1,038 research outputs found
Extended thromboprophylaxis with betrixaban in acutely ill medical patients
BACKGROUND:
Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown.
METHODS:
Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding.
RESULTS:
A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55).
CONCLUSIONS:
Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218.)
Nucleated polymerisation in the presence of pre-formed seed filaments
We revisit the classical problem of nucleated polymerisation and derive a
range of exact results describing polymerisation in systems intermediate
between the well-known limiting cases of a reaction starting from purely
soluble material and for a reaction where no new growth nuclei are formed
The transcription factor RUNX2 regulates receptor tyrosine kinase expression in melanoma.
Receptor tyrosine kinases-based autocrine loops largely contribute to activate the MAPK and PI3K/AKT pathways in melanoma. However, the molecular mechanisms involved in generating these autocrine loops are still largely unknown. In the present study, we examine the role of the transcription factor RUNX2 in the regulation of receptor tyrosine kinase (RTK) expression in melanoma. We have demonstrated that RUNX2-deficient melanoma cells display a significant decrease in three receptor tyrosine kinases, EGFR, IGF-1R and PDGFRÎČ. In addition, we found co-expression of RUNX2 and another RTK, AXL, in both melanoma cells and melanoma patient samples. We observed a decrease in phosphoAKT2 (S474) and phosphoAKT (T308) levels when RUNX2 knock down resulted in significant RTK down regulation. Finally, we showed a dramatic up regulation of RUNX2 expression with concomitant up-regulation of EGFR, IGF-1R and AXL in melanoma cells resistant to the BRAF V600E inhibitor PLX4720. Taken together, our results strongly suggest that RUNX2 might be a key player in RTK-based autocrine loops and a mediator of resistance to BRAF V600E inhibitors involving RTK up regulation in melanoma
Radius Stabilization and Anomaly-Mediated Supersymmetry Breaking
We analyze in detail a specific 5-dimensional realization of a
"brane-universe" scenario where the visible and hidden sectors are localized on
spatially separated 3-branes coupled only by supergravity, with supersymmetry
breaking originating in the hidden sector. Although general power counting
allows order 1/M_{Planck}^2 contact terms between the two sectors in the
4-dimensional theory from exchange of supergravity Kaluza-Klein modes, we show
that they are not present by carefully matching to the 5-dimensional theory. We
also find that the radius modulus corresponding to the size of the compactified
dimension must be stabilized by additional dynamics in order to avoid run-away
behavior after supersymmetry breaking and to understand the communication of
supersymmetry breaking. We stabilize the radius by adding two pure Yang--Mills
sectors, one in the bulk and the other localized on a brane. Gaugino
condensation in the 4-dimensional effective theory generates a superpotential
that can naturally fix the radius at a sufficiently large value that
supersymmetry breaking is communicated dominantly by the recently-discovered
mechanism of anomaly mediation. The mass of the radius modulus is large
compared to m_{3/2}. The stabilization mechanism requires only parameters of
order one at the fundamental scale, with no fine-tuning except for the
cosmological constant.Comment: 20 pages, LaTeX2
Correction for Perni et al., A natural product inhibits the initiation of alpha-synuclein aggregation and suppresses its toxicity (vol 114, pg E1009, 2017)
Trodusquemine enhances Aβ42 aggregation but suppresses its toxicity by displacing oligomers from cell membranes
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Mitigation of Moral Hazard and Adverse Selection in Venture Capital Financing: The Influence of the Countryâs Institutional Setting
A venture capitalist (VC) needs to trade off benefits and costs when attempting to mitigate agency problems in their investor-investee relationship. We argue that signals of ventures complement the VCâs capacity to screen and conduct a due diligence during the pre-investment phase, but its attractiveness may diminish in institutional settings supporting greater transparency. Similarly, whereas a VC may opt for contractual covenants to curb potential opportunism by ventures in the post-investment phase, this may only be effective in settings supportive of shareholder rights enforcement. Using an international sample of VC contracts, our study finds broad support for these conjectures. It delineates theoretical and practical implications for how investors can best deploy their capital in different institutional settings whilst nurturing their relationships with entrepreneurs
A Study of Time-Dependent CP-Violating Asymmetries and Flavor Oscillations in Neutral B Decays at the Upsilon(4S)
We present a measurement of time-dependent CP-violating asymmetries in
neutral B meson decays collected with the BABAR detector at the PEP-II
asymmetric-energy B Factory at the Stanford Linear Accelerator Center. The data
sample consists of 29.7 recorded at the
resonance and 3.9 off-resonance. One of the neutral B mesons,
which are produced in pairs at the , is fully reconstructed in
the CP decay modes , , , () and , or in flavor-eigenstate
modes involving and (). The flavor of the other neutral B meson is tagged at the time of
its decay, mainly with the charge of identified leptons and kaons. The proper
time elapsed between the decays is determined by measuring the distance between
the decay vertices. A maximum-likelihood fit to this flavor eigenstate sample
finds . The value of the asymmetry amplitude is determined from
a simultaneous maximum-likelihood fit to the time-difference distribution of
the flavor-eigenstate sample and about 642 tagged decays in the
CP-eigenstate modes. We find , demonstrating that CP violation exists in the neutral B meson
system. (abridged)Comment: 58 pages, 35 figures, submitted to Physical Review
Use of Quality Improvement Strategies Among Small to Medium-Size US Primary Care Practices
PURPOSE Improving primary care quality is a national priority, but little is known about the extent to which small to medium-size practices use quality improvement (QI) strategies to improve care. We examined variations in use of QI strategies among 1,181 small to medium-size primary care practices engaged in a national initiative spanning 12 US states to improve quality of care for heart health and assessed factors associated with those variations. METHODS In this cross-sectional study, practice characteristics were assessed by surveying practice leaders. Practice use of QI strategies was measured by the validated Change Process Capability Questionnaire (CPCQ) Strategies Scale (scores range from â28 to 28, with higher scores indicating more use of QI strategies). Multivariable linear regression was used to examine the association between practice characteristics and the CPCQ strategies score. RESULTS The mean CPCQ strategies score was 9.1 (SD = 12.2). Practices that participated in accountable care organizations and those that had someone in the practice to configure clinical quality reports from electronic health records (EHRs), had produced quality reports, or had discussed clinical quality data during meetings had higher CPCQ strategies scores. Health systemâowned practices and those experiencing major disruptive changes, such as implementing a new EHR system or clinician turnover, had lower CPCQ strategies scores. CONCLUSION There is substantial variation in the use of QI strategies among small to medium-size primary care practices across 12 US states. Findings suggest that practices may need external support to strengthen their ability to do QI and to be prepared for new payment and delivery models
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