even though the Inuit had never asserted Aboriginal title to the island. By contrast, the Omushkegowuk Cree of the western James Bay region have asserted Aboriginal title to Akimiski Island. The Government of Canada by their action (or inaction) has reversed the onus of responsibility for proof of Aboriginal title from the Inuit to the Cree. In other words, the Government of Canada did not follow their own guidelines and the common-law test for proof of Aboriginal title. In this paper, we documented and employed Cree oral history as well as a sea-level retrodiction (based on state-of-the-art numerical modeling of past sea-level changes in James Bay), which incorporated a modified ICE-6G ice history and a 3-D model of Earth structure, to establish that criterion 2 of the test for Aboriginal title has now been fully met. In other words, Cree traditional use and occupancy of Akimiski Island was considered sufficiently factual at the time of assertion of sovereignty by European nations. As all the criteria of the common-law test for proof of Aboriginal title in Canada, with respect to Akimiski Island, have now been addressed, the Cree have sufficient basis to initiate the process of a formal land claim.Le 1er avril 1999, l’île Akimiski, située dans la région ouest de la baie James, dans le nord de l’Ontario, au Canada, a été intégrée au nouveau territoire du Nunavut, territoire dominé par les Inuits, même si ceux-ci n’avaient jamais revendiqué le titre ancestral de cette île. En revanche, les Cris omushkegowuk de la région ouest de la baie James ont revendiqué leur titre ancestral à l’égard de l’île Akimiski. Le geste (ou l’absence de geste) du gouvernement du Canada a eu pour effet d’inverser la responsabilité de prouver le titre ancestral des Inuits aux Cris. Autrement dit, le gouvernement du Canada n’a pas respecté ses propres directives et les critères de droit commun comme preuve de titre ancestral. Dans cet article, nous avons documenté et employé l’histoire orale crie ainsi qu’une rétrodiction du niveau de la mer (d’après une modélisation numérique perfectionnée d’anciens changements du niveau de la mer de la baie James), contenant un historique modifié de la glace ICE-6G et une modélisation en trois dimensions de la structure de la Terre, afin d’établir que le critère 2 des critères du titre ancestral est maintenant entièrement atteint. Autrement dit, l’usage et l’occupation traditionnels de l’île Akimiski par les Cris ont été considérés comme des faits suffisants au moment de la revendication de la souveraineté par les nations européennes. Puisque tous les critères de droit commun permettant de prouver le titre ancestral de l’île Akimiski au Canada ont maintenant été respectés, les Cris disposent de fondements suffisants pour entreprendre une revendication territoriale officielle

A P53-Independent DNA Damage Response Suppresses Oncogenic Proliferation and Genome Instability

The Mre11-Rad50-Nbs1 complex is a DNA double-strand break sensor that mediates a tumor-suppressive DNA damage response (DDR) in cells undergoing oncogenic stress, yet the mechanisms underlying this effect are poorly understood. Using a genetically inducible primary mammary epithelial cell model, we demonstrate that Mre11 suppresses proliferation and DNA damage induced by diverse oncogenic drivers through a p53-independent mechanism. Breast tumorigenesis models engineered to express a hypomorphic Mre11 allele exhibit increased levels of oncogene-induced DNA damage, R-loop accumulation, and chromosomal instability with a characteristic copy number loss phenotype. Mre11 complex dysfunction is identified in a subset of human triple-negative breast cancers and is associated with increased sensitivity to DNA-damaging therapy and inhibitors of ataxia telangiectasia and Rad3 related (ATR) and poly (ADP-ribose) polymerase (PARP). Thus, deficiencies in the Mre11-dependent DDR drive proliferation and genome instability patterns in p53-deficient breast cancers and represent an opportunity for therapeutic exploitation

"Ordinary, the same as anywhere else": notes on the management of spoiled identity in 'marginal' middle class neighbourhoods

Urban sociologists are becoming increasingly interested in neighbourhood as a source of middle-class identity. Particular emphasis is currently being given to two types of middle-class neighbourhood; gentrified urban neighbourhoods of ‘distinction’ and inconspicuous ‘suburban landscapes of privilege’. However, there has been a dearth of work on ‘marginal’ middle-class neighbourhoods that are similarly ‘inconspicuous’ rather than distinctive, but less exclusive, thus containing sources of ‘spoiled identity’. This article draws on data gathered from two ‘marginal’ middleclass neighbourhoods that contained a particular source of ‘spoiled identity’: social renters. Urban sociological analyses of neighbour responses to these situations highlight a process of dis-identification with the maligned object, which exacerbates neighbour differences. Our analysis of data from the ‘marginal’ middle-class neighbourhoods suggests something entirely different and Goffmanesque. This entailed the management of spoiled identity, which emphasized similarities rather than differences between neighbours.</p

Simulation techniques for cosmological simulations

Modern cosmological observations allow us to study in great detail the evolution and history of the large scale structure hierarchy. The fundamental problem of accurate constraints on the cosmological parameters, within a given cosmological model, requires precise modelling of the observed structure. In this paper we briefly review the current most effective techniques of large scale structure simulations, emphasising both their advantages and shortcomings. Starting with basics of the direct N-body simulations appropriate to modelling cold dark matter evolution, we then discuss the direct-sum technique GRAPE, particle-mesh (PM) and hybrid methods, combining the PM and the tree algorithms. Simulations of baryonic matter in the Universe often use hydrodynamic codes based on both particle methods that discretise mass, and grid-based methods. We briefly describe Eulerian grid methods, and also some variants of Lagrangian smoothed particle hydrodynamics (SPH) methods.Comment: 42 pages, 16 figures, accepted for publication in Space Science Reviews, special issue "Clusters of galaxies: beyond the thermal view", Editor J.S. Kaastra, Chapter 12; work done by an international team at the International Space Science Institute (ISSI), Bern, organised by J.S. Kaastra, A.M. Bykov, S. Schindler & J.A.M. Bleeke

Testing and extending strategies for identifying genetic disease–related encounters in pediatric patients

Purpose: To better understand health care utilization and develop decision support tools, methods for identifying patients with suspected genetic diseases (GDs) are needed. Previous studies had identified inpatient-relevant International Classification of Diseases (ICD) codes that were possibly, probably, or definitely indicative of GDs. We assessed whether these codes identified GD-related inpatient, outpatient, and emergency department encounters among pediatric patients with suspected GDs from a previous study (the North Carolina Clinical Genomic Evaluation by Next-Generation Exome Sequencing [NCGENES] study). Methods: Using the electronic medical records of 140 pediatric patients from the NCGENES study, we characterized the presence of ICD codes representing possible, probable, or definite GD-related diagnoses across encounter types. In addition, we examined codes from encounters for which initially no GD-related codes had been found and determined whether these codes were indicative of a GD. Results: Among NCGENES patients with visits between 2014 and 2017, 92% of inpatient, 75% of emergency department, and 63% of outpatient encounters included ≥1 GD-related code. Encounters with highly specific (ie, definite) GD codes had fewer low-specificity GD codes than encounters with only low-specificity GD codes. We identified an additional 32 ICD-9 and 56 ICD-10 codes possibly indicative of a GD. Conclusion: Code-based strategies can be refined to assess health care utilization among pediatric patients and may contribute to a systematic approach to identify patients with suspected GDs

High School Exit Examinations: When Do Learning Effects Generalize?

This paper reviews international and domestic evidence on the effects of three types of high school exit exam systems: voluntary curriculum-based external exit exams, universal curriculum-based external exit exam systems and minimum competency tests that must be passed to receive a regular high school diploma. The nations and provinces that use Universal CBEEES (and typically teacher grades as well) to signal student achievement have significantly higher achievement levels and smaller differentials by family background than otherwise comparable jurisdictions that base high stakes decisions on voluntary college admissions tests and/or teacher grades. The introduction of Universal CBEEES in New York and North Carolina during the 1990s was associated with large increases in math achievement on NAEP tests. Research on MCTs and high school accountability tests is less conclusive because these systems are new and have only been implemented in one country. Cross-section studies using a comprehensive set of controls for family background have not found that students in MCT states score higher on audit tests like the NAEP that carry no stakes for the test taker. The analysis reported in table 1 tells us that the five states that introduced MCTs during the 1990s had significantly larger improvements on NAEP tests than states that made no change in their student accountability regime. The gains, however, are smaller than for the states introducing Universal CBEEES. New York and North Carolina. The most positive finding about MCTs is that students in MCT states earn significantly more during the first eight years after graduation than comparable students in other states suggesting that MCTs improve employer perceptions of the quality of the recent graduates of local high schools

Influence of coding variability in APP-Aß metabolism genes in sporadic Alzheimer's disease

The cerebral deposition of Aß42, a neurotoxic proteolitic derivate of amyloid precursor protein (APP), is a central event in Alzheimer’s disease (AD)(Amyloid hypothesis). Given the key role of APP-Aß metabolism in AD pathogenesis, we selected 29 genes involved in APP processing, Aß degradation and clearance. We then used exome and genome sequencing to investigate the single independent (single-variant association test) and cumulative (gene-based association test) effect of coding variants in these genes as potential susceptibility factors for AD, in a cohort composed of 435 sporadic and mainly late-onset AD cases and 801 elderly controls from North America and the UK. Our study shows that common coding variability in these genes does not play a major role for the disease development. In the single-variant association analysis, the main hits, which were nominally significant, were found to be very rare coding variants (MAF 0.3%-0.8%) that map to genes involved in APP processing (MEP1B), trafficking and recycling (SORL1), Aß extracellular degradation (ACE) and clearance (LRP1). Moreover, four genes (ECE1, LYZ, TTR and MME) have been found as nominally associated to AD using c-alpha and SKAT tests. We suggest that Aβ degradation and clearance, rather than Aβ production, may play a crucial role in the etiology of sporadic AD