Connectivity differences between Gulf War Illness (GWI) phenotypes during a test of attention

One quarter of veterans returning from the 1990–1991 Persian Gulf War have developed Gulf War Illness (GWI) with chronic pain, fatigue, cognitive and gastrointestinal dysfunction. Exertion leads to characteristic, delayed onset exacerbations that are not relieved by sleep. We have modeled exertional exhaustion by comparing magnetic resonance images from before and after submaximal exercise. One third of the 27 GWI participants had brain stem atrophy and developed postural tachycardia after exercise (START: Stress Test Activated Reversible Tachycardia). The remainder activated basal ganglia and anterior insulae during a cognitive task (STOPP: Stress Test Originated Phantom Perception). Here, the role of attention in cognitive dysfunction was assessed by seed region correlations during a simple 0-back stimulus matching task (“see a letter, push a button”) performed before exercise. Analysis was analogous to resting state, but different from psychophysiological interactions (PPI). The patterns of correlations between nodes in task and default networks were significantly different for START (n = 9), STOPP (n = 18) and control (n = 8) subjects. Edges shared by the 3 groups may represent co-activation caused by the 0-back task. Controls had a task network of right dorsolateral and left ventrolateral prefrontal cortex, dorsal anterior cingulate cortex, posterior insulae and frontal eye fields (dorsal attention network). START had a large task module centered on the dorsal anterior cingulate cortex with direct links to basal ganglia, anterior insulae, and right dorsolateral prefrontal cortex nodes, and through dorsal attention network (intraparietal sulci and frontal eye fields) nodes to a default module. STOPP had 2 task submodules of basal ganglia–anterior insulae, and dorsolateral prefrontal executive control regions. Dorsal attention and posterior insulae nodes were embedded in the default module and were distant from the task networks. These three unique connectivity patterns during an attention task support the concept of Gulf War Disease with recognizable, objective patterns of cognitive dysfunction

A first direct measurement of the intergalactic medium temperature around a quasar at z=6

The thermal state of the intergalactic medium (IGM) provides an indirect probe of both the HI and HeII reionisation epochs. Current constraints on the IGM temperature from the Lya forest are restricted to the redshift range 2<z<4.5, limiting the ability to probe the thermal memory of HI reionisation toward higher redshift. In this work, we present the first direct measurement of the IGM temperature around a z=6 quasar by analysing the Doppler widths of Lya absorption lines in the proximity zone of SDSS J0818+1722. We use a high resolution (R= 40000) Keck/HIRES spectrum in combination with detailed numerical modelling to obtain the temperature at mean density, T_0=23600\pm^5000_6900K (\pm^9200_9300K) at 68 (95) per cent confidence assuming a prior probability 13500K<T_0<38500 K following HI and HeII reionisation. This enables us to place an upper limit on the redshift of HI reionisation, z_H, within 33 comoving Mpc of SDSS J0818+1722. If the quasar reionises the HeII in its vicinity, then in the limit of instantaneous reionisation we infer z_H<9.0 (11.0) at 68 (95) per cent confidence assuming photoheating is the dominant heat source and that HI reionisation is driven by ionising sources with soft spectra, typical of population II stars. If the HI and HeII in the IGM around SDSS J0818+1722 are instead reionised simultaneously by a population of massive metal-free stars, characterised by very hard ionising spectra, we obtain a tighter upper limit of z_H<8.4 (9.4). Initiating reionisation at higher redshifts produces temperatures which are too low with respect to our constraint unless the HI ionising sources or the quasar itself have spectra significantly harder than typically assumed.Comment: 15 pages, 9 figures, accepted to MNRA

Patients Recording Clinical Encounters: A Path to Empowerment? Assessment by Mixed Methods

Objective: To examine the motivations of patients recording clinical encounters, covertly or otherwise, and why some do not wish to record encounters. Design: Mixed-methods analysis of survey data and nested semistructured interviews. Setting: Survey to UK audience, using social media and radio broadcast. Participants: 168 survey respondents, of whom 161 were 18 years of age or older (130 completions). Of the 56 participants who agreed to be contacted, we included data from 17 interviews

The Holocene Paleoecology of Jenny Lake Area, Southwest Yukon, and Its Implications for Prehistory

The pollen stratigraphy of a core extracted from Jenny Lake, southwest Yukon, in 1984 has marked archaeological significance. Five palynological zones are identified as follows: Zone JL1, the oldest (ca. 12,500-9,500 B.P.), is a Betula shrub tundra assemblage; Zone JL2 (ca. 9,500-8,500 B.P.) an Alnus shrub tundra; Zone JL3 (ca. 8,500-4,500 B.P.) a Picea forest; Zone JL4 (ca. 4,500-2,000 B.P.) a Picea-Alnus woodland; and JL5 (ca. 2,000 B.P.-present) a Picea forest. The widely held belief that the Kluane-Aishihik area of the SW Yukon was covered by extensive grasslands well into the Holocene period is not supported by the palynology of the Jenny Lake Core. Instead, palynological evidence suggests that the area, which initially was a Betula shrub tundra, then Alnus shrub tundra, became a Picea-dominated forest by approximately 8,500 B.P. and remained forested to the present. The hypothesis stating early prehistoric hunters and gatherers in the SW Yukon were adapted to extensive Holocene grasslands until ca. 3,300-2,600 B.P. will have to be modified in view of these findings.Key words: Yukon, paleoecology, palynology, archaeologyMots cl&eacute;s: Yukon, pal&eacute;o&eacute;cologie, palynologie, arch&eacute;ologi

Liver Development, Regeneration, and Carcinogenesis

The identification of putative liver stem cells has brought closer the previously separate fields of liver development, regeneration, and carcinogenesis. Significant overlaps in the regulation of these processes are now being described. For example, studies in embryonic liver development have already provided the basis for directed differentiation of human embryonic stem cells and induced pluripotent stem cells into hepatocyte-like cells. As a result, the understanding of the cell biology of proliferation and differentiation in the liver has been improved. This knowledge can be used to improve the function of hepatocyte-like cells for drug testing, bioartificial livers, and transplantation. In parallel, the mechanisms regulating cancer cell biology are now clearer, providing fertile soil for novel therapeutic approaches. Recognition of the relationships between development, regeneration, and carcinogenesis, and the increasing evidence for the role of stem cells in all of these areas, has sparked fresh enthusiasm in understanding the underlying molecular mechanisms and has led to new targeted therapies for liver cirrhosis and primary liver cancers

Acanthamoeba activates macrophages predominantly through toll-like receptor 4 and MyD88-dependent mechanisms to induce Interleukin IL-12 and IL-6

Acanthamoeba castellanii is a free-living ubiquitous amoeba, with a worldwide distribution, that can occasionally infect humans, causing particularly severe infections in immune compromised individuals. Dissecting the immunology of Acanthamoeba infections has been considered problematic due to the very low incidence of disease despite the high exposure rates. Whilst macrophages are acknowledged as playing a significant role in Acanthamoeba infections little is known about how this facultative parasite influences macrophage activity. Therefore, in this study we investigate the effects of Acanthamoeba on the activation of resting macrophages. Consequently, murine bone marrow derived macrophages were co-cultured with trophozoites of either the laboratory Neff strain, or a clinical isolate of A. castellanii. In vitro real-time imaging demonstrated that trophozoites of both strains often established evanescent contact with macrophages. Both Acanthamoeba strains induced a pro-inflammatory macrophage phenotype characterized by significant production of IL-12 and IL-6. However, macrophages co-cultured with the clinical isolate of Acanthamoeba produced significantly less IL-12 and IL-6 in comparison to the Neff strain. The utilization of macrophages derived from MyD88, TRIF, TLR2, TLR4, TLR2/4 deficient mice indicated that Acanthamoeba-induced pro-inflammatory cytokine production was through MyD88-dependent, TRIF independent, TLR4-induced events. This study shows for the first time the involvement of TLRs, expressed on macrophages in the recognition and response to Acanthamoeba trophozoites

Sediment Quality in Puget Sound Year 3 - Southern Puget Sound

As a component of a three-year cooperative effort of the Washington State Department of Ecology and the National Oceanic and Atmospheric Administration, surficial sediment samples from 100 locations in southern Puget Sound were collected in 1999 to determine their relative quality based on measures of toxicity, chemical contamination, and benthic infaunal assemblage structure. The survey encompassed an area of approximately 858 km2, ranging from East and Colvos Passages south to Oakland Bay, and including Hood Canal. Toxic responses were most severe in some of the industrialized waterways of Tacoma’s Commencement Bay. Other industrialized harbors in which sediments induced toxic responses on smaller scales included the Port of Olympia, Oakland Bay at Shelton, Gig Harbor, Port Ludlow, and Port Gamble. Based on the methods selected for this survey, the spatial extent of toxicity for the southern Puget Sound survey area was 0% of the total survey area for amphipod survival, 5.7% for urchin fertilization, 0.2% for microbial bioluminescence, and 5- 38% with the cytochrome P450 HRGS assay. Measurements of trace metals, PAHs, PCBs, chlorinated pesticides, other organic chemicals, and other characteristics of the sediments, indicated that 20 of the 100 samples collected had one or more chemical concentrations that exceeded applicable, effects-based sediment guidelines and/or Washington State standards. Chemical contamination was highest in eight samples collected in or near the industrialized waterways of Commencement Bay. Samples from the Thea Foss and Middle Waterways were primarily contaminated with a mixture of PAHs and trace metals, whereas those from Hylebos Waterway were contaminated with chlorinated organic hydrocarbons. The remaining 12 samples with elevated chemical concentrations primarily had high levels of other chemicals, including bis(2-ethylhexyl) phthalate, benzoic acid, benzyl alcohol, and phenol. The characteristics of benthic infaunal assemblages in south Puget Sound differed considerably among locations and habitat types throughout the study area. In general, many of the small embayments and inlets throughout the study area had infaunal assemblages with relatively low total abundance, taxa richness, evenness, and dominance values, although total abundance values were very high in some cases, typically due to high abundance of one organism such as the polychaete Aphelochaeta sp. N1. The majority of the samples collected from passages, outer embayments, and larger bodies of water tended to have infaunal assemblages with higher total abundance, taxa richness, evenness, and dominance values. Two samples collected in the Port of Olympia near a superfund cleanup site had no living organisms in them. A weight-of-evidence approach used to simultaneously examine all three “sediment quality triad” parameters, identified 11 stations (representing 4.4 km2, 0.5% of the total study area) with sediment toxicity, chemical contamination, and altered benthos (i.e., degraded sediment quality), 36 stations (493.5 km2, 57.5% total study area) with no toxicity or chemical contamination (i.e., high sediment quality), 35 stations (274.1 km2, 32.0% total study area) with one impaired sediment triad parameter (i.e., intermediate/high sediment quality), and 18 stations (85.7km2, 10.0% total study area) with two impaired sediment parameters (i.e., intermediate/degraded quality sediments). Generally, upon comparison, the number of stations with degraded sediments based upon the sediment quality triad of data was slightly greater in the central Puget Sound than in the northern and southern Puget Sound study areas, with the percent of the total study area degraded in each region decreasing from central to north to south (2.8, 1.3 and 0.5%, respectively). Overall, the sediments collected in Puget Sound during the combined 1997-1999 surveys were among the least contaminated relative to other marine bays and estuaries studied by NOAA using equivalent methods. (PDF contains 351 pages