Background Fibrinolytic therapy increases the risk of bleeding events. TNK-tPA (tenecteplase) is a variant of rt-PA with greater fibrin specificity and reduced plasma clearance that can be given as a ...single bolus. We compared the incidence and predictors of bleeding events after treatment with TNK-tPA and rt-PA. Methods and Results In the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT)-2 trial, 16949 patients with acute myocardial infarction were randomly assigned a single weight-adjusted bolus of TNK-tPA or a 90-min infusion of rt-PA. A total of 4·66% of patients in the TNK-tPA group experienced major non-cerebral bleeding, in comparison with 5·94% in the rt-PA group (P=0·0002). This lower rate was associated with a significant reduction in the need for blood transfusion (4·25% vs 5·49%,P =0·0003) and was consistent across subgroups. Independent risk factors for major bleeding were older age, female gender, lower body weight, enrolment in the U.S.A. and a diastolic blood pressure <70mmHg. Females at high risk (age >75 years and body weight <67kg) were less likely to have major bleeding when treated with TNK-tPA even after other risk factors were taken into account. A total of 0·93% of patients in the TNK-tPA and 0·94% of patients in the rt-PA group experienced an intracranial haemorrhage. Female patients >75 years of age who weighed <67kg tended to have lower rates of intracranial haemorrhage when treated with TNK-tPA (3/264, 1·14% vs 8/265, 3·02%). Conclusions The increased fibrin specificity and single bolus administration of TNK-tPA do not increase the risk of intracranial haemorrhage but are associated with less non-cerebral bleeding, especially amongst high-risk patients.
The Compton double-polarization observable Σ 2z has been measured for the first time in the Δ (1232) resonance region using a circularly polarized photon beam incident on a longitudinally polarized ...proton target at the Mainz Microtron. This paper reports these results, together with the model-dependent extraction of four proton spin polarizabilities from fits to additional asymmetry data using either a dispersion relation calculation or a baryon chiral perturbation theory calculations with the weighted average of these two fits resulting in γE1E1=–2.87±0.52, γM1M1=2.70±0.43, γE1M2=–0.85±0.72 , and γM1E2=2.04±0.43 , in units of 10–4 fm4 .
Remarkably little is known about metal-to-ligand charge transfer (MLCT) excited-state relaxation pathways for the ruthenium polypyridyl compounds commonly utilized in dye-sensitized solar cells. ...Herein, we report variable-temperature photoluminescence studies of compounds of the general type cis-Ru(LL)2(X)2, where LL is a bipyridyl ligand and X is CN– or NCS–, and contrast them with the well-known Ru(bpy)3 2+ and Os(bpy)3 2+, where bpy is 2,2′-bipyridine, to identify relaxation pathways. In fluid acetonitrile and propylene carbonate solutions, excited-state relaxation was found to obey a first-order kinetic model. An Arrhenius analysis revealed internal conversion to two different states, assigned to an upper MLCT excited state and a ligand field excited state. Relaxation through the upper MLCT excited state typically displayed pre-exponential factors of 107–108 s–1 with activation energies of 400–900 cm–1, while relaxation rates through ligand field states occurred with 1014–1015 s–1 and activation energies of 4000–5000 cm–1. Nonradiative decay through LF states was sensitive to the ligand identity, but in a manner that was not fully consistent with the spectrochemical series. Excited-state relaxation of cis-Ru(dcbH2)2(NCS)2, where dcbH2 is 4,4′-(CO2H)2-2,2′-bipyridine, sometimes termed N3, anchored to mesoporous TiO2 or ZrO2 thin films immersed in CH3CN occurred through the upper MLCT excited state with activational parameters in surprisingly good agreement with those abstracted from data measured in fluid solution. An important finding from these studies is that the population of dissociative ligand field excited states is unlikely to lead to unwanted photochemistry of dye-sensitized solar cells based on cis-Ru(LL)2(NCS)2-type compounds at room temperature.
The aging brain is characterized by an increased presence of neurodegenerative and vascular pathologies. However, there is substantial variation regarding the relationship between an individual's ...pathological burden and resulting cognitive impairment. To identify correlates of preserved cognitive functioning at highest age, the relationship between β-amyloid plaque load, presence of small vessel cerebrovascular disease (SVCD), iron-burden, and brain atrophy was investigated. Eighty cognitively unimpaired participants (44 oldest-old, aged 85–96 years; 36 younger-old, aged 55–80 years) were scanned by integrated positron emission tomography–magnetic resonance imaging for assessing beta regional amyloid plaque load (18F-flutemetamol), white matter hyperintensities as an indicator of SVCD (fluid-attenuated inversion recovery–magnetic resonance imaging), and iron load (quantitative susceptibility mapping). For the oldest-old group, lower cortical volume, increased β-amyloid plaque load, prevalence of SVCD, and lower cognitive performance in the normal range were found. However, compared to normal-old, cortical iron burden was lower in the oldest-old. Moreover, only in the oldest-old, entorhinal cortex volume positively correlated with β-amyloid plaque load. Our data thus indicate that the co-occurrence of aging-associated neuropathologies with reduced quantitative susceptibility mapping measures of cortical iron load constitutes a lower vulnerability to cognitive loss.
Emerging and re-emerging infections and possible bioterrorism acts will continue to challenge both the medical community and civilian populations worldwide, urging health authorities to respond ...rapidly and effectively. Established in 2005, the European Community (EC)-funded European Network of Biosafety-Level-4 laboratories (Euronet-P4), which brings together the laboratories in Porton Down, London, Hamburg, Marburg, Solna, Lyon and Rome, seeks to increase international collaboration in the areas of high containment laboratory biosafety and viral diagnostic capability, to strengthen Europe's capacity to respond to an infectious disease emergency, and to offer assistance to countries not equipped with such costly facilities. Network partners have agreed on a common strategy to fill the gaps identified in the field of risk group-4 agents’ laboratory diagnosis, namely the lack of standardization and of reference samples. The network has received a further 3-year funding, to offer assistance to external laboratories, and to start the planning of field activities.
Although titanium dioxide nanotubes (nTiO2) have been shown to improve glass ionomer cement (GIC) physicochemical properties, there is a lack of information about its biological relevance. Objective: ...To determine in vitro the impact of nTiO2 incorporated into the GIC’s matrix on the biological properties of pre-odontoblastic cells (MDPC-23).
nTiO2, synthesized by the alkaline method (≅20nm), was added to Ketac Molar EasyMix at 3%, 5%, 7% by weight and compared with unblended GIC. MDPC-23 were cultured on GIC disks added or not with nTiO2 and the following cellular parameters assessed (n=6): 1. proliferation (hemocytometer and tripan blue) (1, 3 and 4 days); 2. metabolic rate (MTT) (1, 3 and 4 days); 3. morphology (confocal microscopy) (1, 3 and 4 days); and 4. proteome (Multiplex: IL-1β, IL-6, IL-10, VEGEF and TNF) (12 and 18h). Data were submitted to generalized linear models (α=0.05).
Data analysis demonstrated that: i) cell proliferation was increased overtime regardless of the experimental group, with the n TiO2 groups displaying a significant reduction starting at 48h; ii) metabolic rate was increased overtime for the control group (no GIC), while the presence of GIC, with or without n TiO2, featured a trend towards a reduced mitochondrial metabolism; iii) in general, n TiO2 reverted the effect of CIV on the secreted levels of the evaluated proteins.
It was concluded that nTiO2 modulated the biological response of MDPC-23 cells cultured on conventional GIC disks.
VectorBase (http://www.vectorbase.org) is an NIAID-funded Bioinformatic Resource Center focused on invertebrate vectors of human pathogens. VectorBase annotates and curates vector genomes providing a ...web accessible integrated resource for the research community. Currently, VectorBase contains genome information for three mosquito species: Aedes aegypti, Anopheles gambiae and Culex quinquefasciatus, a body louse Pediculus humanus and a tick species Ixodes scapularis. Since our last report VectorBase has initiated a community annotation system, a microarray and gene expression repository and controlled vocabularies for anatomy and insecticide resistance. We have continued to develop both the software infrastructure and tools for interrogating the stored data.
PDF
