151 research outputs found
A phase 3 multicenter, prospective, open-label efficacy and safety study of immune globulin (human) 10% caprylate/chromatography purified in patients with myasthenia gravis exacerbations
Background: Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular transmission. Exacerbations may involve increasing bulbar weakness and/or sudden respiratory failure, both of which can be critically disabling. Management of MG exacerbations includes plasma exchange and intravenous immunoglobulin (IVIG); they are equally effective, but patients experience fewer side effects with IVIG. The objective of this study was to assess the efficacy and safety of immune globulin caprylate/chromatography purified (IGIV-C) in subjects with MG exacerbations. Methods: This prospective, open-label, non-controlled 28-day clinical trial was conducted in adults with MG Foundation of America class IVb or V status. Subjects received IGIV-C 2 g/kg over 2 consecutive days (1 g/kg/day) and were assessed for efficacy/safety on Days 7, 14, 21, and 28. The primary efficacy endpoint was the change from Baseline in quantitative MG (QMG) score to Day 14. Secondary endpoints of clinical response, Baseline to Day 14, included at least a 3-point decrease in QMG and MG Composite and a 2-point decrease in MG-activities of daily living (MG-ADL). Results: Forty-nine subjects enrolled. The change in QMG score at Day 14 was significant (p < 0.001) in the Evaluable (-6.4, n = 43) and Safety (-6.7, n = 49) populations. Among evaluable subjects, Day 14 response rates were 77, 86, and 88% for QMG, MG Composite, and MG-ADL, respectively. IGIV-C showed good tolerability with no serious adverse events. Conclusions: The results of this study show that IGIV-C was effective, safe, and well tolerated in the treatment of MG exacerbations
Prehistory of Transit Searches
Nowadays the more powerful method to detect extrasolar planets is the transit
method. We review the planet transits which were anticipated, searched, and the
first ones which were observed all through history. Indeed transits of planets
in front of their star were first investigated and studied in the solar system.
The first observations of sunspots were sometimes mistaken for transits of
unknown planets. The first scientific observation and study of a transit in the
solar system was the observation of Mercury transit by Pierre Gassendi in 1631.
Because observations of Venus transits could give a way to determine the
distance Sun-Earth, transits of Venus were overwhelmingly observed. Some
objects which actually do not exist were searched by their hypothetical
transits on the Sun, as some examples a Venus satellite and an infra-mercurial
planet. We evoke the possibly first use of the hypothesis of an exoplanet
transit to explain some periodic variations of the luminosity of a star, namely
the star Algol, during the eighteen century. Then we review the predictions of
detection of exoplanets by their transits, those predictions being sometimes
ancient, and made by astronomers as well as popular science writers. However,
these very interesting predictions were never published in peer-reviewed
journals specialized in astronomical discoveries and results. A possible
transit of the planet beta Pic b was observed in 1981. Shall we see another
transit expected for the same planet during 2018? Today, some studies of
transits which are connected to hypothetical extraterrestrial civilisations are
published in astronomical refereed journals. Some studies which would be
classified not long ago as science fiction are now considered as scientific
ones.Comment: Submiited to Handbook of Exoplanets (Springer
Dusty Planetary Systems
Extensive photometric stellar surveys show that many main sequence stars show
emission at infrared and longer wavelengths that is in excess of the stellar
photosphere; this emission is thought to arise from circumstellar dust. The
presence of dust disks is confirmed by spatially resolved imaging at infrared
to millimeter wavelengths (tracing the dust thermal emission), and at optical
to near infrared wavelengths (tracing the dust scattered light). Because the
expected lifetime of these dust particles is much shorter than the age of the
stars (>10 Myr), it is inferred that this solid material not primordial, i.e.
the remaining from the placental cloud of gas and dust where the star was born,
but instead is replenished by dust-producing planetesimals. These planetesimals
are analogous to the asteroids, comets and Kuiper Belt objects (KBOs) in our
Solar system that produce the interplanetary dust that gives rise to the
zodiacal light (tracing the inner component of the Solar system debris disk).
The presence of these "debris disks" around stars with a wide range of masses,
luminosities, and metallicities, with and without binary companions, is
evidence that planetesimal formation is a robust process that can take place
under a wide range of conditions. This chapter is divided in two parts. Part I
discusses how the study of the Solar system debris disk and the study of debris
disks around other stars can help us learn about the formation, evolution and
diversity of planetary systems by shedding light on the frequency and timing of
planetesimal formation, the location and physical properties of the
planetesimals, the presence of long-period planets, and the dynamical and
collisional evolution of the system. Part II reviews the physical processes
that affect dust particles in the gas-free environment of a debris disk and
their effect on the dust particle size and spatial distribution.Comment: 68 pages, 25 figures. To be published in "Solar and Planetary
Systems" (P. Kalas and L. French, Eds.), Volume 3 of the series "Planets,
Stars and Stellar Systems" (T.D. Oswalt, Editor-in-chief), Springer 201
Debris Disks: Probing Planet Formation
Debris disks are the dust disks found around ~20% of nearby main sequence
stars in far-IR surveys. They can be considered as descendants of
protoplanetary disks or components of planetary systems, providing valuable
information on circumstellar disk evolution and the outcome of planet
formation. The debris disk population can be explained by the steady
collisional erosion of planetesimal belts; population models constrain where
(10-100au) and in what quantity (>1Mearth) planetesimals (>10km in size)
typically form in protoplanetary disks. Gas is now seen long into the debris
disk phase. Some of this is secondary implying planetesimals have a Solar
System comet-like composition, but some systems may retain primordial gas.
Ongoing planet formation processes are invoked for some debris disks, such as
the continued growth of dwarf planets in an unstirred disk, or the growth of
terrestrial planets through giant impacts. Planets imprint structure on debris
disks in many ways; images of gaps, clumps, warps, eccentricities and other
disk asymmetries, are readily explained by planets at >>5au. Hot dust in the
region planets are commonly found (<5au) is seen for a growing number of stars.
This dust usually originates in an outer belt (e.g., from exocomets), although
an asteroid belt or recent collision is sometimes inferred.Comment: Invited review, accepted for publication in the 'Handbook of
Exoplanets', eds. H.J. Deeg and J.A. Belmonte, Springer (2018
Circumstellar disks and planets. Science cases for next-generation optical/infrared long-baseline interferometers
We present a review of the interplay between the evolution of circumstellar
disks and the formation of planets, both from the perspective of theoretical
models and dedicated observations. Based on this, we identify and discuss
fundamental questions concerning the formation and evolution of circumstellar
disks and planets which can be addressed in the near future with optical and
infrared long-baseline interferometers. Furthermore, the importance of
complementary observations with long-baseline (sub)millimeter interferometers
and high-sensitivity infrared observatories is outlined.Comment: 83 pages; Accepted for publication in "Astronomy and Astrophysics
Review"; The final publication is available at http://www.springerlink.co
Successful radiation treatment of anaplastic thyroid carcinoma metastatic to the right cardiac atrium and ventricle in a pacemaker-dependent patient
Anaplastic thyroid carcinoma (ATC) is a rare, aggressive malignancy, which is known to metastasize to the heart. We report a case of a patient with ATC with metastatic involvement of the pacemaker leads within the right atrium and right ventricle. The patient survived external beam radiation treatment to his heart, with a radiographic response to treatment. Cardiac metastases are usually reported on autopsy; to our knowledge, this is the first report of the successful treatment of cardiac metastases encasing the leads of a pacemaker, and of cardiac metastases from ATCs, with a review of the pertinent literature
Second malignant neoplasms after a first cancer in childhood: temporal pattern of risk according to type of treatment
The variation in the risk of solid second malignant neoplasms (SMN) with time since first cancer during childhood has been previously reported. However, no study has been performed that controls for the distribution of radiation dose and the aggressiveness of past chemotherapy, which could be responsible for the observed temporal variation of the risk. The purpose of this study was to investigate the influence of the treatment on the long-term pattern of the incidence of solid SMN after a first cancer in childhood. We studied a cohort of 4400 patients from eight centres in France and the UK. Patients had to be alive 3 years or more after a first cancer treated before the age of 17 years and before the end of 1985. For each patient in the cohort, the complete clinical, chemotherapy and radiotherapy history was recorded. For each patient who had received external radiotherapy, the dose of radiation received by 151 sites of the body were estimated. After a mean follow-up of 15 years, 113 children developed a solid SMN, compared to 12.3 expected from general population rates. A similar distribution pattern was observed among the 1045 patients treated with radiotherapy alone and the 2064 patients treated with radiotherapy plus chemotherapy; the relative risk, but not the excess absolute risk, of solid SMN decreased with time after first treatment; the excess absolute risk increased during a period of at least 30 years after the first cancer. This pattern remained after controlling for chemotherapy and for the average dose of radiation to the major sites of SMN. It also remained when excluding patients with a first cancer type or an associated syndrome known to predispose to SMN. When compared with radiotherapy alone, the addition of chemotherapy increases the risk of solid SMN after a first cancer in childhood, but does not significantly modify the variation of this risk during the time after the first cancer. © 1999 Cancer Research Campaig
IP-10 response to RD1 antigens might be a useful biomarker for monitoring tuberculosis therapy
Background
There is an urgent need of prognosis markers for tuberculosis (TB) to improve treatment strategies. The results of several studies show that the Interferon (IFN)-γ-specific response to the TB antigens of the QuantiFERON TB Gold (QFT-IT antigens) decreases after successful TB therapy. The objective of this study was to evaluate whether there are factors other than IFN-γ [such as IFN-γ inducible protein (IP)-10 which has also been associated with TB] in response to QFT-IT antigens that can be used as biomarkers for monitoring TB treatment.
Methods
In this exploratory study we assessed the changes in IP-10 secretion in response to QFT-IT antigens and RD1 peptides selected by computational analysis in 17 patients with active TB at the time of diagnosis and after 6 months of treatment. The IFN-γ response to QFT-IT antigens and RD1 selected peptides was evaluated as a control. A non-parametric Wilcoxon signed-rank test for paired comparisons was used to compare the continuous variables at the time of diagnosis and at therapy completion. A Chi-square test was used to compare proportions.
Results
We did not observe significant IP-10 changes in whole blood from either NIL or QFT-IT antigen tubes, after 1-day stimulation, between baseline and therapy completion (p = 0.08 and p = 0.7 respectively). Conversely, the level of IP-10 release to RD1 selected peptides was significantly different (p = 0.006). Similar results were obtained when we detected the IFN-γ in response to the QFT-IT antigens (p = 0.06) and RD1 selected peptides (p = 0.0003). The proportion of the IP-10 responders to the QFT-IT antigens did not significantly change between baseline and therapy completion (p = 0.6), whereas it significantly changed in response to RD1 selected peptides (p = 0.002). The proportion of IFN-γ responders between baseline and therapy completion was not significant for QFT-IT antigens (p = 0.2), whereas it was significant for the RD1 selected peptides (p = 0.002), confirming previous observations.
Conclusions
Our preliminary study provides an interesting hypothesis: IP-10 response to RD1 selected peptides (similar to IFN-γ) might be a useful biomarker for monitoring therapy efficacy in patients with active TB. However, further studies in larger cohorts are needed to confirm the consistency of these study results
Timbre from Sound Synthesis and High-level Control Perspectives
International audienceExploring the many surprising facets of timbre through sound manipulations has been a common practice among composers and instrument makers of all times. The digital era radically changed the approach to sounds thanks to the unlimited possibilities offered by computers that made it possible to investigate sounds without physical constraints. In this chapter we describe investigations on timbre based on the analysis by synthesis approach that consists in using digital synthesis algorithms to reproduce sounds and further modify the parameters of the algorithms to investigate their perceptual relevance. In the first part of the chapter timbre is investigated in a musical context. An examination of the sound quality of different wood species for xylophone making is first presented. Then the influence of instrumental control on timbre is described in the case of clarinet and cello performances. In the second part of the chapter, we mainly focus on the identification of sound morphologies, so called invariant sound structures responsible for the evocations induced by environmental sounds by relating basic signal descriptors and timbre descriptors to evocations in the case of car door noises, motor noises, solid objects, and their interactions
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