240 research outputs found
Predictive performance of parent-metabolite population pharmacokinetic models of (S)-ketamine in healthy volunteers
Purpose The recent repurposing of ketamine as treatment for pain and depression has increased the need for accurate population pharmacokinetic (PK) models to inform the design of new clinical trials. Therefore, the objectives of this study were to externally validate available PK models on (S)-(nor)ketamine concentrations with in-house data and to improve the best performing model when necessary. Methods Based on predefined criteria, five models were selected from literature. Data of two previously performed clinical trials on (S)-ketamine administration in healthy volunteers were available for validation. The predictive performances of the selected models were compared through visual predictive checks (VPCs) and calculation of the (root) mean (square) prediction errors (ME and RMSE). The available data was used to adapt the best performing model through alterations to the model structure and re-estimation of inter-individual variability (IIV). Results The model developed by Fanta et al. (Eur J Clin Pharmacol 71:441-447, 2015) performed best at predicting the (S)-ketamine concentration over time, but failed to capture the (S)-norketamine C-max correctly. Other models with similar population demographics and study designs had estimated relatively small distribution volumes of (S)-ketamine and thus overpredicted concentrations after start of infusion, most likely due to the influence of circulatory dynamics and sampling methodology. Model predictions were improved through a reduction in complexity of the (S)-(nor)ketamine model and re-estimation of IIV. Conclusion The modified model resulted in accurate predictions of both (S)-ketamine and (S)-norketamine and thereby provides a solid foundation for future simulation studies of (S)-(nor)ketamine PK in healthy volunteers after (S)-ketamine infusion.Stress-related psychiatric disorders across the life spa
Nonquasiparticle states in half-metallic ferromagnets
Anomalous magnetic and electronic properties of the half-metallic
ferromagnets (HMF) have been discussed. The general conception of the HMF
electronic structure which take into account the most important correlation
effects from electron-magnon interactions, in particular, the spin-polaron
effects, is presented. Special attention is paid to the so called
non-quasiparticle (NQP) or incoherent states which are present in the gap near
the Fermi level and can give considerable contributions to thermodynamic and
transport properties. Prospects of experimental observation of the NQP states
in core-level spectroscopy is discussed. Special features of transport
properties of the HMF which are connected with the absence of one-magnon
spin-flip scattering processes are investigated. The temperature and magnetic
field dependences of resistivity in various regimes are calculated. It is shown
that the NQP states can give a dominate contribution to the temperature
dependence of the impurity-induced resistivity and in the tunnel junction
conductivity. First principle calculations of the NQP-states for the prototype
half-metallic material NiMnSb within the local-density approximation plus
dynamical mean field theory (LDA+DMFT) are presented.Comment: 27 pages, 9 figures, Proceedings of Berlin/Wandlitz workshop 2004;
Local-Moment Ferromagnets. Unique Properties for Moder Applications, ed. M.
Donath, W.Nolting, Springer, Berlin, 200
Anisotropy in granular media: classical elasticity and directed force chain network
A general approach is presented for understanding the stress response
function in anisotropic granular layers in two dimensions. The formalism
accommodates both classical anisotropic elasticity theory and linear theories
of anisotropic directed force chain networks. Perhaps surprisingly, two-peak
response functions can occur even for classical, anisotropic elastic materials,
such as triangular networks of springs with different stiffnesses. In such
cases, the peak widths grow linearly with the height of the layer, contrary to
the diffusive spreading found in `stress-only' hyperbolic models. In principle,
directed force chain networks can exhibit the two-peak, diffusively spreading
response function of hyperbolic models, but all models in a particular class
studied here are found to be in the elliptic regime.Comment: 34 pages, 17 figures (eps), submitted to PRE, figures amended,
partially to compare better to recent exp. wor
Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events
The - oscillation frequency has been measured with a sample of
23 million \B\bar B pairs collected with the BABAR detector at the PEP-II
asymmetric B Factory at SLAC. In this sample, we select events in which both B
mesons decay semileptonically and use the charge of the leptons to identify the
flavor of each B meson. A simultaneous fit to the decay time difference
distributions for opposite- and same-sign dilepton events gives ps.Comment: 7 pages, 1 figure, submitted to Physical Review Letter
Evaluation of six empirical evapotranspiration equations - case study: Campos dos Goytacazes/RJ
A mind-brain-body dataset of MRI, EEG, cognition, emotion, and peripheral physiology in young and old adults
Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors
Background:Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens.Methods:In a Dutch cohort of 3121 5-year HL survivors treated between 1965 and 1995, subsite-specific CRC incidence was compared with general population rates. Treatment effects were quantified by Cox regression analyses.Results:After a median follow-up of 2
Níveis de feno de alfafa e forma física da ração no desempenho de cordeiros em creep feeding
The Earth: Plasma Sources, Losses, and Transport Processes
This paper reviews the state of knowledge concerning the source of magnetospheric plasma at Earth. Source of plasma, its acceleration and transport throughout the system, its consequences on system dynamics, and its loss are all discussed. Both observational and modeling advances since the last time this subject was covered in detail (Hultqvist et al., Magnetospheric Plasma Sources and Losses, 1999) are addressed
Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)
BACKGROUND:
Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control.
METHODS:
Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights.
FINDINGS:
5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease.
INTERPRETATION:
International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems
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