Chemokines and alcoholic liver disease

Alcoholic liver disease is characterised by infiltration of the liver with leucocytes; alcoholic hepatitis is characterised by a neutrophil infiltrate whilst both hepatitis and cirrhosis are characterised by monocytic and lymphocytic infiltration. Chemokines are chemoattractant molecules that regulate leueocyte adhesion and migration at sites of tissue damage. In this thesis I studied the hypothesis that chemokines regulate the leucocyte infiltration and tissue damage characteristic of alcoholic liver disease and thereby determine the nature of the liver damage. Immunohistochemical and in situ hybridisation demonstrated increased expression of several chemokines in alcoholic liver disease. The neutrophil chemokine IL-8 and the lymphoeyte and monocyte ehemokines MCP-1, MIP-1α and MIP-1β were present throughout the hepatic acinus in patterns corresponding to the severity of infiltration with these leucocytes. Chemokine mRNA was mainly localised to non-parenchymal eells including sinusoidal cells, fibroblasts and infiltrating leueocytes. In patients with alcoholic liver disease, circulating serum levels of the ehemokine MCP-1 were raised compared to healthy controls and in proportion to histological severity of liver disease. Peripheral mononuclear cell secretion of both MCP-1 and MIP-1α were raised in alcoholic hepatitis with evidence for both liver-derived and circulating monocyte-derived synthesis. In vitro studies with radiolabelled chemokine protein demonstrated uptake of chemokines into isolated hepatocytes from surrounding culture medium, with uptake increased by the addition of alcohol or the pro-inflammatory cytokine TNF-α. Uptake was predominantly by low-affinity receptors but immunohistochemical studies suggest that specific receptors may nevertheless be up-regulated in alcoholic liver disease. Secretion of the chemokine MCP-1 from peripheral mononuclear cells and hepatocytes in vitro was diminished by alcohol or acetaldehyde with a dose-dependent effect. However, an ex vivo study in healthy volunteers showed that mononuclear cell secretion of MCP-1 may be increased when alcohol is ingested together with a balanced meal. An uncontrolled pilot study of the xanthine-derivative pentoxifylline in subjects with severe alcoholic hepatitis, together with in vitro studies of its effect upon chemokine seeretion, showed that this agent may have a role in the treatment of the disease. In a controlled study examining genetic predisposition to symptomatic alcoholic liver disease, we examined two TNF-α promoter polymorphisms and HLA haplotypes DR3 and DQ2; however we failed to show any associations between these markers and the disease

Axial Load Capacity of Sheeted C and Z Members

An equation is developed for calculating the axial load capacity of C and Z shaped members used in roof or wall systems. The equations were determined to be valid for through fastened metal decking but not standing seam roof decking

Investigating the veracity of a sample of divergent published trial data in spinal pain

Evidence-based medicine is replete with studies assessing quality and bias, but few evaluating research integrity or trustworthiness. A recent Cochrane review of psychological interventions for chronic pain identified trials with a shared lead author with highly divergent results. We sought to systematically identify all similar trials from this author to explore their risk of bias, governance procedures, and trustworthiness. We searched OVID MEDLINE, EMBASE, CENTRAL, and PEDro from 2010 to December 22, 2021 for trials. We contacted the authors requesting details of trial registration, ethical approval, protocol, and access to the trial data for verification. We used the Cochrane risk-of-bias tool and the Cochrane Pregnancy and Childbirth group's Trustworthiness Screening Tool to guide systematic exploration of trustworthiness. Ten trials were included: 9 compared cognitive behavioural therapy and physical exercise to usual care, exercise alone, or physiotherapy and 1 compared 2 brief cognitive behavioural therapy programmes. Eight trials reported results divergent from the evidence base. Assessment of risk of bias and participant characteristics identified no substantial concerns. Responses from the lead author did not satisfactorily explain this divergence. Trustworthiness screening identified concerns about research governance, data plausibility at baseline, the results, and apparent data duplication. We discuss the findings within the context of methods for establishing the trustworthiness of research findings generally. Important concerns regarding the trustworthiness of these trials reduce our confidence in them. They should probably not be used to inform the results and conclusions of systematic reviews, in clinical training, policy documents, or any relevant instruction regarding adult chronic pain management

Hydrothermal pits in the biogenic sediments of the equatorial Pacific Ocean

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95123/1/ggge1033.pd

Transmission of High-Power Electron Beams Through Small Apertures

Tests were performed to pass a 100 MeV, 430 kWatt c.w. electron beam from the energy-recovery linac at the Jefferson Laboratory's FEL facility through a set of small apertures in a 127 mm long aluminum block. Beam transmission losses of 3 p.p.m. through a 2 mm diameter aperture were maintained during a 7 hour continuous run.Comment: arXiv admin note: text overlap with arXiv:1305.019

Measured Radiation and Background Levels During Transmission of Megawatt Electron Beams Through Millimeter Apertures

We report measurements of photon and neutron radiation levels observed while transmitting a 0.43 MW electron beam through millimeter-sized apertures and during beam-off, but accelerating gradient RF-on, operation. These measurements were conducted at the Free-Electron Laser (FEL) facility of the Jefferson National Accelerator Laboratory (JLab) using a 100 MeV electron beam from an energy-recovery linear accelerator. The beam was directed successively through 6 mm, 4 mm, and 2 mm diameter apertures of length 127 mm in aluminum at a maximum current of 4.3 mA (430 kW beam power). This study was conducted to characterize radiation levels for experiments that need to operate in this environment, such as the proposed DarkLight Experiment. We find that sustained transmission of a 430 kW continuous-wave (CW) beam through a 2 mm aperture is feasible with manageable beam-related backgrounds. We also find that during beam-off, RF-on operation, multipactoring inside the niobium cavities of the accelerator cryomodules is the primary source of ambient radiation when the machine is tuned for 130 MeV operation.Comment: 9 pages, 11 figures, submitted to Nuclear Instruments and Methods in Physics Research Section