Renal function at the time of a myocardial infarction maintains prognostic value for more than 10 years

<p>Abstract</p> <p>Background</p> <p>Renal function is an important predictor of mortality in patients with myocardial infarction (MI), but changes in the impact over time have not been well described.</p> <p>We examined the importance of renal function by estimated GFR (eGFR) and se-creatinine as an independent long-term prognostic factor.</p> <p>Methods</p> <p>Prospective follow-up of 6653 consecutive MI patients screened for entry in the Trandolapril Cardiac Evaluation (TRACE) study. The patients were analysed by Kaplan-Meier survival analysis, landmark analysis and Cox proportional hazard models. Outcome measure was all-cause mortality.</p> <p>Results</p> <p>An eGFR below 60 ml per minute per 1.73 m², consistent with chronic renal disease, was present in 42% of the patients. We divided the patients into 4 groups according to eGFR. Overall, Cox proportional-hazards models showed that eGFR was a significant prognostic factor in the two groups with the lowest eGFR, hazard ratio 1,72 (confidence interval (CI) 1,56-1,91) in the group with the lowest eGFR. Using the eGFR group with normal renal function as reference, we observed an incremental rise in hazard ratio. We divided the follow-up period in 2-year intervals. Landmark analysis showed that eGFR at the time of screening continued to show prognostic effect until 16 years of follow-up. By multivariable Cox regression analysis, the prognostic effect of eGFR persisted for 12 years and of se-creatinine for 10 years. When comparing the lowest group of eGFR with the group with normal eGFR, prognostic significance was present in the entire period of follow-up with a hazard ratio between 1,97 (CI 1,65-2,35) and 1,35 (CI 0,99-1,84) in the 2-year periods.</p> <p>Conclusions</p> <p>One estimate of renal function is a strong and independent long-term prognostic factor for 10-12 years following a MI.</p

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV

Listeriolysin O Is Strongly Immunogenic Independently of Its Cytotoxic Activity

The presentation of microbial protein antigens by Major Histocompatibility Complex (MHC) molecules is essential for the development of acquired immunity to infections. However, most biochemical studies of antigen processing and presentation deal with a few relatively inert non-microbial model antigens. The bacterial pore-forming toxin listeriolysin O (LLO) is paradoxical in that it is cytotoxic at nanomolar concentrations as well as being the source of dominant CD4 and CD8 T cell epitopes following infection with Listeria monocytogenes. Here, we examined the relationship of LLO toxicity to its antigenicity and immunogenicity. LLO offered to antigen presenting cells (APC) as a soluble protein, was presented to CD4 T cells at picomolar to femtomolar concentrations- doses 3000–7000-fold lower than free peptide. This presentation required a dose of LLO below the cytotoxic level. Mutations of two key tryptophan residues reduced LLO toxicity by 10–100-fold but had no effect on its presentation to CD4 T cells. Thus there was a clear dissociation between the cytotoxic properties of LLO and its very high antigenicity. Presentation of LLO to CD8 T cells was not as robust as that seen in CD4 T cells, but still occurred in the nanomolar range. APC rapidly bound and internalized LLO, then disrupted endosomal compartments within 4 hours of treatment, allowing endosomal contents to access the cytosol. LLO was also immunogenic after in vivo administration into mice. Our results demonstrate the strength of LLO as an immunogen to both CD4 and CD8 T cells

The Bandim TBscore – reliability, further development, and evaluation of potential uses

Background: The tuberculosis (TB) case detection rate has stagnated at 60% due to disorganized case finding and insensitivity of sputum smear microscopy. Of the identified TB cases, 4% die while being treated, monitored with tools that insufficiently predict failure/mortality. Objective: To explore the TBscore, a recently proposed clinical severity measure for pulmonary TB (PTB) patients, and to refine, validate, and investigate its place in case finding. Design: The TBscore's inter-observer agreement was assessed and compared to the Karnofsky Performance Score (KPS) (paper I). The TBscore's variables underlying constructs were assessed, sorting out unrelated items, proposing a more easily assessable TBscoreII, which was validated internally and externally (paper II). Finally, TBscore and TBscoreII's place in PTB-screening was examined in paper III. Results: The inter-observer variability when grading PTB patients into severity classes was moderate for both TBscore (κ W=0.52, 95% CI 0.46–0.56) and KPS (κ W=0.49, 95% CI 0.33–0.65). KPS was influenced by HIV status, whereas TBscore was unaffected by it. In paper II, proposed TBscoreII was validated internally, in Guinea-Bissau, and externally, in Ethiopia. In both settings, a failure to bring down the score by ≥25% from baseline to 2 months of treatment predicted subsequent failure (p=0.007). Finally, in paper III, TBscore and TBscoreII were assessed in health-care-seeking adults and found to be higher in PTB-diagnosed patients, 4.9 (95% CI 4.6–5.2) and 3.9 (95% CI 3.8–4.0), respectively, versus patients not diagnosed with PTB, 3.0 (95% CI 2.7–3.2) and 2.4 (95% CI 2.3–2.5), respectively. Had we referred only patients with cough >2 weeks to sputum smear, we would have missed 32.1% of the smear confirmed cases in our cohort. A TBscoreII>=2 missed 8.6%. Conclusions: TBscore and TBscoreII are useful monitoring tools for PTB patients on treatment, as they could fill the void which currently exists in risk grading of patients. They may also have a role in PTB screening; however, this requires our findings to be repeated elsewhere

Biophysical Factors Affecting the Distribution of Demersal Fish around the Head of a Submarine Canyon Off the Bonney Coast, South Australia

We sampled the demersal fish community of the Bonney Canyon, South Australia at depths (100–1,500 m) and locations that are poorly known. Seventy-eight species of demersal fish were obtained from 12 depth-stratified trawls along, and to either side, of the central canyon axis. Distributional patterns in species richness and biomass were highly correlated. Three fish assemblage groupings, characterised by small suites of species with narrow depth distributions, were identified on the shelf, upper slope and mid slope. The assemblage groupings were largely explained by depth (ρw = 0.78). Compared to the depth gradient, canyon-related effects are weak or occur at spatial or temporal scales not sampled in this study. A conceptual physical model displayed features consistent with the depth zonational patterns in fish, and also indicated that canyon upwelling can occur. The depth zonation of the fish assemblage was associated with the depth distribution of water masses in the area. Notably, the mid-slope community (1,000 m) coincided with a layer of Antarctic Intermediate Water, the upper slope community (500 m) resided within the core of the Flinders Current, and the shelf community was located in a well-mixed layer of surface water (<450 m depth)

NGF Causes TrkA to Specifically Attract Microtubules to Lipid Rafts

Membrane protein sorting is mediated by interactions between proteins and lipids. One mechanism that contributes to sorting involves patches of lipids, termed lipid rafts, which are different from their surroundings in lipid and protein composition. Although the nerve growth factor (NGF) receptors, TrkA and p75NTR collaborate with each other at the plasma membrane to bind NGF, these two receptors are endocytosed separately and activate different cellular responses. We hypothesized that receptor localization in membrane rafts may play a role in endocytic sorting. TrkA and p75NTR both reside in detergent-resistant membranes (DRMs), yet they responded differently to a variety of conditions. The ganglioside, GM1, caused increased association of NGF, TrkA, and microtubules with DRMs, but a decrease in p75NTR. When microtubules were induced to polymerize and attach to DRMs by in vitro reactions, TrkA, but not p75NTR, was bound to microtubules in DRMs and in a detergent-resistant endosomal fraction. NGF enhanced the interaction between TrkA and microtubules in DRMs, yet tyrosine phosphorylated TrkA was entirely absent in DRMs under conditions where activated TrkA was detected in detergent-sensitive membranes and endosomes. These data indicate that TrkA and p75NTR partition into membrane rafts by different mechanisms, and that the fraction of TrkA that associates with DRMs is internalized but does not directly form signaling endosomes. Rather, by attracting microtubules to lipid rafts, TrkA may mediate other processes such as axon guidance

Operation and performance of the ATLAS Tile Calorimeter in Run 1

The Tile Calorimeter is the hadron calorimeter covering the central region of the ATLAS experiment at the Large Hadron Collider. Approximately 10,000 photomultipliers collect light from scintillating tiles acting as the active material sandwiched between slabs of steel absorber. This paper gives an overview of the calorimeter’s performance during the years 2008–2012 using cosmic-ray muon events and proton–proton collision data at centre-of-mass energies of 7 and 8TeV with a total integrated luminosity of nearly 30 fb−1. The signal reconstruction methods, calibration systems as well as the detector operation status are presented. The energy and time calibration methods performed excellently, resulting in good stability of the calorimeter response under varying conditions during the LHC Run 1. Finally, the Tile Calorimeter response to isolated muons and hadrons as well as to jets from proton–proton collisions is presented. The results demonstrate excellent performance in accord with specifications mentioned in the Technical Design Report

Combined measurement of differential and total cross sections in the H → γγ and the H → ZZ* → 4ℓ decay channels at s=13 TeV with the ATLAS detector

A combined measurement of differential and inclusive total cross sections of Higgs boson production is performed using 36.1 fb−1 of 13 TeV proton–proton collision data produced by the LHC and recorded by the ATLAS detector in 2015 and 2016. Cross sections are obtained from measured H→γγ and H→ZZ*(→4ℓ event yields, which are combined taking into account detector efficiencies, resolution, acceptances and branching fractions. The total Higgs boson production cross section is measured to be 57.0−5.9 +6.0 (stat.) −3.3 +4.0 (syst.) pb, in agreement with the Standard Model prediction. Differential cross-section measurements are presented for the Higgs boson transverse momentum distribution, Higgs boson rapidity, number of jets produced together with the Higgs boson, and the transverse momentum of the leading jet. The results from the two decay channels are found to be compatible, and their combination agrees with the Standard Model predictions