135 research outputs found
Intervention thresholds for osteoporosis in men and women: A study based on data from Sweden
The aim of this study was to determine the threshold of fracture probability at which interventions became cost-effective in men and women, based on data from Sweden. We modeled the effects of a treatment costing 200-500/year). Data on costs and risks were from Sweden. Costs included direct costs, but excluded indirect costs due to morbidity. A threshold for cost-effectiveness of approximately 500 per year; 35% efficacy) treatment in women was cost-effective with a 10-year hip fracture probability that ranged from 1.2% at the age of 50 years to 7.4% at the age of 80 years. Similar results were observed in men except that the threshold for cost-effectiveness was higher at younger ages than in women (2.0 vs 1.2%, respectively, at the age of 50 years). Intervention thresholds were sensitive to the assumed effectiveness and intervention cost. The exclusion of osteoporotic fractures other than hip fracture significantly increased the cost-effectiveness ratio because of the substantial morbidity from such other fractures, particularly at younger ages. We conclude that the inclusion of all osteoporotic fractures has a marked effect on intervention thresholds, that these vary with age, and that available treatments can be targeted cost-effectively to individuals at moderately increased fracture risk
Thermodynamic perturbation theory for dipolar superparamagnets
Thermodynamic perturbation theory is employed to derive analytical
expressions for the equilibrium linear susceptibility and specific heat of
lattices of anisotropic classical spins weakly coupled by the dipole-dipole
interaction. The calculation is carried out to the second order in the coupling
constant over the temperature, while the single-spin anisotropy is treated
exactly. The temperature range of applicability of the results is, for weak
anisotropy (A/kT << 1), similar to that of ordinary high-temperature
expansions, but for moderately and strongly anisotropic spins (A/kT > 1) it can
extend down to the temperatures where the superparamagnetic blocking takes
place (A/kT \sim 25), provided only the interaction strength is weak enough.
Besides, taking exactly the anisotropy into account, the results describe as
particular cases the effects of the interactions on isotropic (A = 0) as well
as strongly anisotropic (A \to \infty) systems (discrete orientation model and
plane rotators).Comment: 15 pages, 3 figure
Treatment with subcutaneous and transdermal fentanyl: Results from a population pharmacokinetic study in cancer patients
Purpose: Transdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we studied the pharmacokinetics of subcutaneous and transdermal fentanyl. Furthermore, we evaluated rotations from the subcutaneous to the transdermal route. Methods: Fifty-two patients treated with subcutaneous and/or transdermal fentanyl for moderate to severe cancer-related pain participated. A population pharmacokinetic model was developed and evaluated using non-linear mixed-effects modelling. For rotations from subcutaneous to transdermal fentanyl, a 1:1 dose conversion ratio was used while the subcutaneous infusion was continued for 12 h (with a 50 % tapering after 6 h). A 6-h scheme with 50 % tapering after 3 h was simulated using the final model. Results: A one-compartment model with first-order elimination and separate first-order absorption processes for each route adequately described the data. The estimated apparent clearance of fentanyl was 49.6 L/h; the absorption rate constant for subcutaneous and transdermal fentanyl was 0.0358 and 0.0135 h-1, respectively. Moderate to large inter-individual and inter-occasion variability was found. Around rotation from subcutaneous to transdermal fentanyl, measured and simulated plasma fentanyl concentrations rose and increasing side effects were observed. Conclusions: We describe the pharmacokinetics of subcutaneous and transdermal fentanyl in one patient cohort and report several findings that are relevant for clinical practice. Further research is warranted to study the optimal scheme for rotations from the subcutaneous to the transdermal route
A Prospective Population Pharmacokinetic Study on Morphine Metabolism in Cancer Patients
Background: Oral and subcutaneous morphine is widely used for the treatment of cancer-related pain; however, solid pharmacokinetic data on this practice are lacking. Furthermore, it is largely unknown which factors contribute to the variability in clearances of morphine and its metabolites and whether morphine clearance is related to treatment outcome. Methods: Blood samples from 49 cancer patients treated with oral and/or subcutaneous morphine were prospectively collected and were used to develop a population pharmacokinetic model for morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). The influence of age, gender, renal function and several polymorphisms possibly related to the pharmacokinetics of the three compounds was investigated. In addition, the relation between treatment failure and morphine and metabolite clearances was explored. Results: A one-compartment model including an extensive first-pass effect adequately described the data of morphine and its metabolites. Estimated mean area under the plasma concentration–time curve (AUC) ratios following oral versus subcutaneous administration were: M3G/morphine 29.7:1 vs. 11.1:1; M6G/morphine 5.26:1 vs. 1.95:1; and M3G/M6G 5.65:1 vs. 5.70:1. Renal function was significantly correlated with clearance of the metabolites, which increased 0.602 L/h per every 10 mL/min/1.73 m2 increase of estimated glomerular filtr
Quantitative predictions on auxin-induced polar distribution of PIN proteins during vein formation in leaves
The dynamic patterning of the plant hormone auxin and its efflux facilitator
the PIN protein are the key regulator for the spatial and temporal organization
of plant development. In particular auxin induces the polar localization of its
own efflux facilitator. Due to this positive feedback auxin flow is directed
and patterns of auxin and PIN arise. During the earliest stage of vein
initiation in leaves auxin accumulates in a single cell in a rim of epidermal
cells from which it flows into the ground meristem tissue of the leaf blade.
There the localized auxin supply yields the successive polarization of PIN
distribution along a strand of cells. We model the auxin and PIN dynamics
within cells with a minimal canalization model. Solving the model analytically
we uncover an excitable polarization front that triggers a polar distribution
of PIN proteins in cells. As polarization fronts may extend to opposing
directions from their initiation site we suggest a possible resolution to the
puzzling occurrence of bipolar cells, such we offer an explanation for the
development of closed, looped veins. Employing non-linear analysis we identify
the role of the contributing microscopic processes during polarization.
Furthermore, we deduce quantitative predictions on polarization fronts
establishing a route to determine the up to now largely unknown kinetic rates
of auxin and PIN dynamics.Comment: 9 pages, 4 figures, supplemental information included, accepted for
publication in Eur. Phys. J.
Interpreting Quantum Particles as Conceptual Entities
We elaborate an interpretation of quantum physics founded on the hypothesis
that quantum particles are conceptual entities playing the role of
communication vehicles between material entities composed of ordinary matter
which function as memory structures for these quantum particles. We show in
which way this new interpretation gives rise to a natural explanation for the
quantum effects of interference and entanglement by analyzing how interference
and entanglement emerge for the case of human concepts. We put forward a scheme
to derive a metric based on similarity as a predecessor for the structure of
'space, time, momentum, energy' and 'quantum particles interacting with
ordinary matter' underlying standard quantum physics, within the new
interpretation, and making use of aspects of traditional quantum axiomatics.
More specifically, we analyze how the effect of non-locality arises as a
consequence of the confrontation of such an emerging metric type of structure
and the remaining presence of the basic conceptual structure on the fundamental
level, with the potential of being revealed in specific situations.Comment: 19 pages, 1 figur
Search for Doubly-Charged Higgs Boson Production at HERA
A search for the single production of doubly-charged Higgs bosons H^{\pm \pm}
in ep collisions is presented. The signal is searched for via the Higgs decays
into a high mass pair of same charge leptons, one of them being an electron.
The analysis uses up to 118 pb^{-1} of ep data collected by the H1 experiment
at HERA. No evidence for doubly-charged Higgs production is observed and mass
dependent upper limits are derived on the Yukawa couplings h_{el} of the Higgs
boson to an electron-lepton pair. Assuming that the doubly-charged Higgs only
decays into an electron and a muon via a coupling of electromagnetic strength
h_{e \mu} = \sqrt{4 \pi \alpha_{em}} = 0.3, a lower limit of 141 GeV on the
H^{\pm\pm} mass is obtained at the 95% confidence level. For a doubly-charged
Higgs decaying only into an electron and a tau and a coupling h_{e\tau} = 0.3,
masses below 112 GeV are ruled out.Comment: 15 pages, 3 figures, 1 tabl
Low Q^2 Jet Production at HERA and Virtual Photon Structure
The transition between photoproduction and deep-inelastic scattering is
investigated in jet production at the HERA ep collider, using data collected by
the H1 experiment. Measurements of the differential inclusive jet
cross-sections dsigep/dEt* and dsigmep/deta*, where Et* and eta* are the
transverse energy and the pseudorapidity of the jets in the virtual
photon-proton centre of mass frame, are presented for 0 < Q2 < 49 GeV2 and 0.3
< y < 0.6. The interpretation of the results in terms of the structure of the
virtual photon is discussed. The data are best described by QCD calculations
which include a partonic structure of the virtual photon that evolves with Q2.Comment: 20 pages, 5 Figure
Hadron Production in Diffractive Deep-Inelastic Scattering
Characteristics of hadron production in diffractive deep-inelastic
positron-proton scattering are studied using data collected in 1994 by the H1
experiment at HERA. The following distributions are measured in the
centre-of-mass frame of the photon dissociation system: the hadronic energy
flow, the Feynman-x (x_F) variable for charged particles, the squared
transverse momentum of charged particles (p_T^{*2}), and the mean p_T^{*2} as a
function of x_F. These distributions are compared with results in the gamma^* p
centre-of-mass frame from inclusive deep-inelastic scattering in the
fixed-target experiment EMC, and also with the predictions of several Monte
Carlo calculations. The data are consistent with a picture in which the
partonic structure of the diffractive exchange is dominated at low Q^2 by hard
gluons.Comment: 16 pages, 6 figures, submitted to Phys. Lett.
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