Incident venous thromboembolic events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)

<p>Background: Venous thromboembolic events (VTE), including deep venous thrombosis and pulmonary embolism, are common in older age. It has been suggested that statins might reduce the risk of VTE however positive results from studies of middle aged subjects may not be generalisable to elderly people. We aimed to determine the effect of pravastatin on incident VTE in older people; we also studied the impact of clinical and plasma risk variables.</p> <p>Methods: This study was an analysis of incident VTE using data from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), a randomized, double-blind, placebo-controlled trial of pravastatin in men and women aged 70-82. Mean follow-up was 3.2 years. Risk for VTE was examined in non-warfarin treated pravastatin (n = 2834) and placebo (n = 2865) patients using a Cox's proportional hazard model, and the impact of other risk factors assessed in a multivariate forward stepwise regression analysis. Baseline clinical characteristics, blood biochemistry and hematology variables, plasma levels of lipids and lipoproteins, and plasma markers of inflammation and adiposity were compared. Plasma markers of thrombosis and hemostasis were assessed in a nested case (n = 48) control (n = 93) study where the cohort was those participants, not on warfarin, for whom data were available.</p> <p>Results: There were 28 definite cases (1.0%) of incident VTE in the pravastatin group recipients and 20 cases (0.70%) in placebo recipients. Pravastatin did not reduce VTE in PROSPER compared to placebo [unadjusted hazard ratio (95% confidence interval) 1.42 (0.80, 2.52) p = 0.23]. Higher body mass index (BMI) [1.09 (1.02, 1.15) p = 0.0075], country [Scotland vs Netherlands 4.26 (1.00, 18.21) p = 0.050 and Ireland vs Netherlands 6.16 (1.46, 26.00) p = 0.013], lower systolic blood pressure [1.35 (1.03, 1.75) p = 0.027] and lower baseline Mini Mental State Examination (MMSE) score [1.19 (1.01, 1.41) p = 0.034] were associated with an increased risk of VTE, however only BMI, country and systolic blood pressure remained significant on multivariate analysis. In a nested case control study of definite VTE, plasma Factor VIII levels were associated with VTE [1.52 (1.01, 2.28), p = 0.044]. However no other measure of thrombosis and haemostasis was associated with increased risk of VTE.</p> <p>Conclusions: Pravastatin does not prevent VTE in elderly people at risk of vascular disease. Blood markers of haemostasis and inflammation are not strongly predictive of VTE in older age however BMI, country and lower systolic blood pressure are independently associated with VTE risk.</p&gt

Cluster-randomized trial of a web-assisted tobacco quality improvement intervention of subsequent patient tobacco product use: A national dental PBRN study

ABSTRACT: BACKGROUND: Brief clinician delivered advice helps in tobacco cessation efforts. This study assessed the impact of our intervention on instances of advice given to dental patients during visits on tobacco use quit rates 6 months after the intervention. METHODS: The intervention was cluster randomized trial at the dental practice level. Intervention dental practices were provided a longitudinal technology-assisted intervention, oralcancerprevention.org that included a series of interactive educational cases and motivational email cues to remind dental provides to complete guideline-concordant brief behavioral counseling at the point of care. In all dental practices, exit cards were given to the first 100 consecutive patients, in which tobacco users provided contact information for a six month follow-up telephone survey. RESULTS: A total of 564 tobacco using dental patients completed a six month follow-up survey. Among intervention patients, 55% reported receiving advice to quit tobacco, and 39% of control practice patients reported receiving advice to quit tobacco (p \u3c 0.01). Six-month tobacco use quit rates were not significantly between the Intervention (9%) and Control (13%) groups, (p = 0.088). CONCLUSION: Although we increased rates of cessation advice delivered in dental practices, this study shows no evidence that brief advice by dentist\u27s increases long-term abstinence in smokers.Trial registration: ClinicalTrials.gov NCT00627185

A better life through information technology? The techno-theological eschatology of posthuman speculative science

This is the pre-peer reviewed version of the article, published in Zygon 41(2) pp.267-288, which has been published in final form at http://www3.interscience.wiley.com/journal/118588124/issueThe depiction of human identity in the pop-science futurology of engineer/inventor Ray Kurzweil, the speculative-robotics of Carnegie Mellon roboticist Hans Moravec and the physics of Tulane University mathematics professor Frank Tipler elevate technology, especially information technology, to a point of ultimate significance. For these three figures, information technology offers the potential means by which the problem of human and cosmic finitude can be rectified. Although Moravec’s vision of intelligent robots, Kurzweil’s hope for immanent human immorality, and Tipler’s description of human-like von Neumann probe colonising the very material fabric of the universe, may all appear to be nothing more than science fictional musings, they raise genuine questions as to the relationship between science, technology, and religion as regards issues of personal and cosmic eschatology. In an attempt to correct what I see as the ‘cybernetic-totalism’ inherent in these ‘techno-theologies’, I will argue for a theology of technology, which seeks to interpret technology hermeneutically and grounds human creativity in the broader context of divine creative activity

Adaptation of the Basic Empathy Scale among a Portuguese sample of incarcerated juvenile offenders

The main aim of the present study was to examine the psychometric properties of the Basic Empathy Scale (BES) and of its adapted short version among a forensic sample of incarcerated male juvenile offenders (N = 221). The Portuguese validations of the BES and its adapted short version demonstrated good psychometric properties, namely in terms of the two-factor structure, internal consistency, convergent validity, discriminant validity, and concurrent validity that generally justifies its use among this population. Statistically significant associations were found with callous– unemotional traits and social anxiety. Findings are discussed in terms of the use of the BES and its adapted short version with juvenile offenders.This research was supported by the Portuguese Foundation for Science and Technology (FCT) with co-financing of the European Social Fund – POPH/FSE [grant number SFRH/BPD/86666/2012]

Effects of S1 Cleavage on the Structure, Surface Export, and Signaling Activity of Human Notch1 and Notch2

Notch receptors are normally cleaved during maturation by a furin-like protease at an extracellular site termed S1, creating a heterodimer of non-covalently associated subunits. The S1 site lies within a key negative regulatory region (NRR) of the receptor, which contains three highly conserved Lin12/Notch repeats and a heterodimerization domain (HD) that interact to prevent premature signaling in the absence of ligands. Because the role of S1 cleavage in Notch signaling remains unresolved, we investigated the effect of S1 cleavage on the structure, surface trafficking and ligand-mediated activation of human Notch1 and Notch2, as well as on ligand-independent activation of Notch1 by mutations found in human leukemia.The X-ray structure of the Notch1 NRR after furin cleavage shows little change when compared with that of an engineered Notch1 NRR lacking the S1-cleavage loop. Likewise, NMR studies of the Notch2 HD domain show that the loop containing the S1 site can be removed or cleaved without causing a substantial change in its structure. However, Notch1 and Notch2 receptors engineered to resist S1 cleavage exhibit unexpected differences in surface delivery and signaling competence: S1-resistant Notch1 receptors exhibit decreased, but detectable, surface expression and ligand-mediated receptor activation, whereas S1-resistant Notch2 receptors are fully competent for cell surface delivery and for activation by ligands. Variable dependence on S1 cleavage also extends to T-ALL-associated NRR mutations, as common class 1 mutations display variable decrements in ligand-independent activation when introduced into furin-resistant receptors, whereas a class 2 mutation exhibits increased signaling activity.S1 cleavage has distinct effects on the surface expression of Notch1 and Notch2, but is not generally required for physiologic or pathophysiologic activation of Notch proteins. These findings are consistent with models for receptor activation in which ligand-binding or T-ALL-associated mutations lead to conformational changes of the NRR that permit metalloprotease cleavage

Combined proteome and transcriptome analyses for the discovery of urinary biomarkers for urothelial carcinoma

Background: Proteomic discovery of cancer biomarkers in body fluids is challenging because of their low abundance in a complex background. Altered gene expression in tumours may not reflect protein levels in body fluids. We have tested combining gene expression profiling of tumours with proteomic analysis of cancer cell line secretomes as a strategy to discover urinary biomarkers for bladder cancer. Methods: We used shotgun proteomics to identify proteins secreted by three bladder cancer cell lines. Secreted proteins with high mRNA levels in bladder tumours relative to normal urothelium were assayed by ELISA in urine samples from 642 patients. Results: Midkine and HAI-1 were significantly increased in bladder cancer patients, with the highest levels in invasive disease (area under the receiver operating characteristic curve 0.89 vs non-cancer). The urinary concentration of both proteins was too high to be explained by bladder cancer associated haematuria and most likely arises by direct tumour secretion. Conclusions: This ‘dual-omic’ strategy identified tumour secreted proteins whose urine concentrations are increased significantly by bladder cancer. Combined secretome-transcriptome analysis may be more useful than direct proteomic analysis of body fluids for biomarker discovery in both bladder cancer and other tumour type

Studies of di-jet survival and surface emission bias in Au+Au collisions via angular correlations with respect to back-to-back leading hadrons

We report first results from an analysis based on a new multi-hadron correlation technique, exploring jet-medium interactions and di-jet surface emission bias at RHIC. Pairs of back-to-back high transverse momentum hadrons are used for triggers to study associated hadron distributions. In contrast with two- and three-particle correlations with a single trigger with similar kinematic selections, the associated hadron distribution of both trigger sides reveals no modification in either relative pseudo-rapidity or relative azimuthal angle from d+Au to central Au+Au collisions. We determine associated hadron yields and spectra as well as production rates for such correlated back-to-back triggers to gain additional insights on medium properties.Comment: By the STAR Collaboration. 6 pages, 2 figure