437 research outputs found
Interactions of cholera toxin with isolated hepatocytes. Effects of low pH, chloroquine and monensin on toxin internalization, processing and action
A phase I pharmacokinetic and safety study of cabazitaxel in adult cancer patients with normal and impaired renal function
Limited data are available on cabazitaxel pharmacokinetics in patients with renal impairment. This open-label, multicenter study assessed cabazitaxel in patients with advanced solid tumors and normal or impaired renal function.
Cohorts A (normal renal function: creatinine clearance [CrCL]Â >80Â mL/min/1.73Â m), B (moderate renal impairment: CrCL 30 to <50Â mL/min/1.73Â m) and C (severe impairment: CrCLÂ <30Â mL/min/1.73Â m(2)) received cabazitaxel 25Â mg/m (A, B) or 20Â mg/m(2) (C, could be escalated to 25Â mg/m), once every 3Â weeks. Pharmacokinetic parameters and cabazitaxel unbound fraction (F) were assessed using linear regression and mixed models. Geometric mean (GM) and GM ratios (GMRs) were determined using mean CrCL intervals (moderate and severe renal impairment: 40 and 15Â mL/min/1.73Â m) versus a control (90Â mL/min/1.73Â m).
Overall, 25 patients received cabazitaxel (median cycles: 3 [range 1-20]; Cohort A: 5 [2-13]; Cohort B: 3 [1-15]; and Cohort C: 5 [1-20]), of which 24 were eligible for pharmacokinetic analysis (eight in each cohort). For moderate and severe renal impairment versus normal renal function, GMR estimates were: clearance normalized to body surface area (CL/BSA) 0.95 (90% CI 0.80-1.13) and 0.89 (0.61-1.32); area under the curve normalized to dose (AUC/dose) 1.06 (0.88-1.27) and 1.14 (0.76-1.71); and F U 0.99 (0.94-1.04) and 0.97 (0.87-1.09), respectively. Estimated slopes of linear regression of log parameters versus log CrCL (renal impairment) were: CL/BSA 0.06 (-0.15 to 0.28); AUC/dose -0.07 (-0.30 to 0.16); and F U 0.02 (-0.05 to 0.08). Cabazitaxel safety profile was consistent with previous reports.
Renal impairment had no clinically meaningful effect on cabazitaxel pharmacokinetics.This study was supported by Sanofi. Javier Garcia-Corbacho acknowledges clinical fellowship support from SEOM. Experimental Cancer Medicine Centre (ECMC) and NIHR Biomedical Research Centre (BRC) funding is also acknowledged for the Cambridge Cancer Centre
Pharmacokinetic (Pk) Activity of Cabazitaxel (Cbz) in Patients (Pts) with Renal Impairment (Ri)
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Meson-induced correlations of nucleons in nuclear Compton scattering
The non-resonant (seagull) contribution to the nuclear Compton amplitude at
low energies is strongly influenced by nucleon correlations arising from meson
exchange. We study this problem in a modified Fermi gas model, where nuclear
correlation functions are obtained with the help of perturbation theory. The
dependence of the mesonic seagull amplitude on the nuclear radius is
investigated and the influence of a realistic nuclear density on this amplitude
is dicussed. We found that different form factors appear for the static part
(proportional to the enhancement constant ) of the mesonic seagull
amplitude and for the parts, which contain the contribution from
electromagnetic polarizabilities.Comment: 15 pages, Latex, epsf.sty, 9 eps figures
Articulating practice through the interview to the double
The paper aims to realise the critical potential of the practice lens by contributing to the
development of a coherent set of methodologies for investigating work and
organisational activity. It does so by introducing and critically assessing the "interview
to the double" as a method to articulate and represent practice.
After briefly illustrating its history and usage, the paper analyses in depth the setting
generated by this unusual interview method. It argues that the nature of the encounter
produces narratives that are often morally connoted and idealised in character. As a
consequence the method is especially useful to capture the going concerns which orient
the conduct of the members and the normative and moral dimension of practice. The
paper also shows that because it mimics familiar instruction-giving discursive practices,
the method constitutes an effective textual device to convey this moral and normative
dimension in a way which remains faithful to its situated and contingent nature of
practice
Towards a codification of practical knowledge
International audienceAs practical knowledge seems to have a central place in organisational issues, we focus on possibilities to study and formalize it. From an unusual theoretical perspective, we view practical knowledge as embodied knowing which only is only manifest through action in a particular situation. Although this knowledge is largely implicit, we try to make what is 'articulable' explicit. After highlighting the stakes involved in the codification of practices, we review the ontological and epistemological assumptions underlying the method developed. It is founded on participant observation, a video recording of a situated subjective perspective and an ex post interview using this perspective to aid an actor to make part of his/her practical knowledge explicit. We present its implementation within research on polar expeditions in order to understand how an experienced actor deals with risks. In conclusion, we point out (1) the importance of this kind of data in knowledge management, (2) some lines of further research
A apropriação de gĂȘneros textuais pelo professor: em direção ao desenvolvimento pessoal e Ă evolução do "mĂ©tier"
The Spin-Dependent Structure Functions of Nuclei in the Meson-Nucleon Theory
A theoretical approach to the investigation of spin-dependent structure
functions in deep inelastic scattering of polarized leptons off polarized
nuclei, based on the effective meson-nucleon theory and operator product
expansion method, is proposed and applied to deuteron and . The explicit
forms of the moments of the deuteron and spin-dependent structure
functions are found and numerical estimates of the influence of nuclear
structure effects are presented.Comment: 42 pages revtex, 7 postscript figures available from above e-mail
upon request. Perugia preprint DFUPG 92/9
Clinical Symptoms in Fibromyalgia Are Better Associated to Lipid Peroxidation Levels in Blood Mononuclear Cells Rather than in Plasma
This is an open-access article distributed under the terms of the Creative Commons Attribution License.[Background] We examined lipid peroxidation (LPO) in blood mononuclear cells (BMCs) and plasma, as a marker of oxidative damage, and its association to clinical symptoms in Fibromyalgia (FM) patients.
[Methods]: We conducted a caseâcontrol and correlational study comparing 65 patients and 45 healthy controls. Clinical parameters were evaluated using the Fibromyalgia Impact Questionnaire (FIQ), visual analogues scales (VAS), and the Beck Depression Inventory (BDI). Oxidative stress was determined by measuring LPO in BMCs and plasma. [Results]:
We found increased LPO levels in BMCs and plasma from FM patients as compared to normal control (P<0.001). A significant correlation between LPO in BMCs and clinical parameters was observed (r = 0.584, P<0.001 for VAS; r = 0.823, P<0.001 for FIQ total score; and r = 0.875, P<0.01 for depression in the BDI). We also found a positive correlation between LPO in plasma and clinical symptoms (r = 0.452, P<0.001 for VAS; r = 0.578, P<0.001 for FIQ total score; and r = 0.579, P<0.001 for depression in the BDI). Partial correlation analysis controlling for age and BMI, and sex, showed that both LPO in cells and plasma were independently associated to clinical symptoms. However, LPO in cells, but not LPO in plasma, was independently associated to clinical symptoms when controlling for depression (BDI scores). [Discussion]: The results of this study suggest a role for oxidative stress in the pathophysiology of fibromyalgia and that LPO in BMCs rather than LPO in plasma is better associated to clinical symptoms in FM.This work was supported by Spanish FIS PI080500 grant, and FIS EC08/00076 grant, Ministerio de Sanidad, Spain, and FederaciĂłn Andaluza de Fibromialgia y Fatiga CrĂłnica (ALBA AndalucĂa). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe
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