Showing papers by "Université libre de Bruxelles published in 2004"
TL;DR: Cetuximab has clinically significant activity when given alone or in combination with irinotecan in patients with ir inotecans-refractory colorectal cancer.
Abstract: background The epidermal growth factor receptor (EGFR), which participates in signaling pathways that are deregulated in cancer cells, commonly appears on colorectal-cancer cells. Cetuximab is a monoclonal antibody that specifically blocks the EGFR. We compared the efficacy of cetuximab in combination with irinotecan with that of cetuximab alone in metastatic colorectal cancer that was refractory to treatment with irinotecan. methods We randomly assigned 329 patients whose disease had progressed during or within three months after treatment with an irinotecan-based regimen to receive either cetuximab and irinotecan (at the same dose and schedule as in a prestudy regimen [218 patients]) or cetuximab monotherapy (111 patients). In cases of disease progression, the addition of irinotecan to cetuximab monotherapy was permitted. The patients were evaluated radiologically for tumor response and were also evaluated for the time to tumor progression, survival, and side effects of treatment. results The rate of response in the combination-therapy group was significantly higher than that in the monotherapy group (22.9 percent [95 percent confidence interval, 17.5 to 29.1 percent] vs. 10.8 percent [95 percent confidence interval, 5.7 to 18.1 percent], P=0.007). The median time to progression was significantly greater in the combination-therapy group (4.1 vs. 1.5 months, P<0.001 by the log-rank test). The median survival time was 8.6 months in the combination-therapy group and 6.9 months in the monotherapy group (P=0.48). Toxic effects were more frequent in the combinationtherapy group, but their severity and incidence were similar to those that would be expected with irinotecan alone. conclusions Cetuximab has clinically significant activity when given alone or in combination with irinotecan in patients with irinotecan-refractory colorectal cancer.
4,625 citations
TL;DR: It is proved that replacing the usual quadratic regularizing penalties by weighted 𝓁p‐penalized penalties on the coefficients of such expansions, with 1 ≤ p ≤ 2, still regularizes the problem.
Abstract: We consider linear inverse problems where the solution is assumed to have a sparse expansion on an arbitrary preassigned orthonormal basis. We prove that replacing the usual quadratic regularizing penalties by weighted p-penalties on the coefficients of such expansions, with 1 ≤ p ≤ 2, still regularizes the problem. Use of such p-penalized problems with p < 2 is often advocated when one expects the underlying ideal noiseless solution to have a sparse expansion with respect to the basis under consideration. To compute the corresponding regularized solutions, we analyze an iterative algorithm that amounts to a Landweber iteration with thresholding (or nonlinear shrinkage) applied at each iteration step. We prove that this algorithm converges in norm. © 2004 Wiley Periodicals, Inc.
4,339 citations
TL;DR: In this study, 12 young, healthy, normal-weight men exhibited reductions in the satiety hormone leptin, increases in the hunger hormone ghrelin, and increases in hunger after 2 nights of only 4 hours of sleep compared with after two nights of 10 hours ofSleep, suggesting inadequate sleep seems to influence the hormones that regulate satiety and hunger.
Abstract: Sleep-deprived healthy persons experience increased hunger. They also have increased blood levels of leptin and decreased levels of ghrelin (hormones that regulate satiety and hunger). These hormon...
2,178 citations
TL;DR: A psychometrically well-justified measure of work-related stress (ERI) grounded in sociological theory is available for comparative socioepidemiologic investigations in advanced societies within and beyond Europe.
1,921 citations
TL;DR: It is proposed to quantify SGS by an ‘Sp’ statistic primarily dependent upon the rate of decrease of pairwise kinship coefficients between individuals with the logarithm of the distance in two dimensions, and shown how the approach presented can be extended to assess (i) the level of biparental inbreeding, and (ii) the kurtosis of the gene dispersal distribution.
Abstract: Many empirical studies have assessed fine-scale spatial genetic structure (SGS), i.e. the nonrandom spatial distribution of genotypes, within plant populations using genetic markers and spatial autocorrelation techniques. These studies mostly provided qualitative descriptions of SGS, rendering quantitative comparisons among studies difficult. The theory of isolation by distance can predict the pattern of SGS under limited gene dispersal, suggesting new approaches, based on the relationship between pairwise relatedness coefficients and the spatial distance between individuals, to quantify SGS and infer gene dispersal parameters. Here we review the theory underlying such methods and discuss issues about their application to plant populations, such as the choice of the relatedness statistics, the sampling scheme to adopt, the procedure to test SGS, and the interpretation of spatial autocorrelograms. We propose to quantify SGS by an ‘ Sp ’ statistic primarily dependent upon the rate of decrease of pairwise kinship coefficients between individuals with the logarithm of the distance in two dimensions. Under certain conditions, this statistic estimates the reciprocal of the neighbourhood size. Reanalysing data from, mostly, published studies, the Sp statistic was assessed for 47 plant species. It was found to be significantly related to the mating system (higher in selfing species) and to the life form (higher in herbs than trees), as well as to the population density (higher under low density). We discuss the necessity for comparing SGS with direct estimates of gene dispersal distances, and show how the approach presented can be extended to assess (i) the level of biparental inbreeding, and (ii) the kurtosis of the gene dispersal distribution.
1,154 citations
TL;DR: Sleep modulates a major component of the neuroendocrine control of appetite, and the effects of sleep duration on leptin were quantitatively associated with alterations of the cortisol and TSH profiles and were accompanied by an elevation of postbreakfast homeostasis model assessment values.
Abstract: Sleep plays an important role in energy homeostasis. The present study tests the hypothesis that circulating levels of leptin, a hormone that signals energy balance to the brain, are influenced by sleep duration. We also analyzed associations between leptin and sympathovagal balance, cortisol, TSH, glucose, and insulin under different bedtime conditions. Twenty-four-hour hormonal and glucose profiles were sampled at frequent intervals, and sympathovagal balance was estimated from heart rate variability in 11 subjects studied after 6 d of 4-h bedtimes (mean +/- sem of sleep duration during last 2 d: 3 h and 49 +/- 2 min) and after 6 d of 12-h bedtimes (sleep: 9 h and 03 +/- 15 min). A study with 8-h bedtimes was performed 1 yr later (sleep: 6 h and 52 +/- 10 min). Caloric intake and activity levels were carefully controlled in all studies. Mean levels, maximal levels, and rhythm amplitude of leptin were decreased (-19%, -26%, and -20%, respectively) during sleep restriction compared with sleep extension. The decrease in leptin levels was concomitant with an elevation of sympathovagal balance. The effects of sleep duration on leptin were quantitatively associated with alterations of the cortisol and TSH profiles and were accompanied by an elevation of postbreakfast homeostasis model assessment values. Measures of perceived stress were not increased during sleep restriction. During the study with 8-h bedtimes, hormonal and metabolic parameters were intermediate between those observed with 4-h and 12-h bedtimes. In conclusion, sleep modulates a major component of the neuroendocrine control of appetite.
907 citations
TL;DR: It is concluded that BCC lines are likely to reflect the features of cancer cells in vivo, and the importance of oestrogen receptor-alpha and Her-2/neu as classifiers for cell lines and tumours is underlined.
Abstract: The number of available breast cancer cell (BCC) lines is small, and only a very few of them have been extensively studied. Whether they are representative of the tumours from which they originated remains a matter of debate. Whether their diversity mirrors the well-known inter-tumoural heterogeneity is another essential question. While numerous similarities have long been found between cell lines and tumours, recent technical advances, including the use of micro-arrays and comparative genetic analysis, have brought new data to the discussion. This paper presents most of the BCC lines that have been described in some detail to date. It evaluates the accuracy of the few of them widely used (MCF-7, T-47D, BT-474, SK-BR-3, MDA-MB-231, Hs578T) as tumour models. It is concluded that BCC lines are likely to reflect, to a large extent, the features of cancer cells in vivo. The importance of oestrogen receptor-alpha (gene ESR1) and Her-2/neu (ERBB2) as classifiers for cell lines and tumours is underlined. The recourse to a larger set of cell lines is suggested since the exact origin of some of the widely used lines remains ambiguous. Investigations on additional specific lines are expected to improve our knowledge of BCC and of the dialogue that these maintain with their surrounding normal cells in vivo.
807 citations
TL;DR: Here a protocol for a high-fidelity transfer of an independently prepared quantum state of light onto an atomic quantum state based on atomic ensembles is proposed and experimentally demonstrated.
Abstract: The information carrier of today's communications, a weak pulse of light, is an intrinsically quantum object. As a consequence, complete information about the pulse cannot be perfectly recorded in a classical memory, even in principle. In the field of quantum information, this has led to the long-standing challenge of how to achieve a high-fidelity transfer of an independently prepared quantum state of light onto an atomic quantum state1,2,3,4. Here we propose and experimentally demonstrate a protocol for such a quantum memory based on atomic ensembles. Recording of an externally provided quantum state of light onto the atomic quantum memory is achieved with 70 per cent fidelity, significantly higher than the limit for classical recording. Quantum storage of light is achieved in three steps: first, interaction of the input pulse and an entangling field with spin-polarized caesium atoms; second, subsequent measurement of the transmitted light; and third, feedback onto the atoms using a radio-frequency magnetic pulse conditioned on the measurement result. The density of recorded states is 33 per cent higher than the best classical recording of light onto atoms, with a quantum memory lifetime of up to 4 milliseconds.
729 citations
TL;DR: In this paper, the basic conceptual framework of a new space-time theory with application to high energy particle physics is outlined, both achievements and limitations are discussed with direct reference to the mass spectrum problem.
Abstract: The essay outlines the basic conceptual framework of a new space–time theory with application to high energy particle physics. Both achievements and limitations are discussed with direct reference to the mass spectrum problem.
650 citations
TL;DR: The Ninth Catalogue of Spectroscopic Binary Orbits (http://sb9.astro.ulb.ac.be) as discussed by the authors is a collection of spectroscopic binary orbits carried out over the past 35 years.
Abstract: The Ninth Catalogue of Spectroscopic Binary Orbits (http://sb9.astro.ulb.ac.be) continues the series of compilations of spectroscopic orbits carried out over the past 35 years by Batten and collaborators. As of 2004 May 1st, the new Catalogue holds orbits for 2386 systems. Some essential differences between this catalogue and its predecessors are outlined and three straightforward applications are presented: (1) completeness assessment: period distribution of SB1s and SB2s; (2) shortest periods across the H-R diagram; (3) period-eccentricity relation.
574 citations
TL;DR: It is concluded that apoptosis is the main mode of FFA- and cytokine-induced beta-cell death but the mechanisms involved are different, suggesting that FFAs trigger an endoplasmic reticulum (ER) stress response through an NF-kappaB- and nitric oxide-independent mechanism.
Abstract: Apoptosis is probably the main form of beta-cell death in both type 1 diabetes mellitus (T1DM) and T2DM. In T1DM, cytokines contribute to beta-cell destruction through nuclear factor-kappaB (NF-kappaB) activation. Previous studies suggested that in T2DM high glucose and free fatty acids (FFAs) are beta-cell toxic also via NF-kappaB activation. The aims of this study were to clarify whether common mechanisms are involved in FFA- and cytokine-induced beta-cell apoptosis and determine whether TNFalpha, an adipocyte-derived cytokine, potentiates FFA toxicity through enhanced NF-kappaB activation. Apoptosis was induced in insulinoma (INS)-1E cells, rat islets, and fluorescence-activated cell sorting-purified beta-cells by oleate, palmitate, and/or cytokines (IL-1beta, interferon-gamma, TNFalpha). Palmitate and IL-1beta induced a similar percentage of apoptosis in INS-1E cells, whereas oleate was less toxic. TNFalpha did not potentiate FFA toxicity in primary beta-cells. The NF-kappaB-dependent genes inducible nitric oxide synthase and monocyte chemoattractant protein-1 were induced by IL-1beta but not by FFAs. Cytokines activated NF-kappaB in INS-1E and beta-cells, but FFAs did not. Moreover, FFAs did not enhance NF-kappaB activation by TNFalpha. Palmitate and oleate induced C/EBP homologous protein, activating transcription factor-4, and immunoglobulin heavy chain binding protein mRNAs, X-box binding protein-1 alternative splicing, and activation of the activating transcription factor-6 promoter in INS-1E cells, suggesting that FFAs trigger an endoplasmic reticulum (ER) stress response. We conclude that apoptosis is the main mode of FFA- and cytokine-induced beta-cell death but the mechanisms involved are different. Whereas cytokines induce NF-kappaB activation and ER stress (secondary to nitric oxide formation), FFAs activate an ER stress response via an NF-kappaB- and nitric oxide-independent mechanism. Our results argue against a unifying hypothesis for the mechanisms of beta-cell death in T1DM and T2DM.
Max Planck Society1, Yerevan Physics Institute2, Durham University3, Centre national de la recherche scientifique4, University of Hamburg5, Collège de France6, Université libre de Bruxelles7, Humboldt University of Berlin8, University of Montpellier9, Tata Institute of Fundamental Research10, École Polytechnique11, Dublin Institute for Advanced Studies12, DSM13, Joseph Fourier University14, North-West University15, Washington University in St. Louis16, Iowa State University17, Ruhr University Bochum18, University of Sheffield19, Charles University in Prague20, University of Namibia21
TL;DR: A TeV γ-ray image of the SNR shows the spatially resolved remnant has a shell morphology similar to that seen in X-rays, which demonstrates that very-high-energy particles are accelerated there, consistent with current ideas of particle acceleration in young SNR shocks.
Abstract: A significant fraction of the energy density of the interstellar medium is in the form of high-energy charged particles (cosmic rays)1. The origin of these particles remains uncertain. Although it is generally accepted that the only sources capable of supplying the energy required to accelerate the bulk of Galactic cosmic rays are supernova explosions, and even though the mechanism of particle acceleration in expanding supernova remnant (SNR) shocks is thought to be well understood theoretically2,3, unequivocal evidence for the production of high-energy particles in supernova shells has proven remarkably hard to find. Here we report on observations of the SNR RX J1713.7 - 3946 (G347.3 - 0.5), which was discovered by ROSAT4 in the X-ray spectrum and later claimed as a source of high-energy γ-rays5,6 of TeV energies (1 TeV = 1012 eV). We present a TeV γ-ray image of the SNR: the spatially resolved remnant has a shell morphology similar to that seen in X-rays, which demonstrates that very-high-energy particles are accelerated there. The energy spectrum indicates efficient acceleration of charged particles to energies beyond 100 TeV, consistent with current ideas of particle acceleration in young SNR shocks.
TL;DR: Symptoms in hereditary pancreatitis start in younger patients and endpoints take longer to be reached compared with other forms of chronic pancreatitis but the cumulative levels of exocrine and endocrine failure are much higher.
TL;DR: In this article, the long-term impact of various sources of knowledge (R&D performed by the business sector, the public sector and foreign firms) on multifactor productivity growth of 16 countries from 1980 to 1998 was presented.
Abstract: This paper presents estimates of the long-term impact of various sources of knowledge (R&D performed by the business sector, the public sector and foreign firms) on multifactor productivity growth of 16 countries from 1980 to 1998. The main results show that the three sources of knowledge are significant determinants of long-term productivity growth. Further evidence suggests that several factors determine the extent to which each source of knowledge contributes to productivity growth. These factors are the absorptive capability, the origin of funding, the socioeconomic objectives of government support, and the type of public institutions that perform R&D.
TL;DR: The causative mutations in AOA2 are identified in 15 families, which allows this entity to be clinically defined by onset between 10 and 22 years, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia and elevated alpha-fetoprotein.
Abstract: Ataxia-ocular apraxia 2 (AOA2) was recently identified as a new autosomal recessive ataxia. We have now identified causative mutations in 15 families, which allows us to clinically define this entity by onset between 10 and 22 years, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia and elevated alpha-fetoprotein (AFP). Ten of the fifteen mutations cause premature termination of a large DEAxQ-box helicase, the human ortholog of yeast Sen1p, involved in RNA maturation and termination.
TL;DR: The panoramic view of glucocorticoid actions on the immune system provides an interesting model for characterizing important biological pathways of immunosuppression, and could represent an adjuvant treatment to cell therapy in autoimmune diseases.
Abstract: Glucocorticoids have been used for over 50 years in the treatment of inflammatory and autoimmune diseases and in preventing graft rejection. Today, knowledge of their molecular, cellular, and pharmacological properties allows a better understanding of glucocorticoid-mediated immunosuppression. Glucocorticoids exert both negative and positive effects with a dynamic and bi-directional spectrum of activities on various limbs and components of the immune response. They modulate genes involved in the priming of the innate immune response, while their actions on the adaptive immune response are to suppress cellular (Th1) immunity and promote humoral (Th2) immunity. Interestingly, glucocorticoids can also induce tolerance to specific antigens by influencing dendritic cell maturation and function and promoting the development of regulatory high IL-10-producing T cells. The ex vivo therapeutic use of glucocorticoids could therefore represent an adjuvant treatment to cell therapy in autoimmune diseases, avoiding the long-term deleterious adverse effects of glucocorticoids. Thus, the panoramic view of glucocorticoid actions on the immune system provides an interesting model for characterizing important biological pathways of immunosuppression.
TL;DR: A surprisingly simple framework for the random generation of combinatorial configurations based on what the authors call Boltzmann models is proposed, which can be implemented easily, be analysed mathematically with great precision, and, when suitably tuned, tend to be very efficient in practice.
Abstract: This article proposes a surprisingly simple framework for the random generation of combinatorial configurations based on what we call Boltzmann models. The idea is to perform random generation of possibly complex structured objects by placing an appropriate measure spread over the whole of a combinatorial class – an object receives a probability essentially proportional to an exponential of its size. As demonstrated here, the resulting algorithms based on real-arithmetic operations often operate in linear time. They can be implemented easily, be analysed mathematically with great precision, and, when suitably tuned, tend to be very efficient in practice.
TL;DR: A new robotic concept called swarm-bot is introduced in which the collective interaction exploited by the swarm intelligence mechanism goes beyond the control layer and is extended to the physical level, which implies the addition of new mechanical functionalities on the single robot, together with new electronics and software to manage it.
Abstract: The swarm intelligence paradigm has proven to have very interesting properties such as robustness, flexibility and ability to solve complex problems exploiting parallelism and self-organization. Several robotics implementations of this paradigm confirm that these properties can be exploited for the control of a population of physically independent mobile robots.
The work presented here introduces a new robotic concept called swarm-bot in which the collective interaction exploited by the swarm intelligence mechanism goes beyond the control layer and is extended to the physical level. This implies the addition of new mechanical functionalities on the single robot, together with new electronics and software to manage it. These new functionalities, even if not directly related to mobility and navigation, allow to address complex mobile robotics problems, such as extreme all-terrain exploration.
The work shows also how this new concept is investigated using a simulation tool (swarmbot3d) specifically developed for quickly designing and evaluating new control algorithms. Experimental work shows how the simulated detailed representation of one s-bot has been calibrated to match the behaviour of the real robot.
TL;DR: This paper introduces a self-assembling and self-organizing artifact, called a swarm-bot, composed of a swarm of s-bots, mobile robots with the ability to connect to and to disconnect from each other.
Abstract: In this paper, we introduce a self-assembling and self-organizing artifact, called a swarm-bot, composed of a swarm of s-bots, mobile robots with the ability to connect to and to disconnect from each other. We discuss the challenges involved in controlling a swarm-bot and address the problem of synthesizing controllers for the swarm-bot using artificial evolution. Specifically, we study aggregation and coordinated motion of the swarm-bot using a physics-based simulation of the system. Experiments, using a simplified simulation model of the s-bots, show that evolution can discover simple but effective controllers for both the aggregation and the coordinated motion of the swarm-bot. Analysis of the evolved controllers shows that they have properties of scalability, that is, they continue to be effective for larger group sizes, and of generality, that is, they produce similar behaviors for configurations different from those they were originally evolved for. The portability of the evolved controllers to real s-bots is tested using a detailed simulation model which has been validated against the real s-bots in a companion paper in this same special issue.
University of Mainz1, University of Delaware2, University of California, Berkeley3, University of Wuppertal4, University of Maryland, College Park5, Université libre de Bruxelles6, University of Kansas7, Stockholm University8, Uppsala University9, Lawrence Berkeley National Laboratory10, University of Mons11, University of Wisconsin-Madison12, Pennsylvania State University13, Vrije Universiteit Brussel14, George Mason University15, Southern University and A&M College16, Clark Atlanta University17, Chiba University18, Imperial College London19, University of Wisconsin–River Falls20, Simón Bolívar University21, Utrecht University22
TL;DR: In this paper, a Monte Carlo study of the sensitivity of the planned IceCube detector to predicted fluxes of muon neutrinos at TeV to PeV energies is presented.
TL;DR: In this article, the role of IL-10 in host defense against Streptococcus pneumoniae after recovery from influenza infection was evaluated in a mouse model to study post-influenza pneumococcal pneumonia.
Abstract: Secondary pneumococcal pneumonia is a serious complication during and shortly after influenza infection. We established a mouse model to study postinfluenza pneumococcal pneumonia and evaluated the role of IL-10 in host defense against Streptococcus pneumoniae after recovery from influenza infection. C57BL/6 mice were intranasally inoculated with 10 median tissue culture infective doses of influenza A (A/PR/8/34) or PBS (control) on day 0. By day 14 mice had regained their normal body weight and had cleared influenza virus from the lungs, as determined by real-time quantitative PCR. On day 14 after viral infection, mice received 10(4) CFU of S. pneumoniae (serotype 3) intranasally. Mice recovered from influenza infection were highly susceptible to subsequent pneumococcal pneumonia, as reflected by a 100% lethality on day 3 after bacterial infection, whereas control mice showed 17% lethality on day 3 and 83% lethality on day 6 after pneumococcal infection. Furthermore, 1000-fold higher bacterial counts at 48 h after infection with S. pneumoniae and, particularly, 50-fold higher pulmonary levels of IL-10 were observed in influenza-recovered mice than in control mice. Treatment with an anti-IL-10 mAb 1 h before bacterial inoculation resulted in reduced bacterial outgrowth and markedly reduced lethality during secondary bacterial pneumonia compared with those in IgG1 control mice. In conclusion, mild self-limiting influenza A infection renders normal immunocompetent mice highly susceptible to pneumococcal pneumonia. This increased susceptibility to secondary bacterial pneumonia is at least in part caused by excessive IL-10 production and reduced neutrophil function in the lungs.
TL;DR: The mechanism by which binding of the hormones results in activation is proposed to involve switching of the ectodomain from a tethered inverse agonist to a full agonist of the serpentine, rhodopsin-like region of the receptor.
TL;DR: In this article, a new measurement of the 14N(p,γ) 15O capture cross section at Ep=140 to 400 keV using the 400 kV LUNA accelerator facility at the Laboratori Nazionali del Gran Sasso (LNGS) was reported.
TL;DR: Long-term followup of patients from the ELNT confirms that, in lupus nephritis, a remission-inducing regimen of low-dose IV CYC followed by AZA achieves clinical results comparable with those obtained with a high-dose regimen.
Abstract: OBJECTIVE: In the Euro-Lupus Nephritis Trial (ELNT), 90 patients with lupus nephritis were randomly assigned to a high-dose intravenous cyclophosphamide (IV CYC) regimen (6 monthly pulses and 2 quarterly pulses with escalating doses) or a low-dose IV CYC regimen (6 pulses of 500 mg given at intervals of 2 weeks), each of which was followed by azathioprine (AZA). After a median followup of 41 months, a difference in efficacy between the 2 regimens was not observed. The present analysis was undertaken to extend the followup and to identify prognostic factors. METHODS: Renal function was prospectively assessed quarterly in all 90 patients except 5 who were lost to followup. Survival curves were derived using the Kaplan-Meier method. RESULTS: After a median followup of 73 months, there was no significant difference in the cumulative probability of end-stage renal disease or doubling of the serum creatinine level in patients who received the low-dose IV CYC regimen versus those who received the high-dose regimen. At long-term followup, 18 patients (8 receiving low-dose and 10 receiving high-dose treatment) had developed permanent renal impairment and were classified as having poor long-term renal outcome. We demonstrated by multivariate analysis that early response to therapy at 6 months (defined as a decrease in serum creatinine level and proteinuria <1 g/24 hours) was the best predictor of good long-term renal outcome. CONCLUSION: Long-term followup of patients from the ELNT confirms that, in lupus nephritis, a remission-inducing regimen of low-dose IV CYC followed by AZA achieves clinical results comparable with those obtained with a high-dose regimen. Early response to therapy is predictive of good long-term renal outcome.
TL;DR: It is shown that the perceptual system is able to adaptively recalibrate itself to audio-visual temporal asynchronies and the point of subjective simultaneity was shifted in the direction of the exposure lag, indicative of recalibration.
TL;DR: Oral ibandronate 50 mg is an effective, well-tolerated and convenient treatment for the prevention of skeletal complications of metastatic bone disease and has been evaluated in phase III clinical trials of patients with bone metastases from breast cancer.
Abstract: Although intravenous (i.v.) bisphosphonates are the standard of care for metastatic bone disease, they are less than ideal for many patients due to infusion-related adverse events (AEs), an increased risk of renal toxicity and the inconvenience of regular hospital visits. The use of oral bisphosphonate therapy is limited by concerns over efficacy and gastrointestinal (GI) side effects. There remains a clinical need for an oral bisphosphonate that offers equivalent efficacy to i.v. bisphosphonates, good tolerability and dosing convenience. Oral ibandronate, a highly potent, third-generation aminobisphosphonate, has been evaluated in phase III clinical trials of patients with bone metastases from breast cancer. In two pooled phase III studies, patients with breast cancer and bone metastases were randomised to receive oral ibandronate 50 mg (n=287) or placebo (n=277) once daily for up to 96 weeks. The primary end point was the skeletal morbidity period rate (SMPR), defined as the number of 12-week periods with new skeletal complications. Multivariate Poisson's regression analysis was used to assess the relative risk of skeletal-related events in each treatment group during the study period. Oral ibandronate 50 mg significantly reduced the mean SMPR compared with placebo (0.95 vs 1.18, P=0.004). There was a significant reduction in the mean number of events requiring radiotherapy (0.73 vs 0.98, P<0.001) and events requiring surgery (0.47 vs 0.53, P=0.037). Poisson's regression analysis confirmed that oral ibandronate significantly reduced the risk of a skeletal event compared with placebo (hazard ratio 0.62, 95% CI=0.48, 0.79; P=0.0001). The incidence of mild treatment-related upper GI AEs was slightly higher in the oral ibandronate 50 mg group compared with placebo, but very few serious drug-related AEs were reported. Oral ibandronate 50 mg is an effective, well-tolerated and convenient treatment for the prevention of skeletal complications of metastatic bone disease.
TL;DR: In this article, the authors improved Standard Big Bang Nucleosynthesis (SBBN) calculations taking into account new nuclear physics analyses (Descouvemont et al. 2003) using a Monte-Carlo technique, calculating the abundances of light nuclei versus the baryon to photon ratio.
Abstract: We improve Standard Big Bang Nucleosynthesis (SBBN) calculations taking into account new nuclear physics analyses (Descouvemont et al. 2003). Using a Monte-Carlo technique, we calculate the abundances of light nuclei versus the baryon to photon ratio.The results concerning omegab are compared to relevant astrophysical and cosmological observations. Consistency between WMAP, SBBN results and D/H data strengthens the deduced baryon density and has interesting consequences on cosmic chemical evolution. A significant discrepancy between the calculated Li-7 deduced from WMAP and the Spite plateau is clearly revealed. To explain this discrepancy three possibilities are invoked : uncertainties on the Li abundance, surface alteration of Li in the course of stellar evolution or poor knowledge of the reaction rates related to Be-7 destruction. In particular, the possible role of the up to now neglected Be-7(d,p)2He-4 and Be-7(d,alpha)Li5 reactions is considered. The impressive advances in CMB observations provide a strong motivation for more efforts in experimental nuclear physics and high quality spectroscopy to keep BBN in pace. Comment: accepted in ApJ, 22 pages, 5 figures
TL;DR: In this article, credit market imperfections, driven by microeconomic frictions and influenced by macroeconomic factors, could also be to blame for high unemployment, and the determination of equilibrium unemployment in the presence of credit market frictions both with exogenous and endogenous wages.
Abstract: Labour market frictions are not the only possible source of high unemployment. Credit market imperfections, driven by microeconomic frictions and influenced by macroeconomic factors, could also be to blame. To develop this idea in a simple and tractable macroeconomic model, we treat credit and labour market imperfections in a symmetrical way. Accordingly, we introduce specificity in credit relationships, and assume that credit to potential entrepreneurs is rationed due to endogenous search frictions, in the spirit of Diamond (1990). These imperfections mirror job search frictions in the labour market. We study the determination of equilibrium unemployment in the presence of credit market frictions both with exogenous and endogenous wages. We explore a number of possible extensions: endogenous destruction, monetary policy and the short-run effects of financial liberalization.
TL;DR: It is shown, using molecular phylogenies of two invertebrate and four vertebrate groups, that biotic interchange between these areas has been much more limited than hitherto assumed.
Abstract: The apparent biotic affinities between the mainland and the island in the Western Ghats-Sri Lanka biodiversity hotspot have been interpreted as the result of frequent migrations during recent periods of low sea level. We show, using molecular phylogenies of two invertebrate and four vertebrate groups, that biotic interchange between these areas has been much more limited than hitherto assumed. Despite several extended periods of land connection during the past 500,000 years, Sri Lanka has maintained a fauna that is largely distinct from that of the Indian mainland. Future conservation programs for the subcontinent should take into account such patterns of local endemism at the finest scale at which they may occur.
TL;DR: MRI is a reliable method of staging AP severity, has predictive value for the prognosis of the disease, and has fewer contraindications than CT.