Hydrophobic cis-platinum complexes efficiently incorporated into liposomes

The present invention involves the synthesis and use of new platinum compounds. These new platinum compounds are easy to encapsulate in liposomes at high efficiencies. They are further characterized as platinum (II) four coordinate complex having the formula: ##STR1## wherein R.sub.1 and R.sub.2 are carboxylato monoanions bearing a hydrophobic radical function or a single carboxylato dianion bearing a hydrophobic radical function and R.sub.3 is a vicinal diaminoalkane or vicinal diaminocycloalkane. The complex is substantially soluble in methanol or chloroform and substantially insoluble in water. Said complex may be incorporated into phospholipid liposomes. Such platinum complexes encapsulated in phospholipid liposomes are useful for chemotherapy of platinum complex-sensitive tumors.Board of Regents, University of Texas Syste

Modeling an aerobic biotrickling filter for biogas desulfurization through a multi-step oxidation mechanism

Peer ReviewedPostprint (author's final draft

Covariate-adjusted analysis of the Phase 3 REFLECT study of lenvatinib versus sorafenib in the treatment of unresectable hepatocellular carcinoma.

BACKGROUND: In the Phase 3 REFLECT trial in patients with unresectable hepatocellular carcinoma (uHCC), the multitargeted tyrosine kinase inhibitor, lenvatinib, was noninferior to sorafenib in the primary outcome of overall survival. Post-hoc review revealed imbalances in prognostic variables between treatment arms. Here, we re-analyse overall survival data from REFLECT to adjust for the imbalance in covariates. METHODS: Univariable and multivariable adjustments were undertaken for a candidate set of covariate values that a physician panel indicated could be prognostically associated with overall survival in uHCC. The values included baseline variables observed pre- and post-randomisation. Univariable analyses were based on a stratified Cox model. The multivariable analysis used a "forwards stepwise" Cox model. RESULTS: Univariable analysis identified alpha-fetoprotein (AFP) as the most influential variable. The chosen multivariable Cox model analysis resulted in an estimated adjusted hazard ratio for lenvatinib of 0.814 (95% CI: 0.699-0.948) when only baseline variables were included. Adjusting for post-randomisation treatment variables further increased the estimated superiority of lenvatinib. CONCLUSIONS: Covariate adjustment of REFLECT suggests that the original noninferiority trial likely underestimated the true effect of lenvatinib on overall survival due to an imbalance in baseline prognostic covariates and the greater use of post-treatment therapies in the sorafenib arm. TRIAL REGISTRATION: Trial number: NCT01761266 (Submitted January 2, 2013)

High precision X-ray logN-logS distributions: implications for the obscured AGN population

We have constrained the extragalactic source count distributions over a broad range of X-ray fluxes and in various energy bands to test whether the predictions from X-ray background synthesis models agree with the observational constraints provided by our measurements. We have used 1129 XMM-Newton observations at |b|>20 deg covering a sky area of 132.3 deg^2 to compile the largest complete samples of X-ray objects to date in the 0.5-1 keV, 1-2 keV, 2-4.5 keV, 4.5-10 keV, 0.5-2 keV and 2-10 keV energy bands. Our survey includes in excess of 30,000 sources down to ~10^-15 erg/cm^2/s below 2 keV and down to ~10^{-14} erg/cm^2/s above 2 keV. A break in the source count distributions was detected in all energy bands except the 4.5-10 keV band. An analytical model comprising 2 power-law components cannot adequately describe the curvature seen in the source count distributions. The shape of the logN(>S)-logS is strongly dependent on the energy band with a general steepening apparent as we move to higher energies. This is due to non-AGN populations, comprised mainly of stars and clusters of galaxies, contribute up to 30% of the source population at energies 10^{-13} erg/cm^2/s, and these populations of objects have significantly flatter source count distributions than AGN. We find a substantial increase in the relative fraction of hard X-ray sources at higher energies, from >55% below 2 keV to >77% above 2 keV. However the majority of sources detected above 4.5 keV still have significant flux below 2 keV. Comparison with predictions from the synthesis models suggest that the models might be overpredicting the number of faint absorbed AGN, which would call for fine adjustment of some model parameters such as the obscured to unobscured AGN ratio and/or the distribution of column densities at intermediate obscuration.Comment: Accepted for publication in Astronomy and Astrophysics. Abridged Abstract. 23 pages, 47 figures, 8 table

International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB)

Abstract Position Statement: The International Society of Sports Nutrition (ISSN) bases the following position stand on a critical analysis of the literature on the use of beta-hydroxy-beta-methylbutyrate (HMB) as a nutritional supplement. The ISSN has concluded the following. 1. HMB can be used to enhance recovery by attenuating exercise induced skeletal muscle damage in trained and untrained populations. 2. If consuming HMB, an athlete will benefit from consuming the supplement in close proximity to their workout. 3. HMB appears to be most effective when consumed for 2 weeks prior to an exercise bout. 4. Thirty-eight mg·kg·BM-1 daily of HMB has been demonstrated to enhance skeletal muscle hypertrophy, strength, and power in untrained and trained populations when the appropriate exercise prescription is utilized. 5. Currently, two forms of HMB have been used: Calcium HMB (HMB-Ca) and a free acid form of HMB (HMB-FA). HMB-FA may increase plasma absorption and retention of HMB to a greater extent than HMB-CA. However, research with HMB-FA is in its infancy, and there is not enough research to support whether one form is superior. 6. HMB has been demonstrated to increase LBM and functionality in elderly, sedentary populations. 7. HMB ingestion in conjunction with a structured exercise program may result in greater declines in fat mass (FM). 8. HMB’s mechanisms of action include an inhibition and increase of proteolysis and protein synthesis, respectively. 9. Chronic consumption of HMB is safe in both young and old populations

An Unusual Transmission Spectrum for the Sub-Saturn KELT-11b Suggestive of a Sub-Solar Water Abundance

We present an optical-to-infrared transmission spectrum of the inflated sub-Saturn KELT-11b measured with the Transiting Exoplanet Survey Satellite (TESS), the Hubble Space Telescope (HST) Wide Field Camera 3 G141 spectroscopic grism, and the Spitzer Space Telescope (Spitzer) at 3.6 $\mu$m, in addition to a Spitzer 4.5 $\mu$m secondary eclipse. The precise HST transmission spectrum notably reveals a low-amplitude water feature with an unusual shape. Based on free retrieval analyses with varying molecular abundances, we find strong evidence for water absorption. Depending on model assumptions, we also find tentative evidence for other absorbers (HCN, TiO, and AlO). The retrieved water abundance is generally $\lesssim 0.1\times$ solar (0.001--0.7$\times$ solar over a range of model assumptions), several orders of magnitude lower than expected from planet formation models based on the solar system metallicity trend. We also consider chemical equilibrium and self-consistent 1D radiative-convective equilibrium model fits and find they too prefer low metallicities ($[M/H] \lesssim -2$, consistent with the free retrieval results). However, all the retrievals should be interpreted with some caution since they either require additional absorbers that are far out of chemical equilibrium to explain the shape of the spectrum or are simply poor fits to the data. Finally, we find the Spitzer secondary eclipse is indicative of full heat redistribution from KELT-11b's dayside to nightside, assuming a clear dayside. These potentially unusual results for KELT-11b's composition are suggestive of new challenges on the horizon for atmosphere and formation models in the face of increasingly precise measurements of exoplanet spectra.Comment: Accepted to The Astronomical Journal. 31 pages, 20 figures, 7 table

Paraneoplastic thrombocytosis in ovarian cancer

<p>Background: The mechanisms of paraneoplastic thrombocytosis in ovarian cancer and the role that platelets play in abetting cancer growth are unclear.</p> <p>Methods: We analyzed clinical data on 619 patients with epithelial ovarian cancer to test associations between platelet counts and disease outcome. Human samples and mouse models of epithelial ovarian cancer were used to explore the underlying mechanisms of paraneoplastic thrombocytosis. The effects of platelets on tumor growth and angiogenesis were ascertained.</p> <p>Results: Thrombocytosis was significantly associated with advanced disease and shortened survival. Plasma levels of thrombopoietin and interleukin-6 were significantly elevated in patients who had thrombocytosis as compared with those who did not. In mouse models, increased hepatic thrombopoietin synthesis in response to tumor-derived interleukin-6 was an underlying mechanism of paraneoplastic thrombocytosis. Tumorderived interleukin-6 and hepatic thrombopoietin were also linked to thrombocytosis in patients. Silencing thrombopoietin and interleukin-6 abrogated thrombocytosis in tumor-bearing mice. Anti–interleukin-6 antibody treatment significantly reduced platelet counts in tumor-bearing mice and in patients with epithelial ovarian cancer. In addition, neutralizing interleukin-6 significantly enhanced the therapeutic efficacy of paclitaxel in mouse models of epithelial ovarian cancer. The use of an antiplatelet antibody to halve platelet counts in tumor-bearing mice significantly reduced tumor growth and angiogenesis.</p> <p>Conclusions: These findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplastic thrombocytosis, which fuels tumor growth. We speculate that countering paraneoplastic thrombocytosis either directly or indirectly by targeting these cytokines may have therapeutic potential. </p&gt

Análisis arqueosismológico del conjunto arqueológico romano de Mulva- Munigua (Sevilla, España). Resultados preliminares

El conjunto arqueológico romano de Mulva-Munigua (Sevilla, España) presenta daños en las edificaciones que pueden ser interpretadas como resultado de la ocurrencia de un evento sísmico (Efectos Arqueológicos de los Terremotos: EAEs) a finales del siglo III A.D., fecha coincidente con el inicio del periodo de declive económico de este asentamiento romano. Para intentar establecer el posible origen sísmico de las deformaciones, se ha procedido al inventario y análisis de las estructuras deformadas presentes en el yacimiento. No obstante, algunas de estas deformaciones también se pueden interpretar como resultado de procesos gravitaciones asociados a la ladera Este de la colina sobre la que se sitúa parte del yacimiento. Las direcciones de máxima deformación (ey) obtenidas del análisis de EAEs indica dos direcciones preferentes de la deformación (o movimiento preferente del terreno): NNO-SSE y ENEOSO. Aunque los datos presentan una dispersión importante, se puede establecer que la orientación principal NNO-SSE es compatible con un evento sísmico situado en el borde norte del Valle del Guadalquivir. La orientación ENE-OSO podría relacionarse con un evento posterior, o más seguramente con procesos de ladera de carácter cosísmico o no.The Roman archaeological site of Mulva-Munigua (Sevilla, Spain) displays building damage features suggesting a seismic origin (Earthquake Archaeological Effects: EAEs). The proposed seismic event could be tentatively dated in the late 3rd century AD, coinciding with the beginning of the economic fall of the Roman Empire at Iberia. However, some of the recorded EAEs can be also interpreted as a result of intervening slope movements in the eastern hillslope of this roman site. The inventory and analysis of the proposed EAEs make possible to discern between seismic oriented damage and other causes. In spite of the data show a significant dispersion, their analysis result in two different orientations of maximum deformation (ey) or preferential ground movement: NNW-SSE and ENE-WSW. The main ey orientation (NNW-SSE) can be tentatively related to a seismic event occurred in the environs of the northern border of the Guadalquivir Depression. The secondary orientation (ENE-WSW) can be interpreted as a consequence of latter slope movements triggered (or not) by other ancient earthquakes

High platelet reactivity in patients with acute coronary syndromes undergoing percutaneous coronary intervention: Randomised controlled trial comparing prasugrel and clopidogrel

Background: Prasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e. poor responders, is limited. Objectives: To determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome (ACS). Patients: Patients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer, i.e. “poor responders” were randomised to prasugrel (60 mg loading and 10 mg maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose). The primary outcome measure was proportion of patients with platelet reactivity <40 AUC 4 hours after loading with study medication, and also at one hour (secondary outcome). 44 patients were enrolled and the study was terminated early as clopidogrel use decreased sharply due to introduction of newer P2Y12 inhibitors. Results: At 4 hours after study medication 100% of patients treated with prasugrel compared to 91% of those treated with clopidogrel had platelet reactivity <40 AUC (p = 0.49), while at 1 hour the proportions were 95% and 64% respectively (p = 0.02). Mean platelet reactivity at 4 and 1 hours after study medication in prasugrel and clopidogrel groups respectively were 12 versus 22 (p = 0.005) and 19 versus 34 (p = 0.01) respectively. Conclusions: Routine platelet function testing identifies patients with high residual platelet reactivity (“poor responders”) on clopidogrel. A strategy of prasugrel rather than clopidogrel reloading results in earlier and more sustained suppression of platelet reactivity. Future trials need to identify if this translates into clinical benefit

Dynamic and wear study of an extremely bidisperse magnetorheological fluid

Acceso a la versión publicada en Smart Mater. Struct. 24(12) 127001 (http://iopscience.iop.org/0964-1726/24/12/127001)"This is an author-created, un-copyedited version of an article accepted for publication/published in Smart Materials and Structures. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at http://dx.doi.org/10.1088/0964-1726/24/12/127001."In this work the friction and wear properties of five magnetorheologicalfluids (MRFs)with varying compositions are investigated. Considering that many of the proposed applications for these fluids involve lubricated contact between mobile metal –metal or polymer– metal parts, the relationship between MR response and wear behavior appears to be of fundamental importance. One of the fluids(MR#1)contains only the iron microparticles and base oil; the second and third ones(MR#2 and MR#3) contain an anti-wear additive as well. The fourth one(MR#4)is a well known commercial MRF. Finally, MR#5 is stabilized by dispersing the iron particles in a magnetite ferrofluid. The MR response of the latter fluid is better(higher yield stress and post-yield viscosity)than that of the others. More importantly, it remains(and even improves)after the wear test: the pressure applied in the four-ball apparatus produces a compaction of the magnetite layer around the iron microparticles. Additionally, the friction coefficient is larger, which seems paradoxical in principle, but can be explained by considering the stability of MR#5 in comparison to the other four MRs, which appear to undergo partial phase separation during the test. In fact, electron and optical microscope observations confirm a milder wear effect of MR#5, with almost complete absence of scars from the steel test spheres and homogeneous and shallow grooves on them. Comparatively, MR#2, MR#3 and, particularly, MR#1 produce a much more significant wear.MINECO Ramón y Cajal Programme (RYC-2014-16901)MINECO FIS 2013-07666-C3-1-RCEI Biotic BS27.2015Junta de Andalucía, PE2012-FQM-069