Lipopolysaccharide (LPS)-binding protein is carried on lipoproteins and acts as a cofactor in the neutralization of LPS.

Lipoproteins isolated from normal human plasma can bind and neutralize bacterial lipopolysaccharide (LPS) and may represent an important mechanism in host defense against gram-negative septic shock. Recent studies have shown that experimentally elevating the levels of circulating high-density lipoproteins (HDL) provides protection against death in animal models of endotoxic shock. We sought to define the components of HDL that are required for neutralization of LPS. To accomplish this we have studied the functional neutralization of LPS by native and reconstituted HDL using a rapid assay that measures the CD14-dependent activation of leukocyte integrins on human neutrophils. We report here that reconstituted HDL particles (R-HDL), prepared from purified apolipoprotein A-I (apoA-I) combined with phospholipid and free cholesterol, are not sufficient to neutralize the biologic activity of LPS. However, addition of recombinant LPS binding protein (LBP), a protein known to transfer LPS to CD14 and enhance responses of cells to LPS, enabled prompt binding and neutralization of LPS by R-HDL. Thus, LBP appears capable of transferring LPS not only to CD14 but also to lipoprotein particles. In contrast with R-HDL, apoA-I containing lipoproteins (LpA-I) isolated from plasma by selected affinity immunosorption (SAIS) on an anti-apoA-I column, neutralized LPS without addition of exogenous LBP. Several lines of evidence demonstrated that LBP is a constituent of LpA-I in plasma. Passage of plasma over an anti-apoA-I column removed more than 99% of the LBP detectable by ELISA, whereas 31% of the LBP was recovered by elution of the column. Similarly, the ability of plasma to enable activation of neutrophils by LPS (LBP/Septin activity) was depleted and recovered by the same process. Furthermore, an immobilized anti-LBP monoclonal antibody coprecipitated apoA-I. The results described here suggest that in addition to its ability to transfer LPS to CD14, LBP may also transfer LPS to lipoproteins. Since LBP appears to be physically associated with lipoproteins in plasma, it is positioned to play an important role in the neutralization of LPS

Glycoprotein IIb/IIIa Inhibitors Use and Outcome after Percutaneous Coronary Intervention for Non-ST Elevation Myocardial Infarction

Aims. We investigate the effect of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors on long-term outcomes following percutaneous coronary intervention (PCI) after non-ST elevation myocardial infarction (NSTEMI). Meta-analyses indicate that these agents are associated with improved short-term outcomes. However, many trials were undertaken before the routine use of P2Y12 inhibitors. Recent studies yield conflicting results and registry data have suggested that GP IIb/IIIa inhibitors may cause more bleeding than what trials indicate. Methods and Results. This retrospective observational study involves 3047 patients receiving dual-antiplatelet therapy who underwent PCI for NSTEMI. Primary outcome was all-cause mortality. Major adverse cardiac events (MACE) were a secondary outcome. Mean follow-up was 4.6 years. Patients treated with GP IIb/IIIa inhibitors were younger with fewer comorbidities. Although the unadjusted Kaplan-Meier analysis suggested that GP IIb/IIIa inhibitor use was associated with improved outcomes, multivariate analysis (including propensity scoring) showed no benefit for either survival (P=0.136) or MACE (P=0.614). GP IIb/IIIa inhibitor use was associated with an increased risk of major bleeding (P=0.021). Conclusion. Although GP IIb/IIIa inhibitor use appeared to improve outcomes after PCI for NSTEMI, patients who received GP IIb/IIIa inhibitors tended to be at lower risk. After multivariate adjustment we observed no improvement in MACE or survival and an increased risk of major bleeding

Medium-term follow-up of Crohn's disease in Cape Town

The 82 cases of Crohn's disease diagnosed in Greater Cape Town between 1970 and 1979 were followed up after a median time. of 9,6 years from diagnosis. Sixty patients were contacted; 6 had died and 16 were not available for followup. Only 1 death was disease-related. Mortality in Crohn's disease was not increased. There were no cases of carcinoma of the colon. At diagnosis most patients had had moderately severe disease, and 10 years later, 80% had mild-to-moderate symptoms. The 5-year resection rate was 46% and the 10-year rate 68%; 23% of patients required a second resection within 5 years of the first, and 42% within 10 years. Surgery occurred earlier in those with ileitis. Ten patients were over the age of 60 years at diagnosis; there was no apparent difference between the extent of their disease and that in the group as a whole. However, the elderly patients appeared to have a better prognosis - 59% having been symptom-free for more than 1 year, and none having required a second resection.S Afr Med J 1989; 76: 139-14

Medium-term follow-up of ulcerative colitis in Cape Town

The 114 patients with ulcerative colitis diagnosed in Greater Cape Town between 1970 and 1979 were followed up 11 years later. Ninety per cent of those contacted were in remission or had mild symptoms only. Eleven patients had died; 3 deaths (in total colitis patients) were disease-related but the overall mortality rate in ulcerative colitis was not increased. There was only 1 case of carcinoma of the colon. The 5-year surgical rate was 5% increasing to 23% 10 years after diagnosis. Six patients (35%) had had a Park's pouch, 3 (18%) ileorectal anastomosis, and a (47%) panproctocolectomy or colectomy with an ileostomy. The incidence of surgery was higher in those with total colitis. In those patients who did not have the rectum removed, there was a 100% recurrence of proctitis. Park's pouch patients remained well and incontinence was not a problem. Thirty-one per cent of patients with proctitis at diagnosis had evidence of extension of disease to the colon at follow-up. Ulcerative colitis may be a more benign disease than often believed, with mortality from the disease and need for surgery being associated almost exclusively with extensive disease.S Afr Med J 1989; 76: 142·14

The Relationship Between HR Practices and Firm Performance: Examining Causal Order

Significant research attention has been devoted to examining the relationship between HR practices and firm performance, and the research support has assumed HR as the causal variable. Using data from 45 business units (with 62 data points), this study examines how measures of HR practices correlate with past, concurrent, and future operational performance measures. The results indicate that correlations with performance measures at all three times are both high and invariant, and that controlling for past or concurrent performance virtually eliminates the correlation of HR with future performance. Implications are discussed

A Study of the Effects of Position Resolution and Energy Resolution on Compton Imaging using a Single Planar Strip Detector

The feasibility of single element Compton imaging using a Double Sided Germanium Strip Detector (DSGSD) has been investigated, with potential use in assisting particle identification as part of Phase III DEGAS at DESPEC in mind. DEGAS is a proposed high-purity germanium tracking array for use in the DEcay SPECtroscopy (DESPEC) experiment at FAIR. The concept of γ-ray tracking within a DSGSD has been proved viable, with Compton images reconstructed from partial energy depositions within the detector volume. Using the raw positional information provided by the segmentation of the detector, initial source locations were unable to be resolved, with the resulting image displaying multiple ‘hotspots’ resulting from the selection criteria imposed. The causes of these features have been explored and explained in terms of scattering angles using the simulation package GAMOS. The effects of Pulse Shape Analysis, as a means of improving position sensitivity, have also been investigated, using a simulated database in con- junction with a grid search algorithm. Detailed electric field simulations were created, enabling a simulated pulse shape database to be generated using the ADL software package. Experimental data were sorted to locate potential Compton events, with charge pulses for each events stored using a digital electronics setup. Experimental pulses were compared to pulses from the simulated database using a FoM minimisation grid search algorithm. This improved the position resolution of interactions within the detector, thus improving the effectiveness of the resulting Compton reconstructions. With the application of PSA, initial source positions were located to within ∼ 10 mm, with the image resolution found to be of the order ∼ 100 mm for a range of initial γ-ray energies. Initial results appear promising, with future work required to improve the efficiency of the method. Additionally, Monte Carlo simulations have been performed to study the individual contributions of both energy and position resolution on the final reconstructed Compton image. Simulations were performed for three energy resolutions; 0, 3 and 50 keV, with a fixed position resolution of 2 × 2 × 10 mm, in addition to three position resolutions; 1, 2 and 5 mm3, with a fixed energy resolution of 5 keV. The results of these showed that the position sensitivity of the detector has a much more significant impact of both the location and resolution of the reconstructed Compton image

Electromechanical Response of Polycrystalline Barium Titanate Resolved at the Grain Scale

Ferroic materials are critical components in many modern devices. Polycrystalline states of these materials dominate the market due to their cost effectiveness and ease of production. Studying the coupling of ferroic properties across grain boundaries and within clusters of grains is therefore critical for understanding bulk polycrystalline ferroic behavior. Here, three-dimensional X-ray diffraction is used to reconstruct a 3D grain map (grain orientations and neighborhoods) of a polycrystalline barium titanate sample and track the grain-scale non-180° ferroelectric domain switching strains of 139 individual grains in situ under an applied electric field. The map shows that each grain is located in a very unique local environment in terms of intergranular misorientations, leading to local strain heterogeneity in the as-processed state of the sample. While primarily dependent on the crystallographic orientation relative to the field directions, the response of individual grains is also heterogeneous. These unique experimental results are of critical importance both when building the starting conditions and considering the validity of grain-scale modeling efforts, and provide additional considerations in the design of novel ferroic materials

Effect of once-only flexible sigmoidoscopy screening on the outcomes of subsequent faecal occult blood test screening

Objectives: To investigate the outcomes of biennial guaiac faecal occult blood test (gFOBT) screening after once-only flexible sigmoidoscopy (FS) screening. Methods: Between 1994 and 1999, as part of the UK FS Screening Trial (UKFSST), adults aged 55-64 years were randomly allocated to an intervention group (offered FS screening) or a control group (not contacted). From 2006, a subset of UKFSST participants (20,895/44,041 intervention group; 41,497/87,149 control group) were invited to biennial gFOBT screening by the English Bowel Cancer Screening Programme. We analysed gFOBT uptake, test positivity, yield of colorectal cancer (CRC), and positive predictive value (PPV) for CRC, advanced adenomas (AA), and advanced colorectal neoplasia (ACN: AA/CRC). Results: Uptake of gFOBT at first invite was 1.9% lower (65.7% vs. 67.6%, p<0.01) among intervention versus control group participants; positivity was 0.4% lower (2.0% vs. 2.4%, p<0.01); and CRC yield was 0.08% lower (0.19% vs. 0.27%, p=0.14). PPVs were also lower in the intervention versus control group at 10.3% vs. 12.3% (p=0.44) for CRC, 22.7% vs. 31.4% (p<0.01) for AA, and 33.0% vs. 43.7% (p<0.01) for ACN. Among those who refused FS (n=5,532), gFOBT uptake at first invite was 47.7%, CRC yield was 0.25%, and PPV for ACN was 46.2%; among FS attenders (n=15,363), uptake was 72.2%, CRC yield was 0.18%, and PPV for ACN was 27.9%. Conclusions: Uptake, positivity and PPV of gFOBT screening were reduced following prior offer of FS screening. However, a quarter of FS screened participants receiving a diagnostic examination after positive gFOBT were diagnosed with ACN