612 research outputs found
Differential fMet-Leu-Phe- and Platelet-activating Factor-induced Signaling Toward Ral Activation in Primary Human Neutrophils
We have measured the activation of the small GTPase
Ral in human neutrophils after stimulation with fMet-
Leu-Phe (fMLP), platelet activating factor (PAF), and
granulocyte macrophage-colony stimulating factor and
compared it with the activation of two other small
GTPases, Ras and Rap1. We found that fMLP and PAF,
but not granulocyte macrophage-colony stimulating factor,
induce Ral activation. All three stimuli induce the
activation of both Ras and Rap1. Utilizing specific inhibitors
we demonstrate that fMLP-induced Ral activation
is mediated by pertussis toxin-sensitive G-proteins and
partially by Src-like kinases, whereas fMLP-induced
Ras activation is independent of Src-like kinases. PAFinduced
Ral activation is mediated by pertussis toxininsensitive
proteins, Src-like kinases and phosphatidylinositol
3-kinase. Phosphatidylinositol 3-kinase is not
involved in PAF-induced Ras activation. The calcium
ionophore ionomycin activates Ral, but calcium depletion
partially inhibits fMLP- and PAF-induced Ral activation,
whereas Ras activation was not affected. In addition,
12-O-tetradecanoylphorbol-13-acetate-induced
activation of Ral is completely abolished by inhibitors of
protein kinase C, whereas 12-O-tetradecanoylphorbol-
13-acetate-induced Ras activation is largely insensitive.
We conclude that in neutrophils Ral activation is mediated
by multiple pathways, and that fMLP and PAF induce
Ral activation differently
Cost effectiveness of physiotherapy, manual therapy, and general practitioner care for neck pain: economic evaluation alongside a randomised controlled trial
OBJECTIVE: To evaluate the cost effectiveness of physiotherapy, manual therapy, and care by a general practitioner for patients with neck pain. DESIGN: Economic evaluation alongside a randomised controlled trial. SETTING: Primary care. PARTICIPANTS: 183 patients with neck pain for at least two weeks recruited by 42 general practitioners and randomly allocated to manual therapy (n=60, spinal mobilisation), physiotherapy (n=59, mainly exercise), or general practitioner care (n=64, counselling, education, and drugs). MAIN OUTCOME MEASURES: Clinical outcomes were perceived recovery, intensity of pain, functional disability, and quality of life. Direct and indirect costs were measured by means of cost diaries that were kept by patients for one year. Differences in mean costs between groups, cost effectiveness, and cost utility ratios were evaluated by applying non-parametric bootstrapping techniques. RESULTS: The manual therapy group showed a faster improvement than the physiotherapy group and the general practitioner care group up to 26 weeks, but differences were negligible by follow up at 52 weeks. The total costs of manual therapy (447 euro; 273 pounds sterling; 402 dollars) were around one third of the costs of physiotherapy (1297 euro) and general practitioner care (1379 euro). These differences were significant: P <0.01 for manual therapy versus physiotherapy and manual therapy versus general practitioner care and P=0.55 for general practitioner care versus physiotherapy. The cost effectiveness ratios and the cost utility ratios showed that manual therapy was less costly and more effective than physiotherapy or general practitioner care. CONCLUSIONS: Manual therapy (spinal mobilisation) is more effective and less costly for treating neck pain than physiotherapy or care by a general practitione
Cost-effectiveness of physiotherapy, manual therapy and general practioner care for neck pain: economic evaluation alongside a randomised controlled trial
Spin Interacting Fields and Heavy Baryon Chiral Perturbation Theory
We analyze the consistency of the Chiral Lagrangian approach to the
description of the spin 3/2 interacting theory. We argue that to lowest order
in the 1/m expansion, the formalism leads to the appropriated constraints and
the theory is free of the so called ``off shell" ambiguities.Comment: 12 pages, Late
Manual therapy, physical therapy, or continued care by the general practitioner for patients with neck pain - Long-term results from a pragmatic randomized clinical trial
OBJECTIVES: The authors' goals were to compare the effectiveness of manual therapy (MT; mainly spinal mobilization), physical therapy (PT; mainly exercise therapy), and continued care by the general practitioner (GP; analgesics, counseling and education) over a period of 1 year. METHODS: One hundred eighty-three patients suffering for at least 2 weeks from nonspecific neck pain were randomized to receive a 6-week treatment strategy of MT once a week, PT twice a week, or GP care once every 2 weeks. The primary outcome measures were perceived recovery, severity of physical dysfunctioning, pain intensity, and functional disability. RESULTS: The differences between groups considered over 1 year were statistically significant (repeated measurements analyses P <0.001 to P=0.02) for all outcomes but borderline for the Neck Disability Index (P=0.06). Higher improvement scores were observed for MT for all outcomes, followed by PT and GP care. The success rate, based on perceived recovery after 13 weeks, was 72% for MT, which was significantly higher than the success rate for continued GP care (42%, P=0.001) but not significantly higher compared with PT treatment (59%, P=0.16). The difference between PT and GP approached statistical significance (P=0.06). After 1 year the success rates were 75%, 63%, and 56%, respectively, and no longer significantly different. CONCLUSIONS: Short-term results (at 7 weeks) have shown that MT speeded recovery compared with GP care and, to a lesser extent, also compared with PT. In the long-term, GP treatment and PT caught up with MT, and differences between the three treatment groups decreased and lost statistical significance at the 13-week and 52-week follow-u
Stochastic processes with finite correlation time: modeling and application to the generalized Langevin equation
The kangaroo process (KP) is characterized by various forms of the covariance
and can serve as a useful model of random noises. We discuss properties of that
process for the exponential, stretched exponential and algebraic (power-law)
covariances. Then we apply the KP as a model of noise in the generalized
Langevin equation and simulate solutions by a Monte Carlo method. Some results
appear to be incompatible with requirements of the fluctuation-dissipation
theorem because probability distributions change when the process is inserted
into the equation. We demonstrate how one can construct a model of noise free
of that difficulty. This form of the KP is especially suitable for physical
applications.Comment: 22 pages (RevTeX) and 4 figure
MRI-Based Assessment of Brain Tumor Hypoxia:Correlation with Histology
Cerebral hypoxia significantly impacts the progression of brain tumors and their resistance to radiotherapy. This study employed streamlined quantitative blood-oxygen-level-dependent (sqBOLD) MRI to assess the oxygen extraction fraction (OEF)-a measure of how much oxygen is being extracted from vessels, with higher OEF values indicating hypoxia. Simultaneously, we utilized vessel size imaging (VSI) to evaluate microvascular dimensions and blood volume. A cohort of ten patients, divided between those with glioma and those with brain metastases, underwent a 3 Tesla MRI scan. We generated OEF, cerebral blood volume (CBV), and vessel size maps, which guided 3-4 targeted biopsies per patient. Subsequent histological analyses of these biopsies used hypoxia-inducible factor 1-alpha (HIF-1α) for hypoxia and CD31 for microvasculature assessment, followed by a correlation analysis between MRI and histological data. The results showed that while the sqBOLD model was generally applicable to brain tumors, it demonstrated discrepancies in some metastatic tumors, highlighting the need for model adjustments in these cases. The OEF, CBV, and vessel size maps provided insights into the tumor's hypoxic condition, showing intertumoral and intratumoral heterogeneity. A significant relationship between MRI-derived measurements and histological data was only evident in the vessel size measurements (r = 0.68, p < 0.001).</p
MRI-Based Assessment of Brain Tumor Hypoxia:Correlation with Histology
Cerebral hypoxia significantly impacts the progression of brain tumors and their resistance to radiotherapy. This study employed streamlined quantitative blood-oxygen-level-dependent (sqBOLD) MRI to assess the oxygen extraction fraction (OEF)—a measure of how much oxygen is being extracted from vessels, with higher OEF values indicating hypoxia. Simultaneously, we utilized vessel size imaging (VSI) to evaluate microvascular dimensions and blood volume. A cohort of ten patients, divided between those with glioma and those with brain metastases, underwent a 3 Tesla MRI scan. We generated OEF, cerebral blood volume (CBV), and vessel size maps, which guided 3–4 targeted biopsies per patient. Subsequent histological analyses of these biopsies used hypoxia-inducible factor 1-alpha (HIF-1α) for hypoxia and CD31 for microvasculature assessment, followed by a correlation analysis between MRI and histological data. The results showed that while the sqBOLD model was generally applicable to brain tumors, it demonstrated discrepancies in some metastatic tumors, highlighting the need for model adjustments in these cases. The OEF, CBV, and vessel size maps provided insights into the tumor’s hypoxic condition, showing intertumoral and intratumoral heterogeneity. A significant relationship between MRI-derived measurements and histological data was only evident in the vessel size measurements (r = 0.68, p < 0.001).</p
Gross tumour volume delineation in anal cancer on T2-weighted and diffusion-weighted MRI - Reproducibility between radiologists and radiation oncologists and impact of reader experience level and DWI image quality
Abstract Purpose To assess how gross tumour volume (GTV) delineation in anal cancer is affected by interobserver variations between radiologists and radiation oncologists, expertise level, and use of T2-weighted MRI (T2W-MRI) vs. diffusion-weighted imaging (DWI), and to explore effects of DWI quality. Methods and materials We retrospectively analyzed the MRIs (T2W-MRI and b800-DWI) of 25 anal cancer patients. Four readers (Senior and Junior Radiologist; Senior and Junior Radiation Oncologist) independently delineated GTVs, first on T2W-MRI only and then on DWI (with reference to T2W-MRI). Maximum Tumour Diameter (MTD) was calculated from each GTV. Mean GTVs/MTDs were compared between readers and between T2W-MRI vs. DWI. Interobserver agreement was calculated as Intraclass Correlation Coefficient (ICC), Dice Similarity Coefficient (DSC) and Hausdorff Distance (HD). DWI image quality was assessed using a 5-point artefact scale. Results Interobserver agreement between radiologists vs. radiation oncologists and between junior vs. senior readers was good–excellent, with similar agreement for T2W-MRI and DWI (e.g. ICCs 0.72–0.94 for T2W-MRI and 0.68–0.89 for DWI). There was a trend towards smaller GTVs on DWI, but only for the radiologists (P = 0.03–0.07). Moderate-severe DWI-artefacts were observed in 11/25 (44%) cases. Agreement tended to be lower in these cases. Conclusion Overall interobserver agreement for anal cancer GTV delineation on MRI is good for both radiologists and radiation oncologists, regardless of experience level. Use of DWI did not improve agreement. DWI artefacts affecting GTV delineation occurred in almost half of the patients, which may severely limit the use of DWI for radiotherapy planning if no steps are undertaken to avoid them
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