Particle doses in the pulmonary lobes of electronic and conventional cigarette users

The main aim of the present study was to estimate size segregated doses from e-cigarette aerosols as a function of the airway generation number in lung lobes.. After a 2-second puff, 7.7×1010 particles (DTot) with a surface area of 3.6×103 mm2 (STot), and 3.3×1010 particles with a surface area of 4.2×103 mm2 were deposited in the respiratory system for the electronic and conventional cigarettes, respectively. Alveolar and tracheobronchial deposited doses were compared to the ones received by non-smoking individuals in Western countries, showing a similar order of magnitude. Total regional doses (DR), in head and lobar tracheobronchial and alveolar regions, ranged from 2.7×109 to 1.3×1010 particles and 1.1×109 to 5.3×1010 particles, for the electronic and conventional cigarettes, respectively. DR in the right-upper lung lobe was about twice that found in left-upper lobe and 20% greater in right-lower lobe than the left-lower lobe.

Ethyl-eicosapentaenoic acid in first-episode psychosis : a 1H-MRS study

Ethyl-eicosapentaenoic acid (E-EPA) is an omega-3 fatty acid that has been used in a range of neuropsychiatric conditions with some benefits. However, its mechanism of action is unknown. Here, we investigate its effects on in vivo brain metabolism in first-episode psychosis (FEP). Proton magnetic resonance spectroscopy at 3 T was performed in the temporal lobes of 24 FEP patients before and after 12 weeks of treatment in the context of a larger double-blind, placebo-controlled E-EPA augmentation study. Treatment group effects for glutathione (F1,12=6.1, p=0.03), and a hemisphere-by-group interaction for glutamine/glutamate (F1,20=4.4, p=0.049) were found. Glutathione increased bilaterally and glutamate/glutamine increased in the left hemisphere following E-EPA administration. Improvement in negative symptoms correlated with metabolic brain changes, particularly glutathione (r=-0.57). These results suggest that E-EPA augmentation alters glutathione availability and modulates the glutamine/glutamate cycle in early psychosis, with some of the metabolic brain changes being correlated with negative symptom improvement. Larger confirmatory studies of these postulated metabolic brain effects of E-EPA are warranted.

When and how to treat pulmonary non-tuberculous mycobacterial diseases

Nontuberculous mycobacteria are ubiquitous environmental organisms that have been recognised as a cause of pulmonary infection for over 50 years. Traditionally patients have had underlying risk factors for development of disease; however the proportion of apparently immunocompetent patients involved appears to be rising. Not all patients culture-positive for mycobacteria will have progressive disease, making the diagnosis difficult, though criteria to aid in this process are available. The two main forms of disease are cavitary disease (usually involving the upper lobes) and fibronodular bronchiectasis (predominantly middle and lingular lobes). For patients with disease, combination antibiotic therapy for 12-24 months is generally required for successful treatment, and this may be accompanied by drug intolerances and side effects. Published success rates range from 30-82%. As the progression of disease is variable, for some patients, attention to pulmonary hygiene and underlying diseases without immediate antimycobacterial therapy may be more appropriate. Surgery can be a useful adjunct, though is associated with risks. Randomised controlled trials in well described patients would provide stronger evidence-based data to guide therapy of NTM lung diseases, and thus are much needed.

Myoinositol Abnormalities in Temporal Lobe Epilepsy

Purpose: This study used magnetic resonance spectroscopy (MRS) to examine metabolite abnormalities in the temporal and frontal lobe of patients with temporal lobe epilepsy (TLE) of differing severity. Methods: We investigated myoinositol in TLE by using short-echo MRS in 34 TLE patients [26 late onset (LO-TLE), eight hippocampal sclerosis (HS-TLE)], and 16 controls. Single-voxel short-echo (35 ms) MR spectra of temporal and frontal lobes were acquired at 1.5 T and analyzed by using LCModel. Results: The temporal lobe ipsilateral to seizure origin in HS-TLE, but not LO-TLE, had reduced N-acetylaspartate (NA) and elevated myoinositol (MI; HS-TLE NA, 7.8 ± 1.9 mM, control NA, 9.2 ± 1.3 mM; p < 0.05; HS-TLE MI, 6.1 ± 1.6 mM, control mI 4.9 ± 0.8 mM, p< 0.05). Frontal lobe MI was low in both patient groups (LO-TLE, 4.3 ± 0.8 mM; p < 0.05; HS-TLE, 3.6 ±.05 mM; p < 0.001; controls, 4.8 ± 0.5 mM). Ipsilateral frontal lobes had lower MI (3.8 ± 0.7 mM; p < 0.01) than contralateral frontal lobes (4.3 ± 0.8 mM; p < 0.05). Conclusions: MI changes may distinguish between the seizure focus, where MI is increased, and areas of seizure spread where MI is decreased.

Evidence for carbonate platform failure during rapid sea-level rise; ca 14 000 year old bioclastic flow deposits in the Lesser Antilles

Bioclastic flow deposits offshore from the Soufrie`re Hills volcano on Montserrat in the Lesser Antilles were deposited by the largest volume sediment flows near this active volcano in the last 26 kyr. The volume of these deposits exceeds that of the largest historic volcanic dome collapse in the world, which occurred on Montserrat in 2003. These flows were most probably generated by a large submarine slope failure of the carbonate shelf comprising the south west flank of Antigua or the east flank of Redonda; adjacent islands that are not volcanically active. The bioclastic flow deposits are relatively coarse-grained and either ungraded or poorly graded, and were deposited by non cohesive debris flow and high density turbidity currents. The bioclastic deposit often comprises multiple sub-units that cannot be correlated between core sites; some located just 2 km apart. Multiple sub-units in the bioclastic deposit result from either flow reflection, stacking of multiple debris flow lobes, and/or multi-stage collapse of the initial landslide. This study provides unusually precise constraints on the age of this mass flow event that occurred at ca 14 ka. Few large submarine landslides have been well dated, but the slope failures that have been dated are commonly associated with periods of rapid sea-level change.

Submarine pyroclastic deposits formed at the Soufrière Hills volcano, Montserrat (1995–2003) : what happens when pyroclastic flows enter the ocean?

The Soufrière Hills volcano, Montserrat, West Indies, has undergone a series of dome growth and collapse events since the eruption began in 1995. Over 90% of the pyroclastic material produced has been deposited into the ocean. Sampling of these submarine deposits reveals that the pyroclastic flows mix rapidly and violently with the water as they enter the sea. The coarse components (pebbles to boulders) are deposited proximally from dense basal slurries to form steep-sided, near-linear ridges that intercalate to form a submarine fan. The finer ash-grade components are mixed into the overlying water column to form turbidity currents that flow over distances >30 km from the source. The total volume of pyroclastic material off the east coast of Montserrat exceeds 280 × 106 m3, with 65% deposited in proximal lobes and 35% deposited as distal turbidites.

Cryo-electron tomography of Marburg Virus particles and their morphogenesis within infected cells

Several major human pathogens, including the filoviruses, paramyxoviruses, and rhabdoviruses, package their single-stranded RNA genomes within helical nucleocapsids, which bud through the plasma membrane of the infected cell to release enveloped virions. The virions are often heterogeneous in shape, which makes it difficult to study their structure and assembly mechanisms. We have applied cryo-electron tomography and sub-tomogram averaging methods to derive structures of Marburg virus, a highly pathogenic filovirus, both after release and during assembly within infected cells. The data demonstrate the potential of cryo-electron tomography methods to derive detailed structural information for intermediate steps in biological pathways within intact cells. We describe the location and arrangement of the viral proteins within the virion. We show that the N-terminal domain of the nucleoprotein contains the minimal assembly determinants for a helical nucleocapsid with variable number of proteins per turn. Lobes protruding from alternate interfaces between each nucleoprotein are formed by the C-terminal domain of the nucleoprotein, together with viral proteins VP24 and VP35. Each nucleoprotein packages six RNA bases. The nucleocapsid interacts in an unusual, flexible "Velcro-like" manner with the viral matrix protein VP40. Determination of the structures of assembly intermediates showed that the nucleocapsid has a defined orientation during transport and budding. Together the data show striking architectural homology between the nucleocapsid helix of rhabdoviruses and filoviruses, but unexpected, fundamental differences in the mechanisms by which the nucleocapsids are then assembled together with matrix proteins and initiate membrane envelopment to release infectious virions, suggesting that the viruses have evolved different solutions to these conserved assembly steps.

Emplacement of pyroclastic deposits offshore Montserrat : insights from 3D seismic data

During the current (1995-present) eruptive phase of the Soufrière Hills volcano on Montserrat, voluminous pyroclastic flows entered the sea off the eastern flank of the island, resulting in the deposition of well-defined submarine pyroclastic lobes. Previously reported bathymetric surveys documented the sequential construction of these deposits, but could not image their internal structure, the morphology or extent of their base, or interaction with the underlying sediments. We show, by combining these bathymetric data with new high-resolution three dimensional (3D) seismic data, that the sequence of previously detected pyroclastic deposits from different phases of the ongoing eruptive activity is still well preserved. A detailed interpretation of the 3D seismic data reveals the absence of significant (> 3. m) basal erosion in the distal extent of submarine pyroclastic deposits. We also identify a previously unrecognized seismic unit directly beneath the stack of recent lobes. We propose three hypotheses for the origin of this seismic unit, but prefer an interpretation that the deposit is the result of the subaerial flank collapse that formed the English's Crater scarp on the Soufrière Hills volcano. The 1995-recent volcanic activity on Montserrat accounts for a significant portion of the sediments on the southeast slope of Montserrat, in places forming deposits that are more than 60. m thick, which implies that the potential for pyroclastic flows to build volcanic island edifices is significant.

Anterior temporal cortex and semantic memory : reconciling findings from neuropsychology and functional imaging

Studies of semantic impairment arising from brain disease suggest that the anterior temporal lobes are critical for semantic abilities in humans; yet activation of these regions is rarely reported in functional imaging studies of healthy controls performing semantic tasks. Here, we combined neuropsychological and PET functional imaging data to show that when healthy subjects identify concepts at a specific level, the regions activated correspond to the site of maximal atrophy in patients with relatively pure semantic impairment. The stimuli were color photographs of common animals or vehicles, and the task was category verification at specific (e.g., robin), intermediate (e.g., bird), or general (e.g., animal) levels. Specific, relative to general, categorization activated the antero-lateral temporal cortices bilaterally, despite matching of these experimental conditions for difficulty. Critically, in patients with atrophy in precisely these areas, the most pronounced deficit was in the retrieval of specific semantic information.

Gray matter deficits, mismatch negativity, and outcomes in schizophrenia

Reduced mismatch negativity (MMN) in response to auditory change is a well-established finding in schizophrenia and has been shown to be correlated with impaired daily functioning, rather than with hallmark signs and symptoms of the disorder. In this study, we investigated (1) whether the relationship between reduced MMN and impaired daily functioning is mediated by cortical volume loss in temporal and frontal brain regions in schizophrenia and (2) whether this relationship varies with the type of auditory deviant generating MMN. MMN in response to duration, frequency, and intensity deviants was recorded from 18 schizophrenia subjects and 18 pairwise age- and gender-matched healthy subjects. Patients’ levels of global functioning were rated on the Social and Occupational Functioning Assessment Scale. High-resolution structural magnetic resonance scans were acquired to generate average cerebral cortex and temporal lobe models using cortical pattern matching. This technique allows accurate statistical comparison and averaging of cortical measures across subjects, despite wide variations in gyral patterns. MMN amplitude was reduced in schizophrenia patients and correlated with their impaired day-to-day function level. Only in patients, bilateral gray matter reduction in Heschl’s gyrus, as well as motor and executive regions of the frontal cortex, correlated with reduced MMN amplitude in response to frequency deviants, while reduced gray matter in right Heschl’s gyrus also correlated with reduced MMN to duration deviants. Our findings further support the importance of MMN reduction in schizophrenia by linking frontotemporal cerebral gray matter pathology to an automatically generated event-related potential index of daily functioning.

Functional neuroanatomy of auditory mismatch processing : an event-related fMRI study of duration-deviant oddballs

This study was designed to identify the neural networks underlying automatic auditory deviance detection in 10 healthy subjects using functional magnetic resonance imaging. We measured blood oxygenation level-dependent contrasts derived from the comparison of blocks of stimuli presented as a series of standard tones (50 ms duration) alone versus blocks that contained rare duration-deviant tones (100 ms) that were interspersed among a series of frequent standard tones while subjects were watching a silent movie. Possible effects of scanner noise were assessed by a “no tone” condition. In line with previous positron emission tomography and EEG source modeling studies, we found temporal lobe and prefrontal cortical activation that was associated with auditory duration mismatch processing. Data were also analyzed employing an event-related hemodynamic response model, which confirmed activation in response to duration-deviant tones bilaterally in the superior temporal gyrus and prefrontally in the right inferior and middle frontal gyri. In line with previous electrophysiological reports, mismatch activation of these brain regions was significantly correlated with age. These findings suggest a close relationship of the event-related hemodynamic response pattern with the corresponding electrophysiological activity underlying the event-related “mismatch negativity” potential, a putative measure of auditory sensory memory.

Petrology and textural classification of the Jericho kimberlite, northern Slave Province, Nunavut, Canada

The paper presents data on petrology, bulk rock and mineral compositions, and textural classification of the Middle Jurassic Jericho kimberlite (Slave craton, Canada). The kimberlite was emplaced as three steep-sided pipes in granite that was overlain by limestones and minor soft sediments. The pipes are infilled with hypabyssal and pyroclastic kimberlites and connected to a satellite pipe by a dyke. The Jericho kimberlite is classified as a Group Ia, lacking groundmass tetraferriphlogopite and containing monticellite pseudomorphs. The kimberlite formed, during several consecutive emplacement events of compositionally different batches of kimberlite magma. Core-logging and thin-section observations identified at least two phases of hypabyssal kimberlites and three phases of pyroclastic kimberlites. Hypabyssal kimberlites intruded as a main dyke (HK1) and as late small-volume aphanitic and vesicular dykes. Massive pyroclastic kimberlite (MPK1) predominantly filled the northern and southern lobes of the pipe and formed from magma different from the HK1 magma. The MPK1 magma crystallized Ti-, Fe-, and Cr-rich phlogopite without rims of barian phlogopite, and clinopyroxene and spinel without atoll structures. MPK1 textures, superficially reminiscent of tuffisitic kimberlite, are caused by pervasive contamination by granite xenoliths. The next explosive events filled the central lobe with two varieties of pyroclastic kimberlite: (1) massive and (2) weakly bedded, normally graded pyroclastic kimberlite. The geology of the Jericho pipe differs from the geology of South African or the Prairie kimberlites, but may resemble Lac de Gras pipes, in which deeper erosion removed upper fades of resedimented kimberlites.

Mapping the regional influence of genetics on brain structure variability - A Tensor-Based Morphometry study

Genetic and environmental factors influence brain structure and function profoundly. The search for heritable anatomical features and their influencing genes would be accelerated with detailed 3D maps showing the degree to which brain morphometry is genetically determined. As part of an MRI study that will scan 1150 twins, we applied Tensor-Based Morphometry to compute morphometric differences in 23 pairs of identical twins and 23 pairs of same-sex fraternal twins (mean age: 23.8 ± 1.8 SD years). All 92 twins' 3D brain MRI scans were nonlinearly registered to a common space using a Riemannian fluid-based warping approach to compute volumetric differences across subjects. A multi-template method was used to improve volume quantification. Vector fields driving each subject's anatomy onto the common template were analyzed to create maps of local volumetric excesses and deficits relative to the standard template. Using a new structural equation modeling method, we computed the voxelwise proportion of variance in volumes attributable to additive (A) or dominant (D) genetic factors versus shared environmental (C) or unique environmental factors (E). The method was also applied to various anatomical regions of interest (ROIs). As hypothesized, the overall volumes of the brain, basal ganglia, thalamus, and each lobe were under strong genetic control; local white matter volumes were mostly controlled by common environment. After adjusting for individual differences in overall brain scale, genetic influences were still relatively high in the corpus callosum and in early-maturing brain regions such as the occipital lobes, while environmental influences were greater in frontal brain regions that have a more protracted maturational time-course.

Genetics of brain fiber architecture and intellectual performance

The study is the first to analyze genetic and environmental factors that affect brain fiber architecture and its genetic linkage with cognitive function. We assessed white matter integrity voxelwise using diffusion tensor imaging at high magnetic field (4 Tesla), in 92 identical and fraternal twins. White matter integrity, quantified using fractional anisotropy (FA), was used to fit structural equation models (SEM) at each point in the brain, generating three-dimensional maps of heritability. We visualized the anatomical profile of correlations between white matter integrity and full-scale, verbal, and performance intelligence quotients (FIQ, VIQ, and PIQ). White matter integrity (FA) was under strong genetic control and was highly heritable in bilateral frontal (a 2 = 0.55, p = 0.04, left; a 2 = 0.74, p = 0.006, right), bilateral parietal (a 2 = 0.85, p < 0.001, left; a 2 = 0.84, p < 0.001, right), and left occipital (a 2 = 0.76, p = 0.003) lobes, and was correlated with FIQ and PIQ in the cingulum, optic radiations, superior fronto- occipital fasciculus, internal capsule, callosal isthmus, and the corona radiata (p = 0.04 for FIQ and p = 0.01 for PIQ, corrected for multiple comparisons). In a cross-trait mapping approach, common genetic factors mediated the correlation between IQ and white matter integrity, suggesting a common physiological mechanism for both, and common genetic determination. These genetic brain maps reveal heritable aspects of white matter integrity and should expedite the discovery of single-nucleotide polymorphisms affecting fiber connectivity and cognition.

The structure and connectivity of semantic memory in the healthy older adult brain

The anterior temporal lobes (ATLs) have been proposed to serve as a "hub" linking amodal or domain general information about the meaning of words, objects, facts and people distributed throughout the brain in semantic memory. The two primary sources of evidence supporting this proposal, viz. structural imaging studies in semantic dementia (SD) patients and functional imaging investigations, are not without problems. Similarly, knowledge about the anatomo-functional connectivity of semantic memory is limited to a handful of intra-operative electrocortical stimulation (IES) investigations in patients. Here, using principal components analyses (PCA) of a battery of conceptual and non-conceptual tests coupled with voxel based morphometry (VBM) and diffusion tensor imaging (DTI) in a sample of healthy older adults aged 55-85. years, we show that amodal semantic memory relies on a predominantly left lateralised network of grey matter regions involving the ATL, posterior temporal and posterior inferior parietal lobes, with prominent involvement of the left inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus fibre pathways. These results demonstrate relationships between semantic memory, brain structure and connectivity essential for human communication and cognition.