The International Reference Ionosphere (IRI), a joint project of URSI and COSPAR, is the de facto international standard for the climatological specification of ionospheric parameters and as such it ...is currently undergoing registration as Technical Specification (TS) of the International Standardization Organization (ISO). IRI by charter and design is an empirical model based on a wide range of ground and space data. It describes monthly averages of ionospheric densities and temperatures in the altitude range 50–1500
km in the non-auroral ionosphere. Since its inception in 1969 the IRI model has been steadily improved with newer data and with better mathematical descriptions of global and temporal variation patterns. A large number of independent studies have validated the IRI model in comparisons with direct and indirect ionospheric measurements not used in the model development. A comparison with IRI is often one of the first science tasks by an ionospheric satellite or rocket team.
This paper describes the latest version of the IRI model, IRI-2007, explaining the most important changes that are being introduced with this version. These include: (1) two new options for the topside electron density, (2) a new model for the topside ion composition, (3) the first-time inclusion of a model for the spread F occurrence probability, (4) a NeuralNet model for auroral E-region electron densities, (5) a model for the plasmaspheric electron temperature, and (6) the latest International Geomagnetic Reference Field (IGRF) model for the computation of magnetic coordinates including their changes due to the secular variation of the magnetic field.
The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program was initiated by the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD). It examined ...potential treatment targets for inflammatory bowel disease (IBD) to be used for a "treat-to-target" clinical management strategy using an evidence-based expert consensus process.
A Steering Committee of 28 IBD specialists developed recommendations based on a systematic literature review and expert opinion. Consensus was gained if ≥75% of participants scored the recommendation as 7-10 on a 10-point rating scale (where 10=agree completely).
The group agreed upon 12 recommendations for ulcerative colitis (UC) and Crohn's disease (CD). The agreed target for UC was clinical/patient-reported outcome (PRO) remission (defined as resolution of rectal bleeding and diarrhea/altered bowel habit) and endoscopic remission (defined as a Mayo endoscopic subscore of 0-1). Histological remission was considered as an adjunctive goal. Clinical/PRO remission was also agreed upon as a target for CD and defined as resolution of abdominal pain and diarrhea/altered bowel habit; and endoscopic remission, defined as resolution of ulceration at ileocolonoscopy, or resolution of findings of inflammation on cross-sectional imaging in patients who cannot be adequately assessed with ileocolonoscopy. Biomarker remission (normal C-reactive protein (CRP) and calprotectin) was considered as an adjunctive target.
Evidence- and consensus-based recommendations for selecting the goals for treat-to-target strategies in patients with IBD are made available. Prospective studies are needed to determine how these targets will change disease course and patients' quality of life.
Global Ionospheric Radio Observatory (GIRO) Reinisch, Bodo W.; Galkin, Ivan A.
Earth, planets and space,
01/2011, Letnik:
63, Številka:
4
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
Digisonde ionospheric sounders installed at 80+ locations in the world have gradually evolved their generally independent existence into a Global Ionospheric Radio Observatory (GIRO) portal. Today ...GIRO provides public access to 30+ million records of ionospheric measurements collected at 64 locations, of which 42 provide realtime feeds, publishing their measurement data within several minutes from their completion. GIRO databases holding ionogram and Doppler skymap records of high-frequency ionospheric soundings have registered connections from 123 organizations in 33 countries. Easy access to the global state of the ionospheric plasma distribution given in accurate and fine detail by the ionosonde measurements has inspired a number of studies of the ionospheric response to space weather events. Availability of GIRO data with minimal latency allows for the assimilation of the ionogram-derived data in real-time models such as the real-time extension planned for the International Reference Ionosphere.
We present a newly developed empirical model of the plasma density in the plasmasphere. It is based on more than 700 density profiles along field lines derived from active sounding measurements made ...by the radio plasma imager on IMAGE between June 2000 and July 2005. The measurements cover all magnetic local times and vary from L = 1.6 to L = 4 spatially, with every case manually confirmed to be within the plasmasphere by studying the corresponding dynamic spectrogram. The resulting model depends not only on L‐shell but also on magnetic latitude and can be applied to specify the electron densities in the plasmasphere between 2000 km altitude and the plasmapause (the plasmapause location itself is not included in this model). It consists of two parts: the equatorial density, which falls off exponentially as a function of L‐shell; and the field‐aligned dependence on magnetic latitude and L‐shell (in the form of invariant magnetic latitude). The fluctuations of density appear to be greater than what could be explained by a possible dependence on magnetic local time or season, and the dependence on geomagnetic activity is weak and cannot be discerned. The solar cycle effect is not included because the database covers only a fraction of a solar cycle. The performance of the model is evaluated by comparison to four previously developed plasmaspheric models and is further tested against the in situ passive IMAGE RPI measurements of the upper hybrid resonance frequency. While the equatorial densities of different models are mostly within the statistical uncertainties (especially at distances greater than L = 3), the clear latitudinal dependence of the RPI model presents an improvement over previous models. The model shows that the field‐aligned density distribution can be treated neither as constant nor as a simple diffusive equilibrium distribution profile. This electron density model combined with an assumed model of the ion composition can be used to estimate the time for an Alfven wave to propagate from one hemisphere to the other, to determine the plasma frequencies along a field line, and to calculate the raypaths for high frequency waves propagating in the plasmasphere.
Key Points
Improved empirical model of the Earth's plasmasphere
Realistic description of the field‐aligned electron density distribution
Possible applications in studies of the inner magnetosphere and wave propagation
Aliment Pharmacol Ther 2011; 34: 113–124
Summary
Background There is no international agreement on scoring systems used to measure disease activity in ulcerative colitis, nor is there a validated ...definition for disease remission.
Aim To review the principles and components for defining remission in ulcerative colitis and propose a definition that will help improve patient outcomes.
Methods A review of current standards of remission from the perspective of clinical trials, guidelines, clinical practice and patients was conducted by the authors. Selected literature focused on the components of a definition of remission, the utility of a definition and treatment strategies, based on current definitions.
Results Different definitions of remission affect the assessment of outcome and make it difficult to compare trials. In the clinic, endoscopy is rarely used to confirm remission, because mucosal healing has only recently begun to be related to the duration of subsequent remission in a way that will affect clinical practice. Histopathology may be the ultimate arbiter of mucosal healing. There is no agreement on the definition of remission in current guidelines. Patient‐defined remission may predict endoscopic remission, but has yet to be shown to predict duration of remission.
Conclusions A standard based on clinical symptoms and endoscopy is proposed. Histopathology is a third dimension of remission that may have prognostic value. The definition of remission should help predict long‐term outcome. The expectations of patients and their physicians need to be raised, as the goal of treatment of active ulcerative colitis should be to induce remission.
Summary
Background
Vedolizumab, an anti‐α4β7 integrin monoclonal antibody (mAb), is indicated for treating patients with moderately to severely active ulcerative colitis (UC) and Crohn's disease ...(CD). As higher therapeutic mAb concentrations have been associated with greater efficacy in inflammatory bowel disease, understanding determinants of vedolizumab clearance may help to optimise dosing.
Aims
To characterise vedolizumab pharmacokinetics in patients with UC and CD, to identify clinically relevant determinants of vedolizumab clearance, and to describe the pharmacokinetic–pharmacodynamic relationship using population modelling.
Methods
Data from a phase 1 healthy volunteer study, a phase 2 UC study, and 3 phase 3 UC/CD studies were included. Population pharmacokinetic analysis for repeated measures was conducted using nonlinear mixed effects modelling. Results from the base model, developed using extensive phase 1 and 2 data, were used to develop the full covariate model, which was fit to sparse phase 3 data.
Results
Vedolizumab pharmacokinetics was described by a 2‐compartment model with parallel linear and nonlinear elimination. Using reference covariate values, linear elimination half‐life of vedolizumab was 25.5 days; linear clearance (CLL) was 0.159 L/day for UC and 0.155 L/day for CD; central compartment volume of distribution (Vc) was 3.19 L; and peripheral compartment volume of distribution was 1.66 L. Interindividual variabilities (%CV) were 35% for CLL and 19% for Vc; residual variance was 24%. Only extreme albumin and body weight values were identified as potential clinically important predictors of CLL.
Conclusions
Population pharmacokinetic parameters were similar in patients with moderately to severely active UC and CD. This analysis supports use of vedolizumab fixed dosing in these patients. Clinicaltrials.gov Identifiers: NCT01177228; NCT00783718 (GEMINI 1); NCT00783692 (GEMINI 2); NCT01224171 (GEMINI 3).
Aliment Pharmacol Ther 2011; 33: 857–869
Summary
Background Crohn’s disease is a progressive condition, with most patients developing a penetrating or stricturing complication over time. A decade ...ago, treatment goals consisted of immediate symptomatic control. The introduction of anti‐tumour necrosis factor (anti‐TNF) therapies, however, has changed the way patients with Crohn’s disease are treated. Over 10 years of clinical data and experience have demonstrated these therapies to be highly effective in Crohn’s disease.
Aim To provide clinicians guidance on optimising treatment with anti‐TNF therapies in Crohn’s disease by introducing an evidence‐ and personal opinion‐based treatment algorithm using infliximab initial anti‐TNF therapy.
Methods Scientific literature was reviewed using MEDLINE to evaluate data on clinical trials with infliximab in luminal and fistulising Crohn’s disease.
Results The data from several landmark infliximab trials have changed clinical practice and led to a readjustment of treatment goals in Crohn’s disease, allowing patients to achieve more than just symptomatic relief including sustained steroid‐free remission. Infliximab induces complete mucosal healing and reduces the rates of hospitalisation and surgery. Based on disease‐related risk factors, a treatment algorithm for infliximab is delineated in favour of a rapid step‐up approach in patients at high risk for a disabling course of disease.
Conclusion Adopting the suggested treatment algorithm for infliximab into clinical routine is aimed to optimise outcomes for patients with Crohn’s disease.
We treat whistler-mode radiation from a dipole antenna in a cold magnetized plasma based on the Fresnel zone construction theory. Radiated waves from the antenna with different propagation directions ...interfere in space. Regions of enhanced waves are formed when the interference is predominantly constructive at the observing point. The coherently enhanced wave propagates at the group velocity. If the antenna is perpendicular to the background magnetic field, the regions of strong waves form two back-to-back Fresnel zones that are parabolic-shaped cones along the background magnetic field from the antenna. The power within each cone drops with distance at a rate of <inline-formula> <tex-math notation="LaTeX">1/r </tex-math></inline-formula> much more slowly than the <inline-formula> <tex-math notation="LaTeX">1/r^{2} </tex-math></inline-formula> thinning of a spherical wave as in vacuum. The total radiation can be approximately derived by the total energy flux integrated over the Fresnel zone. The derived radiation resistance is much greater than that in vacuum. It is proportional to frequency as <inline-formula> <tex-math notation="LaTeX">1/f^{2} </tex-math></inline-formula> and proportional to the antenna length as <inline-formula> <tex-math notation="LaTeX">d^{2} </tex-math></inline-formula>. To radiate more power, a longer antenna is preferred, a result that is opposite to some previous theoretical studies.
Aliment Pharmacol Ther 2011; 34: 1–10
Summary
Background The addition of antitumour necrosis factor‐α (TNF‐α) agents to the therapeutic armamentarium against Crohn’s disease has been a revolution in ...its management. However, approximately 25 to 40% of patients who initially benefit from anti‐TNF‐α treatment develop intolerable adverse events or loose their response during maintenance therapy.
Aim To summarise the current knowledge on the mechanisms underlying loss of response in these patients and the therapeutic strategies available to counteract this clinical challenge.
Method A literature search using PubMed, MedLine and Embase databases has been performed.
Results Anti‐infliximab antibodies formation and autoantibodies (ANA, anti‐DNA and other autoantibodies) have been associated with loss of response. Individual differences in drug metabolism may contribute to loss of response. Smoking may be a risk factor for loss of response. Dose escalation, reduction of infusion intervals and switch to other anti‐TNF‐α agents are effective as rescue strategies.
Conclusions Loss of response appears to result from different causes not fully established by now. Optimization of therapies, or switch to other anti‐TNF‐α, are currently the best studied strategies in case of loss of response, and can be successful in 40–60% of patients who lose response.
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