Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

<p>Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.</p> <p>Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.</p> <p>Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.</p&gt

Exclusive photoproduction of pi degrees up to large values of Mandelstam variables s, t, and u with CLAS

Exclusive photoproduction cross sections have been measured for the process $\gamma p \rightarrow p\pi^0(e^+e^-(\gamma))$ with the Dalitz decay final state using tagged photon energies in the range of $E_{\gamma} = 1.275-5.425$ GeV. The complete angular distribution of the final state $\pi^0$, for the entire photon energy range up to large values of $t$ and $u$, has been measured for the first time. The data obtained show that the cross section $d\sigma/dt$, at mid to large angles, decreases with energy as $s^{-6.89\pm 0.26}$. This is in agreement with the perturbative QCD quark counting rule prediction of $s^{-7}$. Paradoxically, the size of angular distribution of measured cross sections is greatly underestimated by the QCD based Generalized Parton Distribution mechanism at highest available invariant energy $s=11$ GeV$^2$. At the same time, the Regge exchange based models for $\pi^0$ photoproduction are more consistent with experimental data.Comment: 7 pages, 6 figure

A novel engineered VEGF blocker with an excellent pharmacokinetic profile and robust anti-tumor activity

BACKGROUND: Relatively poor penetration and retention in tumor tissue has been documented for large molecule drugs including therapeutic antibodies and recombinant immunoglobulin constant region (Fc)-fusion proteins due to their large size, positive charge, and strong target binding affinity. Therefore, when designing a large molecular drug candidate, smaller size, neutral charge, and optimal affinity should be considered. METHODS: We engineered a recombinant protein by molecular engineering the second domain of VEGFR1 and a few flanking residues fused with the Fc fragment of human IgG1, which we named HB-002.1. This recombinant protein was extensively characterized both in vitro and in vivo for its target-binding and target-blocking activities, pharmacokinetic profile, angiogenesis inhibition activity, and anti-tumor therapeutic efficacy. RESULTS: HB-002.1 has a molecular weight of ~80 kDa, isoelectric point of ~6.7, and an optimal target binding affinity ofdays, maximal concentration of 20.27 mug/ml, and area under the curve of 81.46 mug.days/ml. When tested in a transgenic zebrafish embryonic angiogenesis model, dramatic inhibition in angiogenesis was exhibited by a markedly reduced number of subintestinal vessels. When tested for anti-tumor efficacy, HB-002.1 was confirmed in two xenograft tumor models (A549 and Colo-205) to have a robust tumor killing activity, showing a percentage of inhibition over 90% at the dose of 20 mg/kg. Most promisingly, HB-002.1 showed a superior therapeutic efficacy compared to bevacizumab in the A549 xenograft model (tumor inhibition: 84.7% for HB-002.1 versus 67.6% for bevacizumab,

The climatic cyclicity in semiarid-arid central Asia over the past 500,000 years

Central Asia is currently a semiarid-arid region, dominated by the Westerlies. It is important to understand mechanisms of climate and precipitation changes here, as water availability in the region is crucial today and in the future. High-resolution, absolutely-dated oxygen isotope (delta(18)O) records of stalagmites from Kesang Cave characterize a dynamic precipitation history over most of the past 500,000 years. This record demonstrates, for the first time, that climate change in the region exhibits a processional rhythm with abrupt inceptions of low delta(18)O speleothem growth at times of high Northern Hemisphere summer insolation followed by gradual delta(18)O increases that track decreases of insolation. These observations and interpretations contrast with the interpretation of nearby, but higher elevation ice core records. The absolutely-dated cave delta(18)O shifts can be used to correlate the regional climate variability by providing chronological marks. Combined with other paleoclimate records, the Kesang observations suggest that possible incursions of Asian summer monsoon rainfall or related moisture into the Kesang site and/or adjacent areas during the high insolation times may play an important role in changing orbital-scale hydrology of the region. Based on our record, arid climate will prevail in this region for the next several millennia, providing that anthropogenic effects do not supersede natural processes.</p

Gamma-ray astronomy and cosmic-ray physics with ARGO-YBJ

The ARGO-YBJ detector, located 4300 m a.s.l. on the Tibet plateau, is a ground-based, full- coverage array of Resistive Plate Chambers (RPCs) covering a surface of 78×74 m2, surrounded by a guard ring of RPCs enclosing a total surface of about 11000 m2. ARGO-YBJ was designed to detect extensive air showers generated by cosmic rays and gamma rays with primary energy greater than few hundred GeV, in order to study the region of the cosmic-ray spectrum out of the reach of both satellite-based experiments and traditional ground-based arrays. The experiment has been running with its complete layout since November 2007, collecting over 2:5×1011 events. The main results obtained by ARGO-YBJ will be presented here, and specifically: the monitoring of astronomical gamma-ray sources, such as the Crab nebula and the MRK 421 AGN, the moon shadow, the medium-scale anisotropy map, the proton-proton inelastic cross section at center-of- mass energy between 70 and 500 GeV where no accelerator data are available

Gamma-ray astronomy with ARGO-YBJ

ARGO-YBJ is a full coverage air shower array located at the YangBaJing Cosmic Ray Laboratory (Tibet, P.R. China, 4300 m a.s.l., 606 g/cm2) recording data with a duty cycle ≥85% and an energy threshold of a few hundred GeV. In this paper the latest results in Gamma-Ray Astronomy are summarized