Clustering of tau-immunoreactive pathology in chronic traumatic encephalopathy

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder which may result from repetitive brain injury. A variety of tau-immunoreactive pathologies are present, including neurofibrillary tangles (NFT), neuropil threads (NT), dot-like grains (DLG), astrocytic tangles (AT), and occasional neuritic plaques (NP). In tauopathies, cellular inclusions in the cortex are clustered within specific laminae, the clusters being regularly distributed parallel to the pia mater. To determine whether a similar spatial pattern is present in CTE, clustering of the tau-immunoreactive pathology was studied in the cortex, hippocampus, and dentate gyrus in 11 cases of CTE and 7 cases of Alzheimer’s disease neuropathologic change (ADNC) without CTE. In CTE: (1) all aspects of tau-immunoreactive pathology were clustered and the clusters were frequently regularly distributed parallel to the tissue boundary, (2) clustering was similar in two CTE cases with minimal co-pathology compared with cases with associated ADNC or TDP-43 proteinopathy, (3) in a proportion of cortical gyri, estimated cluster size was similar to that of cell columns of the cortico-cortical pathways, and (4) clusters of the tau-immunoreactive pathology were infrequently spatially correlated with blood vessels. The NFT and NP in ADNC without CTE were less frequently randomly or uniformly distributed and more frequently in defined clusters than in CTE. Hence, the spatial pattern of the tau-immunoreactive pathology observed in CTE is typical of the tauopathies but with some distinct differences compared to ADNC alone. The spread of pathogenic tau along anatomical pathways could be a factor in the pathogenesis of the disease

An Estimation of the Entomological Inoculation Rate for Ifakara: A Semi-Urban Area in a Region of Intense Malaria Transmission in Tanzania.

An entomological study on vectors of malaria and their relative contribution to Plasmodium falciparum transmission in the semi-urban area of Ifakara, south-eastern Tanzania, was conducted. A total of 32 houses were randomly sampled from the area and light trap catches (LTC) performed in one room in each house every 2 weeks for 1 year. A total of 147 448 mosquitoes were caught from 789 LTC; 26 134 Anopheles gambiae s.l., 615 A. funestus, 718 other anophelines and 119 981 culicines. More than 60% of the total A. gambiae s.l. were found in five (0.6%) LTCs, with a maximum of 5889 caught in a single trap. Of 505 A. gambiae s.l. speciated by polymerase chain reaction, 91.5% were found to be A. arabiensis. Plasmodium falciparum sporozoite enzyme-linked immunosorbent assay tests were performed on 10 108 anopheles mosquitoes and 39 (0.38%) were positive. Entomological inoculation rate (EIR) estimates were generated using a standard method and an alternative method that allows the calculation of confidence intervals based on a negative binomial distribution of sporozoite positive mosquitoes. Overall EIR estimates were similar; 31 vs. 29 [95% confidence interval (CI): 19, 44] infectious bites per annum, respectively. The EIR ranged from 4 (95% CI: 1, 17) in the cool season to 108 (95% CI: 69, 170) in the wet season and from 54 (95% CI: 30, 97) in the east of the town to 15 (95% CI: 8, 30) in the town centre. These estimates show large variations over short distances in time and space. They are all markedly lower than those reported from nearby rural areas and for other parts of Tanzania

Myocardial infarction, ST-elevation and non-ST-elevation myocardial infarction and modelled daily pollution concentrations; a case-crossover analysis of MINAP data

Objectives: To investigate associations between daily concentrations of air pollution and myocardial infarction (MI), ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI). Methods: Modelled daily ground-level gaseous, total and speciated particulate pollutant concentrations and ground-level daily mean temperature, all at 5 km x 5 km horizontal resolution, were linked to 202,550 STEMI and 322,198 NSTEMI events recorded on the England and Wales Myocardial Ischaemia National Audit Project (MINAP) database. The study period was 2003-2010. A case-crossover design was used, stratified by year, month, and day of the week. Data were analysed using conditional logistic regression, with pollutants modelled as unconstrained distributed lags 0-2 days. Results are presented as percentage change in risk per 10 µg/m3 increase in the pollutant relevant metric, having adjusted for daily mean temperature, public holidays, weekly flu consultation rates, and a sine-cosine annual cycle. Results: There was no evidence of an association between MI or STEMI and any of O3, NO2, PM2.5, PM10 or selected PM2.5 components (sulphate and elemental carbon). For NSTEMI there was a positive association with daily maximum 1-hour NO2 (0.27% (95% CI: 0.01 to 0.54)), which persisted following adjustment for O3 and adjustment for PM2.5. The association appeared to be confined to the midland and southern regions of England and Wales. Conclusions: The study found no evidence of an association between the modelled pollutants (including components) investigated and STEMI but did find some evidence of a positive association between NO2 and NSTEMI. Confirmation of this association in other studies is required

Spatial patterns of the tau pathology in progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is characterized neuropathologically by neuronal loss, gliosis, and the presence of tau-immunoreactive neuronal and glial cell inclusions affecting subcortical and some cortical regions. The objectives of this study were to determine (1) the spatial patterns of the tau-immunoreactive pathology, viz., neurofibrillary tangles (NFT), oligodendroglial inclusions (GI), tufted astrocytes (TA), and Alzheimer's disease-type neuritic plaques (NP) in PSP and (2) to investigate the spatial correlations between the histological features. Post-mortem material of cortical and subcortical regions of eight PSP cases was studied. Spatial pattern analysis was applied to the NFT, GI, TA, NP, abnormally enlarged neurons (EN), surviving neurons, and glial cells. NFT, GI, and TA were distributed either at random or in regularly distributed clusters. The EN and NP were mainly randomly distributed. Clustering of NFT and EN was more frequent in the cortex and subcortical regions, respectively. Variations in NFT density were not spatially correlated with the densities of either GI or TA, but were positively correlated with the densities of EN and surviving neurons in some regions. (1) NFT were the most widespread tau-immunoreactive pathology in PSP being distributed randomly in subcortical regions and in regular clusters in cortical regions, (2) GI and TA were more localized and exhibited a regular pattern of clustering in subcortical regions, and (3) neuronal and glial cell pathologies were not spatially correlated. © 2012 Springer-Verlag

Spatiotemporal evaluation of EMEP4UK-WRF v4.3 atmospheric chemistry transport simulations of health-related metrics for NO2, O3, PM10 and PM2.5 for 2001-2010

This study was motivated by the use in air pollution epidemiology and health burden assessment of data simulated at 5 km  ×  5 km horizontal resolution by the EMEP4UK-WRF v4.3 atmospheric chemistry transport model. Thus the focus of the model–measurement comparison statistics presented here was on the health-relevant metrics of annual and daily means of NO2, O3, PM2. 5, and PM10 (daily maximum 8 h running mean for O3). The comparison was temporally and spatially comprehensive, covering a 10-year period (2 years for PM2. 5) and all non-roadside measurement data from the UK national reference monitor network, which applies consistent operational and QA/QC procedures for each pollutant (44, 47, 24, and 30 sites for NO2, O3, PM2. 5, and PM10, respectively). Two important statistics highlighted in the literature for evaluation of air quality model output against policy (and hence health)-relevant standards – correlation and bias – together with root mean square error, were evaluated by site type, year, month, and day-of-week. Model–measurement statistics were generally better than, or comparable to, values that allow for realistic magnitudes of measurement uncertainties. Temporal correlations of daily concentrations were good for O3, NO2, and PM2. 5 at both rural and urban background sites (median values of r across sites in the range 0.70–0.76 for O3 and NO2, and 0.65–0.69 for PM2. 5), but poorer for PM10 (0.47–0.50). Bias differed between environments, with generally less bias at rural background sites (median normalized mean bias (NMB) values for daily O3 and NO2 of 8 and 11 %, respectively). At urban background sites there was a negative model bias for NO2 (median NMB  =  −29 %) and PM2. 5 (−26 %) and a positive model bias for O3 (26 %). The directions of these biases are consistent with expectations of the effects of averaging primary emissions across the 5 km  ×  5 km model grid in urban areas, compared with monitor locations that are more influenced by these emissions (e.g. closer to traffic sources) than the grid average. The biases are also indicative of potential underestimations of primary NOx and PM emissions in the model, and, for PM, with known omissions in the model of some PM components, e.g. some components of wind-blown dust. There were instances of monthly and weekday/weekend variations in the extent of model–measurement bias. Overall, the greater uniformity in temporal correlation than in bias is strongly indicative that the main driver of model–measurement differences (aside from grid versus monitor spatial representivity) was inaccuracy of model emissions – both in annual totals and in the monthly and day-of-week temporal factors applied in the model to the totals – rather than simulation of atmospheric chemistry and transport processes. Since, in general for epidemiology, capturing correlation is more important than bias, the detailed analyses presented here support the use of data from this model framework in air pollution epidemiology

Traditional Cantonese diet and nasopharyngeal carcinoma risk: a large-scale case-control study in Guangdong, China

<p>Abstract</p> <p>Background</p> <p>Nasopharyngeal carcinoma (NPC) is rare in most parts of the world but is a common malignancy in southern China, especially in Guangdong. Dietary habit is regarded as an important modifier of NPC risk in several endemic areas and may partially explain the geographic distribution of NPC incidence. In China, rapid economic development during the past few decades has changed the predominant lifestyle and dietary habits of the Chinese considerably, requiring a reassessment of diet and its potential influence on NPC risk in this NPC-endemic area.</p> <p>Methods</p> <p>To evaluate the association between dietary factors and NPC risk in Guangdong, China, a large-scale, hospital-based case-control study was conducted. 1387 eligible cases and 1459 frequency matched controls were recruited. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated using a logistic regression model, adjusting for age, sex, education, dialect, and habitation household type.</p> <p>Results</p> <p>Observations made include the following: 1) consumption of canton-style salted fish, preserved vegetables and preserved/cured meat were significantly associated with increased risk of NPC, with enhanced odds ratios (OR) of 2.45 (95% CI: 2.03-2.94), 3.17(95% CI: 2.68-3.77) and 2.09 (95% CI: 1.22-3.60) respectively in the highest intake frequency stratum during childhood; 2) consumption of fresh fruit was associated with reduced risk with a dose-dependent relationship (p = 0.001); and 3) consumption of Canton-style herbal tea and herbal slow-cooked soup was associated with decreased risk, with ORs of 0.84 (95% CI: 0.68-1.03) and 0.58 (95% CI: 0.47-0.72) respectively in the highest intake frequency stratum. In multivariate analyses, these associations remained significant.</p> <p>Conclusions</p> <p>It can be inferred that previously established dietary risk factors in the Cantonese population are still stable and have contributed to the incidence of NPC.</p

Recurrent De Novo NAHR Reciprocal Duplications in the ATAD3 Gene Cluster Cause a Neurogenetic Trait with Perturbed Cholesterol and Mitochondrial Metabolism.

Recent studies have identified both recessive and dominant forms of mitochondrial disease that result from ATAD3A variants. The recessive form includes subjects with biallelic deletions mediated by non-allelic homologous recombination. We report five unrelated neonates with a lethal metabolic disorder characterized by cardiomyopathy, corneal opacities, encephalopathy, hypotonia, and seizures in whom a monoallelic reciprocal duplication at the ATAD3 locus was identified. Analysis of the breakpoint junction fragment indicated that these 67 kb heterozygous duplications were likely mediated by non-allelic homologous recombination at regions of high sequence identity in ATAD3A exon 11 and ATAD3C exon 7. At the recombinant junction, the duplication allele produces a fusion gene derived from ATAD3A and ATAD3C, the protein product of which lacks key functional residues. Analysis of fibroblasts derived from two affected individuals shows that the fusion gene product is expressed and stable. These cells display perturbed cholesterol and mitochondrial DNA organization similar to that observed for individuals with severe ATAD3A deficiency. We hypothesize that the fusion protein acts through a dominant-negative mechanism to cause this fatal mitochondrial disorder. Our data delineate a molecular diagnosis for this disorder, extend the clinical spectrum associated with structural variation at the ATAD3 locus, and identify a third mutational mechanism for ATAD3 gene cluster variants. These results further affirm structural variant mutagenesis mechanisms in sporadic disease traits, emphasize the importance of copy number analysis in molecular genomic diagnosis, and highlight some of the challenges of detecting and interpreting clinically relevant rare gene rearrangements from next-generation sequencing data

Femtosecond nonlinear ultrasonics in gold probed with ultrashort surface plasmons

Fundamental interactions induced by lattice vibrations on ultrafast time scales become increasingly important for modern nanoscience and technology. Experimental access to the physical properties of acoustic phonons in the THz frequency range and over the entire Brillouin zone is crucial for understanding electric and thermal transport in solids and their compounds. Here, we report on the generation and nonlinear propagation of giant (1 percent) acoustic strain pulses in hybrid gold/cobalt bilayer structures probed with ultrafast surface plasmon interferometry. This new technique allows for unambiguous characterization of arbitrary ultrafast acoustic transients. The giant acoustic pulses experience substantial nonlinear reshaping already after a propagation distance of 100 nm in a crystalline gold layer. Excellent agreement with the Korteveg-de Vries model points to future quantitative nonlinear femtosecond THz-ultrasonics at the nano-scale in metals at room temperature

Growth and dislocation studies of β-HMX

Background: The defect structure of organic materials is important as it plays a major role in their crystal growth properties. It also can play a subcritical role in “hot-spot” detonation processes of energetics and one such energetic is cyclotetramethylene-tetranitramine, in the commonly used beta form (β-HMX). Results: The as-grown crystals grown by evaporation from acetone show prismatic, tabular and columnar habits, all with {011}, {110}, (010) and (101) faces. Etching on (010) surfaces revealed three different types of etch pits, two of which could be identified with either pure screw or pure edge dislocations, the third is shown to be an artifact of the twinning process that this material undergoes. Examination of the {011} and {110} surfaces show only one type of etch pit on each surface; however their natural asymmetry precludes the easy identification of their Burgers vector or dislocation type. Etching of cleaved {011} surfaces demonstrates that the etch pits can be associated with line dislocations. All dislocations appear randomly on the crystal surfaces and do not form alignments characteristic of mechanical deformation by dislocation slip. Conclusions: Crystals of β-HMX grown from acetone show good morphological agreement with that predicted by modelling, with three distinct crystal habits observed depending upon the supersaturation of the growth solution. Prismatic habit was favoured at low supersaturation, while tabular and columnar crystals were predominant at higher super saturations. The twin plane in β-HMX was identified as a (101) reflection plane. The low plasticity of β-HMX is shown by the lack of etch pit alignments corresponding to mechanically induced dislocation arrays. On untwinned {010} faces, two types of dislocations exist, pure edge dislocations with b = [010] and pure screw dislocations with b = [010]. On twinned (010) faces, a third dislocation type exists and it is proposed that these pits are associated with pure screw dislocations with b = [010]