Multisensory visual–tactile object related network in humans: insights gained using a novel crossmodal adaptation approach

Neuroimaging techniques have provided ample evidence for multisensory integration in humans. However, it is not clear whether this integration occurs at the neuronal level or whether it reflects areal convergence without such integration. To examine this issue as regards visuo-tactile object integration we used the repetition suppression effect, also known as the fMRI-based adaptation paradigm (fMR-A). Under some assumptions, fMR-A can tag specific neuronal populations within an area and investigate their characteristics. This technique has been used extensively in unisensory studies. Here we applied it for the first time to study multisensory integration and identified a network of occipital (LOtv and calcarine sulcus), parietal (aIPS), and prefrontal (precentral sulcus and the insula) areas all showing a clear crossmodal repetition suppression effect. These results provide a crucial first insight into the neuronal basis of visuo-haptic integration of objects in humans and highlight the power of using fMR-A to study multisensory integration using non-invasinve neuroimaging techniques

Viral Protein Fragmentation May Broaden T-Cell Responses to HIV Vaccines

High mutation rates of human immunodeficiency virus (HIV) allows escape from T cell recognition preventing development of effective T cell vaccines. Vaccines that induce diverse T cell immune responses would help overcome this problem. Using SIV gag as a model vaccine, we investigated two approaches to increase the breadth of the CD8 T cell response. Namely, fusion of vaccine genes to ubiquitin to target the proteasome and increase levels of MHC class I peptide complexes and gene fragmentation to overcome competition between epitopes for presentation and recognition.three vaccines were compared: full-length unmodified SIV-mac239 gag, full-length gag fused at the N-terminus to ubiquitin and 7 gag fragments of equal size spanning the whole of gag with ubiquitin-fused to the N-terminus of each fragment. Genes were cloned into a replication defective adenovirus vector and immunogenicity assessed in an in vitro human priming system. The breadth of the CD8 T cell response, defined by the number of distinct epitopes, was assessed by IFN-γ-ELISPOT and memory phenotype and cytokine production evaluated by flow cytometry. We observed an increase of two- to six-fold in the number of epitopes recognised in the ubiquitin-fused fragments compared to the ubiquitin-fused full-length gag. In contrast, although proteasomal targeting was achieved, there was a marked reduction in the number of epitopes recognised in the ubiquitin-fused full-length gag compared to the full-length unmodified gene, but there were no differences in the number of epitope responses induced by non-ubiquitinated full-length gag and the ubiquitin-fused mini genes. Fragmentation and ubiquitination did not affect T cell memory differentiation and polyfunctionality, though most responses were directed against the Ad5 vector.Fragmentation but not fusion with ubiquitin increases the breadth of the CD8 T vaccine response against SIV-mac239 gag. Thus gene fragmentation of HIV vaccines may maximise responses

The Kuwae (Vanuatu) eruption of AD 1452: potential magnitude and volatile release

Sometime during AD 1452, according to new evidence, a large-magnitude, initially phreatomagmatic eruption, destroyed the island of Kuwae (16.83°S, 168.54°E), located in the present-day Republic of Vanuatu. It created a 12×6-km submarine caldera composed of two adjacent basins. Based on estimates of caldera volume, between 30 and 60 km3 DRE of dacite magma was ejected as pyroclastic flow and fall deposits during this event. Annual layers of ice dating from the period AD 1450–1460 contain acidity peaks representing fallout of sulfuric acid onto both the Greenland and Antarctic ice caps. These acidity peaks have been attributed by others to the sedimentation of H2SO4 aerosols that originated from sulfur degassing during the Kuwae eruption. Improved dating techniques and new data from nineteen ice cores reveal a single acidity peak attributed to Kuwae lasting from 1453 to 1457. In this study, we present new electron microprobe analyses of the S, Cl, and F contents of matrix glasses and glass inclusions in phenocrysts from tephra ejected during the Kuwae eruption. We establish that the Kuwae event did indeed yield a large release of sulfur gases. From our glass inclusion data and analysis, we calculate that the total atmospheric aerosol loading from the 1452 Kuwae eruption was ≫100 Tg H2SO4. Much of the volatile mass released during the eruption was probably contained in a separate, volatile-rich, fluid phase within the pre-eruptive Kuwae magma body. Comparing the volatile release of the Kuwae eruption with other large-magnitude eruptions, places Kuwae as the greatest sulfuric acid aerosol producer in the last seven centuries, larger even than sulfur emissions from the eruption of Tambora (Indonesia) in 1815, and possibly Laki (Iceland) in 1783. The severe and unusual climatic effects reported in the mid- to late-1450s were likely caused by the Kuwae eruption

The pharmacists' potential to provide targets for interventions to optimize pharmacotherapy in patients with asthma

<p>Background Despite of pharmacists' specialized knowledge of medication and his/her regular contact with patients, the expertise of the pharmacist may not be used enough yet. Furthermore, the potential of pharmacy dispensing data is underestimated. Objective To provide targets for tailored interventions in asthma patients and to illustrate the potential value of pharmacists in the identification of these targets using individual pharmacy dispensing data. Setting We performed a cross sectional retrospective analysis assessing the quality of asthma patients' pharmacotherapeutic treatment. Method Drug dispensing data from 2008 to 2009 were retrieved from a Dutch pharmacy database. All asthma patients were screened for potential suboptimal pharmacotherapy in 2009. Results were projected to a single community pharmacy to provide an estimate of the number of patients eligible for potential interventions. Main outcome measures (1) frequent use of short-acting beta-agonists without preventive medication, (2) concomitant use of beta-blockers, (3) multiple short courses of oral corticosteroids without using inhaled corticosteroids and 4) use of long-acting beta-agonist without inhaled corticosteroids. Results A total of 8,504 patients were eligible for analysis of the quality of their asthma treatment. 20.9 % of all asthma patients used > 100 DDD short-acting beta-agonists per year, whereas between 21.2 % (a parts per thousand yen400 DDD) and 31.4 % (100-199 DDD) of these patients did not receive preventive medication. Approximately 5.2 % of the asthma patients are using beta-blockers concomitantly and 21.8 % of them received non-cardioselective beta-blockers. 6.3 % of the asthma patients received two or more oral courses of corticosteroids in 2008 and 17.4 % of these patients did not receive inhaled corticosteroids in 2009. 2.9 % of the patients used a long-acting beta-agonists without inhaled corticosteroids. 8.4 % of the asthma patients using both long-acting beta-agonists and inhaled corticosteroids received these drugs in two separate inhalers. We estimated that about 400 asthma patients could be identified in an average pharmacy population (8,000 patients) and 33 (95 % CI 22-44) of these patients would be eligible for interventions. Conclusion This study shows the potential for pharmacists to use their own pharmacy records to identify suboptimal therapy of asthma patients, who may be targets for tailored interventions.</p>

Nature and significance of small volume fall deposits at composite volcanoes: Insights from the October 14, 1974 Fuego eruption, Guatemala

The first of four successive pulses of the 1974 explosive eruption of Fuego volcano, Guatemala, produced a small volume (∼0.02 km3 DRE) basaltic sub-plinian tephra fall and flow deposit. Samples collected within 48 h after deposition over much of the dispersal area (7–80 km from the volcano) have been size analyzed down to 8 φ (4 µm). Tephra along the dispersal axis were all well-sorted (σ φ = 0.25–1.00), and sorting increased whereas thickness and median grain size decreased systematically downwind. Skewness varied from slightly positive near the vent to slightly negative in distal regions and is consistent with decoupling between coarse ejecta falling off the rising eruption column and fine ash falling off the windblown volcanic cloud advecting at the final level of rise. Less dense, vesicular coarse particles form a log normal sub-population when separated from the smaller (Mdφ < 3φ or < 0.125 mm), denser shard and crystal sub-population. A unimodal, relatively coarse (Mdφ = 0.58φ or 0.7 mm σ φ = 1.2) initial grain size population is estimated for the whole (fall and flow) deposit. Only a small part of the fine-grained, thin 1974 Fuego tephra deposit has survived erosion to the present day. The initial October 14 pulse, with an estimated column height of 15 km above sea level, was a primary cause of a detectable perturbation in the northern hemisphere stratospheric aerosol layer in late 1974 to early 1975. Such small, sulfur-rich, explosive eruptions may substantially contribute to the overall stratospheric sulfur budget, yet leave only transient deposits, which have little chance of survival even in the recent geologic record. The fraction of finest particles (Mdφ = 4–8φ or 4–63 µm) in the Fuego tephra makes up a separate but minor size mode in the size distribution of samples around the margin of the deposit. A previously undocumented bimodal–unimodal–bimodal change in grain size distribution across the dispersal axis at 20 km downwind from the vent is best accounted for as the result of fallout dispersal of ash from a higher subplinian column and a lower “co-pf” cloud resulting from pyroclastic flows. In addition, there is a degree of asymmetry in the documented grain-size fallout pattern which is attributed to vertically veering wind direction and changing windspeeds, especially across the tropopause. The distribution of fine particles (<8 µm diameter) in the tephra deposit is asymmetrical, mainly along the N edge, with a small enrichment along the S edge. This pattern has hazard significance