EEG–fMRI of idiopathic and secondarily generalized epilepsies

We used simultaneous EEG and functional MRI (EEG–fMRI) to study generalized spike wave activity (GSW) in idiopathic and secondary generalized epilepsy (SGE). Recent studies have demonstrated thalamic and cortical fMRI signal changes in association with GSW in idiopathic generalized epilepsy (IGE). We report on a large cohort of patients that included both IGE and SGE, and give a functional interpretation of our findings. Forty-six patients with GSW were studied with EEG–fMRI; 30 with IGE and 16 with SGE. GSW-related BOLD signal changes were seen in 25 of 36 individual patients who had GSW during EEG–fMRI. This was seen in thalamus (60%) and symmetrically in frontal cortex (92%), parietal cortex (76%), and posterior cingulate cortex/precuneus (80%). Thalamic BOLD changes were predominantly positive and cortical changes predominantly negative. Group analysis showed a negative BOLD response in the cortex in the IGE group and to a lesser extent a positive response in thalamus. Thalamic activation was consistent with its known role in GSW, and its detection in individual cases with EEG–fMRI may in part be related to the number and duration of GSW epochs recorded. The spatial distribution of the cortical fMRI response to GSW in both IGE and SGE involved areas of association cortex that are most active during conscious rest. Reduction of activity in these regions during GSW is consistent with the clinical manifestation of absence seizures

Location! Location! Location!: Reference Service in Non-Library Settings

The decline in the number of face-to-face reference transactions has implications that are of concern to librarians, as well as the faculty and students we serve. A strategy to address this is to take reference to locations that are “more convenient” for users – locations where they already work, study and gather. Three reference librarians shared their experiences with offering services in non-library settings, such as a faculty office building, a computer lab in a classroom, a student lounge, and a departmental library room. The objectives and experiences of these librarians vary, as do their specialized subject disciplines. This presentation detailed the spaces, scheduling, advertising, faculty/student relationships, evaluation/assessment strategy, and future plans unique to each locale. Handouts included a checklist of considerations for those planning mobile reference service, and a list of benefits and disadvantages from offering these services

The tail of the Jurassic fish Leedsichthys problematicus (Osteichthyes: Actinopterygii) collected by Alfred Nicholson Leeds - an example of the importance of historical records in palaeontology

The specimen of the tail of <i>Leedsichthys problematicus</i>, now in The Natural History Museum, London, was one of the most spectacular fossil vertebrates from the Oxford Clay Formation of Peterborough, but as an isolated find it shares no bones in common with the holotype of the genus and species. However, a letter from Alfred Nicholson Leeds and related documents cast valuable new light on the excavation of the tail, indicating that it was discovered with cranial bones, gill-rakers, and two pectoral fins, thereby including elements that can potentially be compared with those of the holotype. The documents also clearly indicate that The Natural History Museum's specimen is not part of the same individual as any other numbered specimen of <i>Leedsichthys</i> as had been speculated on other occasions. The maximum size of the animal represented by The Natural History Museum's specimen was possibly around 9 metres, considerably less than previous estimates of up to 27.6 metres for <i>Leedsichthys</i>. Historical documentary evidence should therefore be rigorously checked both when studying historical specimens in science, and in preparing text for museum display labels

Models and image: reconstruction in electrical impedance tomography of human brain function

Electrical Impedance Tomography (EIT) of brain function has the potential to provide a rapid portable bedside neuroimaging device. Recently, our group published the first ever EIT images of evoked activity recorded with scalp electrodes. While the raw data showed encouraging, reproducible changes of a few per cent, the images were noisy. The poor image quality was due, in part, to the use of a simplified reconstruction algorithm which modelled the head as a homogeneous sphere. The purpose of this work has been to develop new algorithms in which the model incorporates extracerebral layers and realistic geometry, and to assess their effect on image quality. An algorithm was suggested which allowed fair comparison between reconstructions assuming analytical and numerical (Finite Element Method - FEM) models of the head as a homogeneous sphere and as concentric spheres representing the brain, CSF, skull and scalp. Comparison was also made between these and numerical models of the head as a homogeneous, head-shaped volume and as a head-shaped volume with internal compartments of contrasting resistivity. The models were tested on computer simulations, on spherical and head-shaped, saline-filled tanks and on data collected during human evoked response studies. EIT also has the potential to image resistance changes which occur during neuronal depolarization in the cortex and last tens of milliseconds. Also presented in this thesis is an estimate of their magnitude made using a mathematical model, based on cable theory, of resistance changes at DC during depolarization in the cerebral cortex. Published values were used for the electrical properties and geometry of cell processes (Rail, 1975). The study was performed in order to estimate the resultant scalp signal that might be obtained and to assess the ability of EIT to produce images of neuronal depolarization

Finding a (Pine) Needle in a Haystack: Chloroplast Genome Sequence Divergence in Rare and Widespread Pines

Critical to conservation efforts and other investigations at low taxonomic levels, DNA sequence data offer important insights into the distinctiveness, biogeographic partitioning and evolutionary histories of species. The resolving power of DNA sequences is often limited by insufficient variability at the intraspecific level. This is particularly true of studies involving plant organelles, as the conservative mutation rate of chloroplasts and mitochondria makes it difficult to detect polymorphisms necessary to track genealogical relationships among individuals, populations and closely related taxa, through space and time. Massively parallel sequencing (MPS) makes it possible to acquire entire organelle genome sequences to identify cryptic variation that would be difficult to detect otherwise. We are using MPS to evaluate intraspecific chloroplast-level divergence across biogeographic boundaries in narrowly endemic and widespread species of Pinus. We focus on one of the world\u27s rarest pines - Torrey pine (Pinus torreyana) - due to its conservation interest and because it provides a marked contrast to more widespread pine species. Detailed analysis of nearly 90% ( approximately 105 000 bp each) of these chloroplast genomes shows that mainland and island populations of Torrey pine differ at five sites in their plastome, with the differences fixed between populations. This is an exceptionally low level of divergence (1 polymorphism/ approximately 21 kb), yet it is comparable to intraspecific divergence present in widespread pine species and species complexes. Population-level organelle genome sequencing offers new vistas into the timing and magnitude of divergence within species, and is certain to provide greater insight into pollen dispersal, migration patterns and evolutionary dynamics in plants

The interaction of lean and building information modeling in construction

Lean construction and Building Information Modeling are quite different initiatives, but both are having profound impacts on the construction industry. A rigorous analysis of the myriad specific interactions between them indicates that a synergy exists which, if properly understood in theoretical terms, can be exploited to improve construction processes beyond the degree to which it might be improved by application of either of these paradigms independently. Using a matrix that juxtaposes BIM functionalities with prescriptive lean construction principles, fifty-six interactions have been identified, all but four of which represent constructive interaction. Although evidence for the majority of these has been found, the matrix is not considered complete, but rather a framework for research to explore the degree of validity of the interactions. Construction executives, managers, designers and developers of IT systems for construction can also benefit from the framework as an aid to recognizing the potential synergies when planning their lean and BIM adoption strategies

Self-Affirmation Improves Problem-Solving under Stress

High levels of acute and chronic stress are known to impair problem-solving and creativity on a broad range of tasks. Despite this evidence, we know little about protective factors for mitigating the deleterious effects of stress on problem-solving. Building on previous research showing that self-affirmation can buffer stress, we tested whether an experimental manipulation of self-affirmation improves problem-solving performance in chronically stressed participants. Eighty undergraduates indicated their perceived chronic stress over the previous month and were randomly assigned to either a self-affirmation or control condition. They then completed 30 difficult remote associate problem-solving items under time pressure in front of an evaluator. Results showed that self-affirmation improved problem-solving performance in underperforming chronically stressed individuals. This research suggests a novel means for boosting problem-solving under stress and may have important implications for understanding how self-affirmation boosts academic achievement in school settings. © 2013 Creswell et al

GABA-modulating bacteria of the human gut microbiota.

The gut microbiota affects many important host functions, including the immune response and the nervous system1. However, while substantial progress has been made in growing diverse microorganisms of the microbiota2, 23-65% of species residing in the human gut remain uncultured3,4, which is an obstacle for understanding their biological roles. A likely reason for this unculturability is the absence in artificial media of key growth factors that are provided by neighbouring bacteria in situ5,6. In the present study, we used co-culture to isolate KLE1738, which required the presence of Bacteroides fragilis to grow. Bioassay-driven purification of B. fragilis supernatant led to the isolation of the growth factor, which, surprisingly, is the major inhibitory neurotransmitter GABA (γ-aminobutyric acid). GABA was the only tested nutrient that supported the growth of KLE1738, and a genome analysis supported a GABA-dependent metabolism mechanism. Using growth of KLE1738 as an indicator, we isolated a variety of GABA-producing bacteria, and found that Bacteroides ssp. produced large quantities of GABA. Genome-based metabolic modelling of the human gut microbiota revealed multiple genera with the predicted capability to produce or consume GABA. A transcriptome analysis of human stool samples from healthy individuals showed that GABA-producing pathways are actively expressed by Bacteroides, Parabacteroides and Escherichia species. By coupling 16S ribosmal RNA sequencing with functional magentic resonance imaging in patients with major depressive disorder, a disease associated with an altered GABA-mediated response, we found that the relative abundance levels of faecal Bacteroides are negatively correlated with brain signatures associated with depression

Non-invasive assessment of murine PD-L1 levels in syngeneic tumor models by nuclear imaging with nanobody tracers

Blockade of the inhibitory PD-1/PD-L1 immune checkpoint axis is a promising cancer treatment. Nonetheless, a significant number of patients and malignancies do not respond to this therapy. To develop a screen for response to PD-1/PD-L1 inhibition, it is critical to develop a non-invasive tool to accurately assess dynamic immune checkpoint expression. Here we evaluated non-invasive SPECT/CT imaging of PD-L1 expression, in murine tumor models with varying PD-L1 expression, using high affinity PD-L1-specific nanobodies (Nbs). We generated and characterized 37 Nbs recognizing mouse PD-L1. Among those, four Nbs C3, C7, E2 and E4 were selected and evaluated for preclinical imaging of PD-L1 in syngeneic mice. We performed SPECT/CT imaging in wild type versus PD-L1 knock-out mice, using Technetium-99m (99mTc) labeled Nbs. Nb C3 and E2 showed specific antigen binding and beneficial biodistribution. Through the use of CRISPR/Cas9 PD-L1 knock-out TC-1 lung epithelial cell lines, we demonstrate that SPECT/CT imaging using Nb C3 and E2 identifies PD-L1 expressing tumors, but not PD-L1 non-expressing tumors, thereby confirming the diagnostic potential of the selected Nbs. In conclusion, these data show that Nbs C3 and E2 can be used to non-invasively image PD-L1 levels in the tumor, with the strength of the signal correlating with PD-L1 levels. These findings warrant further research into the use of Nbs as a tool to image inhibitory signals in the tumor environment

Is there evidence for export-led adoption of ISO 14001? A review of the literature using meta-regression

Does the export orientation of a firm affect the likelihood that it adopts an environmental management certification? We use meta-regression methods to analyze systematically the corpus of published research on export-led adoption of the largest and most prominent certification, ISO 14001. We show that the explanatory variables authors choose to include in their models reflect the tenets of stakeholder and institutional theories. We also find that the literature suffers from substantial publication bias but that, once this is accounted for appropriately, a genuine effect remains. The evidence from 20 years of published studies taken as a whole is that export does incentivize the adoption of the standard as often hypothesized by proponents of voluntary approaches and self-regulation