Mechanism-based model characterizing bidirectional interaction between PEGylated liposomal CKD-602 (S-CKD602) and monocytes in cancer patients

S-CKD602 is a PEGylated liposomal formulation of CKD-602, a potent topoisomerase I inhibitor. The objective of this study was to characterize the bidirectional pharmacokinetic-pharmacodynamic (PK-PD) interaction between S-CKD602 and monocytes. Plasma concentrations of encapsulated CKD-602 and monocytes counts from 45 patients with solid tumors were collected following intravenous administration of S-CKD602 in the phase I study. The PK-PD models were developed and fit simultaneously to the PK-PD data, using NONMEM®. The monocytopenia after administration of S-CKD602 was described by direct toxicity to monocytes in a mechanism-based model, and by direct toxicity to progenitor cells in bone marrow in a myelosuppression-based model. The nonlinear PK disposition of S-CKD602 was described by linear degradation and irreversible binding to monocytes in the mechanism-based model, and Michaelis-Menten kinetics in the myelosuppression-based model. The mechanism-based PK-PD model characterized the nonlinear PK disposition, and the bidirectional PK-PD interaction between S-CKD602 and monocytes. © 2012 Cárdenas et al, publisher and licensee Dove Medical Press Ltd

High rate of lymphoma among a UK cohort of adolescents with vertically acquired HIV-1 infection transitioning to adult care in the era of antiretroviral therapy

Among an inner London UK cohort of 147 adolescents transitioning from paediatric into adult care between 2007 and 2015, a new diagnosis of lymphoma was made in five patients; incidence rate = 0.425/100 person-years (95% confidence interval = 0.424–0.426). Previously described risk factors, including low nadir CD4+ cell count and ongoing HIV-1 viraemia, appeared to be important. These data suggest that careful surveillance and a low threshold for investigating relevant symptoms continue to be essential for such patients

Convergence of chiral effective field theory

We formulate the expansion for the mass of the nucleon as a function of pion mass within chiral perturbation theory using a number of different ultra-violet regularisation schemes; including dimensional regularisation and various finite-ranged regulators. Leading and next-to-leading order non-analytic contributions are included through the standard one-loop Feynman graphs. In addition to the physical nucleon mass, the expansion is constrained by recent, extremely accurate, lattice QCD data obtained with two flavors of dynamical quarks. The extent to which different regulators can describe the chiral expansion is examined, while varying the range of quark mass over which the expansions are matched. Renormalised chiral expansion parameters are recovered from each regularisation prescription and compared. We find that the finite-range regulators produce consistent, model-independent results over a wide range of quark mass sufficient to solve the chiral extrapolation problem in lattice QCD.Comment: 13 pages, 13 figures; To appear in Progress in Particle and Nuclear Physics; presented at Erice School on Quarks in Hadrons and Nuclei, September 200

A Radical Approach to Ebola: Saving Humans and Other Animals

As the usual regulatory framework did not fit well during the last Ebola outbreak, innovative thinking still needed. In the absence of an outbreak, randomised controlled trials of clinical efficacy in humans cannot be done, while during an outbreak such trials will continue to face significant practical, philosophical, and ethical challenges. This article argues that researchers should also test the safety and effectiveness of novel vaccines in wild apes by employing a pluralistic approach to evidence. There are three reasons to test vaccines in wild populations of apes: i) protect apes; ii) reduce Ebola transmission from wild animals to humans; and iii) accelerate vaccine development and licensing for humans. Data obtained from studies of vaccines among wild apes and chimpanzees may even be considered sufficient for licensing new vaccines for humans. This strategy will serve to benefit both wild apes and humans

Low-energy couplings of QCD from current correlators near the chiral limit

We investigate a new numerical procedure to compute fermionic correlation functions at very small quark masses. Large statistical fluctuations, due to the presence of local ``bumps'' in the wave functions associated with the low-lying eigenmodes of the Dirac operator, are reduced by an exact low-mode averaging. To demonstrate the feasibility of the technique, we compute the two-point correlator of the left-handed vector current with Neuberger fermions in the quenched approximation, for lattices with a linear extent of L~1.5 fm, a lattice spacing a~0.09 fm, and quark masses down to the epsilon-regime. By matching the results with the corresponding (quenched) chiral perturbation theory expressions, an estimate of (quenched) low-energy constants can be obtained. We find agreement between the quenched values of F extrapolated from the p-regime and extracted in the epsilon-regime.Comment: 20 pages, 5 figure

Exploring variations in childhood stunting in Nigeria using league table, control chart and spatial analysis

Background: Stunting, linear growth retardation is the best measure of child health inequalities as it captures multiple dimensions of children’s health, development and environment where they live. The developmental priorities and socially acceptable health norms and practices in various regions and states within Nigeria remains disaggregated and with this, comes the challenge of being able to ascertain which of the regions and states identifies with either high or low childhood stunting to further investigate the risk factors and make recommendations for action oriented policy decisions. Methods: We used data from the birth histories included in the 2008 Nigeria Demographic and Health Survey (DHS) to estimate childhood stunting. Stunting was defined as height for age below minus two standard deviations from the median height for age of the standard World Health Organization reference population. We plotted control charts of the proportion of childhood stunting for the 37 states (including federal capital, Abuja) in Nigeria. The Local Indicators of Spatial Association (LISA) were used as a measure of the overall clustering and is assessed by a test of a null hypothesis. Results: Childhood stunting is high in Nigeria with an average of about 39%. The percentage of children with stunting ranged from 11.5% in Anambra state to as high as 60% in Kebbi State. Ranking of states with respect to childhood stunting is as follows: Anambra and Lagos states had the least numbers with 11.5% and 16.8% respectively while Yobe, Zamfara, Katsina, Plateau and Kebbi had the highest (with more than 50% of their underfives having stunted growth). Conclusions: Childhood stunting is high in Nigeria and varied significantly across the states. The northern states have a higher proportion than the southern states. There is an urgent need for studies to explore factors that may be responsible for these special cause variations in childhood stunting in Nigeria

Macro-Climatic Distribution Limits Show Both Niche Expansion and Niche Specialization among C4 Panicoids

Grasses are ancestrally tropical understory species whose current dominance in warm open habitats is linked to the evolution of C4 photosynthesis. C4 grasses maintain high rates of photosynthesis in warm and water stressed environments, and the syndrome is considered to induce niche shifts into these habitats while adaptation to cold ones may be compromised. Global biogeographic analyses of C4 grasses have, however, concentrated on diversity patterns, while paying little attention to distributional limits. Using phylogenetic contrast analyses, we compared macro-climatic distribution limits among ~1300 grasses from the subfamily Panicoideae, which includes 4/5 of the known photosynthetic transitions in grasses. We explored whether evolution of C4 photosynthesis correlates with niche expansions, niche changes, or stasis at subfamily level and within the two tribes Paniceae and Paspaleae. We compared the climatic extremes of growing season temperatures, aridity, and mean temperatures of the coldest months. We found support for all the known biogeographic distribution patterns of C4 species, these patterns were, however, formed both by niche expansion and niche changes. The only ubiquitous response to a change in the photosynthetic pathway within Panicoideae was a niche expansion of the C4 species into regions with higher growing season temperatures, but without a withdrawal from the inherited climate niche. Other patterns varied among the tribes, as macro-climatic niche evolution in the American tribe Paspaleae differed from the pattern supported in the globally distributed tribe Paniceae and at family level.Fil: Aagesen, Lone. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Botánica Darwinion. Academia Nacional de Ciencias Exactas, Físicas y Naturales. Instituto de Botánica Darwinion; ArgentinaFil: Biganzoli, Fernando. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Métodos Cuantitativos y Sistemas de Información; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bena, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Botánica Darwinion. Academia Nacional de Ciencias Exactas, Físicas y Naturales. Instituto de Botánica Darwinion; ArgentinaFil: Godoy Bürki, Ana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Botánica Darwinion. Academia Nacional de Ciencias Exactas, Físicas y Naturales. Instituto de Botánica Darwinion; ArgentinaFil: Reinheimer, Renata. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; ArgentinaFil: Zuloaga, Fernando Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Botánica Darwinion. Academia Nacional de Ciencias Exactas, Físicas y Naturales. Instituto de Botánica Darwinion; Argentin

The psychological-type profile of clergywomen in ordained local ministry in the Church of England : pioneers or custodians?

This study employs psychological-type theory to compare the psychological profile of 144 clergywomen serving in ordained local ministry in the Church of England alongside the established profile of 237 professional mobile clergywomen serving in the Church of England published by Francis, Craig, Whinney, Tilley, and Slater. The data found no significant differences between these two groups of clergywomen in terms of orientations (introversion and extraversion) or in terms of the judging process (thinking and feeling). In terms of the perceiving process, there was a significantly higher proportion of sensing types among those serving in ordained local ministry (70% compared with 35%). In terms of the attitudes, there was a significantly higher proportion of judging types among those serving in ordained local ministry (83% compared with 65%). The combined sensing judging (SJ) temperament accounted for 65% of the clergywomen serving in ordained local ministry, compared with 29% of the clergywomen serving in professional mobile ministry in the earlier study. It is argued that the SJ temperament characterises a custodian style of ministry

The ρ(1S,2S)\rho(1S,2S), ψ(1S,2S)\psi(1S,2S), Υ(1S,2S)\Upsilon(1S,2S) and ψt(1S,2S)\psi_t(1S,2S) mesons in a double pole QCD Sum Rule

We use the method of double pole QCD sum rule which is basically a fit with two exponentials of the correlation function, where we can extract the masses and decay constants of mesons as a function of the Borel mass. We apply this method to study the mesons: $\rho(1S,2S)$, $\psi(1S,2S)$, $\Upsilon(1S,2S)$ and $\psi_t(1S,2S)$. We also present predictions for the toponiuns masses $\psi_t(1S,2S)$ of m(1S)=357 GeV and m(2S)=374 GeV.Comment: 14 pages, 11 figures in Braz J Phys (2016