93 research outputs found

    Gásir in Eyjafjörđur: International Exchange and Local Economy in Medieval Iceland

    Get PDF
    The site of Gásir in Eyjafjörður in northeast Iceland was excavated from 2001–2006, revealing details of one of the larger seasonal trading centers of medieval Iceland. Interdisciplinary investigations of the site have shed light upon the organization of the site and provided confirmation of documentary accounts of both prestige items (gyrfalcons, walrus ivory) and bulk goods (sulphur) concentrated for export. Gásir was a major point of cultural contact as well as economic exchange between Icelanders and the world of medieval Europe, and the zooarchaeological analyses indicated a mix of foodways and the presence of exotic animals and a well-developed provisioning system, which supplied high-quality meat and fresh fish to the traders. The excavations demonstrated an unexpected regional-level economic impact of the seasonally occupied site on the surrounding rural countryside, and contribute to ongoing investigations of the extent and impact of overseas trade in medieval Iceland

    Apoptosis Governs the Elimination of Schistosoma japonicum from the Non-Permissive Host Microtus fortis

    Get PDF
    The reed vole, Microtus fortis, is the only known mammalian host in which schistosomes of Schistosoma japonicum are unable to mature and cause significant pathogenesis. However, little is known about how Schistosoma japonicum maturation (and, therefore, the development of schistosomiasis) is prevented in M. fortis. In the present study, the ultrastructure of 10 days post infection schistosomula from BALB/c mice and M. fortis were first compared using scanning electron microscopy and transmission electron microscopy. Electron microscopic investigations showed growth retardation and ultrastructural differences in the tegument and sub-tegumental tissues as well as in the parenchymal cells of schistosomula from M. fortis compared with those in BALB/c mice. Then, microarray analysis revealed significant differential expression between the schistosomula from the two rodents, with 3,293 down-regulated (by ≥2-fold) and 71 up-regulated (≥2 fold) genes in schistosomula from the former. The up-regulated genes included a proliferation-related gene encoding granulin (Grn) and tropomyosin. Genes that were down-regulated in schistosomula from M. fortis included apoptosis-inhibited genes encoding a baculoviral IAP repeat-containing protein (SjIAP) and cytokine-induced apoptosis inhibitor (SjCIAP), genes encoding molecules involved in insulin metabolism, long-chain fatty acid metabolism, signal transduction, the transforming growth factor (TGF) pathway, the Wnt pathway and in development. TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) and PI/Annexin V-FITC assays, caspase 3/7 activity analysis, and flow cytometry revealed that the percentages of early apoptotic and late apoptotic and/or necrotic cells, as well as the level of caspase activity, in schistosomula from M. fortis were all significantly higher than in those from BALB/c mice

    Prostaglandin I2 Signaling Drives Th17 Differentiation and Exacerbates Experimental Autoimmune Encephalomyelitis

    Get PDF
    BACKGROUND: Prostaglandin I(2) (PGI(2)), a lipid mediator currently used in treatment of human disease, is a critical regulator of adaptive immune responses. Although PGI(2) signaling suppressed Th1 and Th2 immune responses, the role of PGI(2) in Th17 differentiation is not known. METHODOLOGY/PRINCIPAL FINDINGS: In mouse CD4(+)CD62L(+) naïve T cell culture, the PGI(2) analogs iloprost and cicaprost increased IL-17A and IL-22 protein production and Th17 differentiation in vitro. This effect was augmented by IL-23 and was dependent on PGI(2) receptor IP signaling. In mouse bone marrow-derived CD11c(+) dendritic cells (BMDCs), PGI(2) analogs increased the ratio of IL-23/IL-12, which is correlated with increased ability of BMDCs to stimulate naïve T cells for IL-17A production. Moreover, IP knockout mice had delayed onset of a Th17-associated neurological disease, experimental autoimmune encephalomyelitis (EAE), and reduced infiltration of IL-17A-expressing mononuclear cells in the spinal cords compared to wild type mice. These results suggest that PGI(2) promotes in vivo Th17 responses. CONCLUSION: The preferential stimulation of Th17 differentiation by IP signaling may have important clinical implications as PGI(2) and its analogs are commonly used to treat human pulmonary hypertension

    Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

    Get PDF
    Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

    Energy-saving options

    No full text
    When several energy-thrift measures are implemented simultaneously in the same building, it is probable that the overall saving will be less than the sum of those expected if implemented individually, each time starting from the present situation. The relationship between such savings and capital investment has been obtained for 90 energy-saving options in total, implemented on four hospital sites. It is concluded that the financial returns on the capital expenditure are considerably enhanced by spreading the investment over several sites, rather than by investing in the relatively high rate-of-return options on only a single site.

    Optimising the choice of energy-thrift measures for hospitals

    No full text
    A programme of ninety energy-thrift recommendations, arising from energy audits undertaken for four hospital sites, have been analysed. Approximately, and in general, a law of diminishing returns exists between the magnitudes of the associated capital investments and the resulting savings accruing during the lifetimes of the investments. A simple net present value technique has been developed to maximise the savings resulting from each selected proposed investment. The optimised programme was then tested with respect to its sensitivities to over-estimated savings and under-estimated capital-cost requirements.

    Energy-signature characteristic of a hospital

    No full text
    A method for predicting the energy behaviour of a hospital complex is proposed and verified via measured data.

    Materials and retro-fit methods for reducing rates of heat loss through walls

    No full text
    Retro-fitting thermal insulation to walls has become popular, both as a [`]standalone' measure and as an integral part of building-refurbishment schemes. The benefits and disadvantages of fitting thermal insulants, either on the room side of the inner leaf, or to the [`]weather-side' of the outer leaf, or within the cavity of the exterior walls of buildings, are discussed. The effective thermal conductivities for a range of dry building materials are considered, and a [`]rule-of-thumb' equation deduced, for predicting approximately (to ±6%) the magnitude of the thermal conductivity of a dry insulating material from a knowledge of its density. Once the building is well-insulated thermally, an improvement in the effectiveness of the space-heating controls can usually further increase significantly the fuel-savings achievable, but the achievement of adequate thermal insulation should usually be the higher priority.

    Development of a high average current polarized electron source with long cathode operational lifetime

    Get PDF
    Substantially more than half of the electromagnetic nuclear physics experiments conducted at the Continuous Electron Beam Accelerator Facility of the Thomas Jefferson National Accelerator Facility (Jefferson Laboratory) require highly polarized electron beams, often at high average current. Spinpolarized electrons are produced by photoemission from various GaAs-based semiconductor photocathodes, using circularly polarized laser light with photon energy slightly larger than the semiconductor band gap. The photocathodes are prepared by activation of the clean semiconductor surface to negative electron affinity using cesium and oxidation. Historically, in many laboratories worldwide, these photocathodes have had short operational lifetimes at high average current, and have often deteriorated fairly quickly in ultrahigh vacuum even without electron beam delivery. At Jefferson Lab, we have developed a polarized electron source in which the photocathodes degrade exceptionally slowly without electron emission, and in which ion back bombardment is the predominant mechanism limiting the operational lifetime of the cathodes during electron emission. We have reproducibly obtained cathode 1/e dark lifetimes over two years, and 1/e charge density and charge lifetimes during electron beam delivery of over 2 × 105 C/cm2 and 200 C, respectively. This source is able to support uninterrupted high average current polarized beam delivery to three experimental halls simultaneously for many months at a time. Many of the techniques we report here are directly applicable to the development of GaAs photoemission electron guns to deliver high average current, high brightness unpolarized beams

    Activation of RhoA, but Not Rac1, Mediates Early Stages of S1P-Induced Endothelial Barrier Enhancement

    No full text
    <div><p>Compromised endothelial barrier function is a hallmark of inflammation. Rho family GTPases are critical in regulating endothelial barrier function, yet their precise roles, particularly in sphingosine-1-phosphate (S1P)-induced endothelial barrier enhancement, remain elusive. Confluent cultures of human umbilical vein endothelial cells (HUVEC) or human dermal microvascular endothelial cells (HDMEC) were used to model the endothelial barrier. Barrier function was assessed by determining the transendothelial electrical resistance (TER) using an electrical cell-substrate impedance sensor (ECIS). The roles of Rac1 and RhoA were tested in S1P-induced barrier enhancement. The results show that pharmacologic inhibition of Rac1 with Z62954982 failed to block S1P-induced barrier enhancement. Likewise, expression of a dominant negative form of Rac1, or knockdown of native Rac1 with siRNA, failed to block S1P-induced elevations in TER. In contrast, blockade of RhoA with the combination of the inhibitors Rhosin and Y16 significantly reduced S1P-induced increases in TER. Assessment of RhoA activation in real time using a fluorescence resonance energy transfer (FRET) biosensor showed that S1P increased RhoA activation primarily at the edges of cells, near junctions. This was complemented by myosin light chain-2 phosphorylation at cell edges, and increased F-actin and vinculin near intercellular junctions, which could all be blocked with pharmacologic inhibition of RhoA. The results suggest that S1P causes activation of RhoA at the cell periphery, stimulating local activation of the actin cytoskeleton and focal adhesions, and resulting in endothelial barrier enhancement. S1P-induced Rac1 activation, however, does not appear to have a significant role in this process.</p></div
    corecore