236 research outputs found
Maximum Likelihood Estimator for Hidden Markov Models in continuous time
The paper studies large sample asymptotic properties of the Maximum
Likelihood Estimator (MLE) for the parameter of a continuous time Markov chain,
observed in white noise. Using the method of weak convergence of likelihoods
due to I.Ibragimov and R.Khasminskii, consistency, asymptotic normality and
convergence of moments are established for MLE under certain strong ergodicity
conditions of the chain.Comment: Warning: due to a flaw in the publishing process, some of the
references in the published version of the article are confuse
H5N1 Influenza Vaccine Formulated with AS03A Induces Strong Cross-Reactive and Polyfunctional CD4 T-Cell Responses
Objective Adjuvantation of an H5N1 split-virion influenza vaccine with AS03(A) substantially reduces the antigen dose required to produce a putatively protective humoral response and promotes cross-clade neutralizing responses. We determined the effect of adjuvantation on antibody persistence and B- and T-cell-mediated immune responses.
Methods Two vaccinations with a split-virion A/Vietnam/1194/2004 (H5N1, clade 1) vaccine containing 3.75-30 mu g hemagglutinin and formulated with or without adjuvant were administered to groups of 50 volunteers aged 18-60 years.
Results Adjuvantation of the vaccine led to better persistence of neutralizing and hemagglutination-inhibiting antibodies and higher frequencies of antigen-specific memory B cells. Cross-reactive and polyfunctional H5N1-specific CD4 T cells were detected at baseline and were amplified by vaccination. Expansion of CD4 T cells was enhanced by adjuvantation.
Conclusion Formulation of the H5N1 vaccine with AS03(A) enhances antibody persistence and induces stronger T- and B-cell responses. The cross-clade T-cell immunity indicates that the adjuvanted vaccine primes individuals to respond to either infection and/or subsequent vaccination with strains drifted from the primary vaccine strain
Broad Clade 2 Cross-Reactive Immunity Induced by an Adjuvanted Clade 1 rH5N1 Pandemic Influenza Vaccine
The availability of H5N1 vaccines that can elicit a broad cross-protective immunity against different currently circulating clade 2 H5N1 viruses is a pre-requisite for the development of a successful pre-pandemic vaccination strategy. In this regard, it has recently been shown that adjuvantation of a recombinant clade 1 H5N1 inactivated split-virion vaccine with an oil-in-water emulsion-based adjuvant system also promoted cross-immunity against a recent clade 2 H5N1 isolate (A/Indonesia/5/2005, subclade 2.1). Here we further analyse the cross-protective potential of the vaccine against two other recent clade 2 isolates (A/turkey/Turkey/1/2005 and A/Anhui/1/2005 which are, as defined by WHO, representatives of subclades 2.2 and 2.3 respectively).Two doses of the recombinant A/Vietnam/1194/2004 (H5N1, clade 1) vaccine were administered 21 days apart to volunteers aged 18-60 years. We studied the cross-clade immunogenicity of the lowest antigen dose (3.8 microg haemagglutinin) given with (N = 20) or without adjuvant (N = 20). Immune responses were assessed at 21 days following the first and second vaccine doses and at 6 months following first vaccination. Vaccination with two doses of 3.8 microg of the adjuvanted vaccine induced four-fold neutralising seroconversion rates in 85% of subjects against A/turkey/Turkey/1/2005 (subclade 2.2) and 75% of subjects against A/Anhui/1/2005 (subclade 2.3) recombinant strains. There was no response induced against these strains in the non-adjuvanted group. At 6 months following vaccination, 70% and 60% of subjects retained neutralising antibodies against the recombinant subclade 2.2 and 2.3 strains, respectively and 40% of subjects retained antibodies against the recombinant subclade 2.1 A/Indonesia/5/2005 strain.In addition to antigen dose-sparing, adjuvantation of inactivated split H5N1 vaccine promotes broad and persistent cross-clade immunity which is a pre-requisite for a pre-pandemic vaccine.ClinicalTrials.gov NCT00309634
Giant phonon anomalies and central peak due to charge density wave formation in YBaCuO
The electron-phonon interaction is a major factor influencing the competition
between collective instabilities in correlated-electron materials, but its role
in driving high-temperature superconductivity in the cuprates remains poorly
understood. We have used high-resolution inelastic x-ray scattering to monitor
low-energy phonons in YBaCuO (superconducting
K), which is close to a charge density wave (CDW) instability. Phonons in a
narrow range of momentum space around the CDW ordering vector exhibit extremely
large superconductivity-induced lineshape renormalizations. These results imply
that the electron-phonon interaction has sufficient strength to generate
various anomalies in electronic spectra, but does not contribute significantly
to Cooper pairing. In addition, a quasi-elastic "central peak" due to CDW
nanodomains is observed in a wide temperature range above and below ,
suggesting that the gradual onset of a spatially inhomogeneous CDW domain state
with decreasing temperature is a generic feature of the underdoped cuprates
Infraspinatus scapular retraction test: a reliable and practical method to assess infraspinatus strength in overhead athletes with scapular dyskinesis
Background Alteration of normal scapulohumeral rhythm due to the fatigue of scapular-stabilizing muscles induces decrease of rotator cuff strength. In this study we analyzed the interobserver and intraobserver realibility of the infraspinatus strength test (IST) and infraspinatus scapular retraction test (ISRT) in 29 overhead athletes with scapular dykinesis, before and after 6 months of scapular musculature rehabilitation. Materials and methods Subjects with magnetic resonance imaging (MRI) findings of labral injuries (2 cases, 5%) and cuff tears (4 cases, 11%) were excluded. Scapular dyskinesis patterns were evaluated according to Kibler et al. (J Shoulder Elbow Surg 11:550-556, 2002). We found a type I dyskinesis in 24 cases (83%) and a type II in 5 cases (17%). Patients were tested by using IST and ISRT and the maximum infraspinatus strength (kg) was registered by a handheld dynamometer. Changes in shoulder IR were measured by using a standard goniometry. Rehabilitation continued for 6 months and was focused on the restoration of scapular muscular control and balance. We used a paired Student t test for the significance of the force values (alpha = 0.01). Intraclass correlation coefficient (ICC) and standard error (SE) were applied to determine the realibility of repeated values collected within testers and between testers. Results Values of ICC close to 1 at baseline and at 6 months indicated a higher interexaminer and intraexaminer realibility. IST force values registered a significant increase at 6 months for both examiners (P<0.01). The mean difference between IST and ISRT values were not significant at 6 months (P>0.01). The increase of glenohumeral internal rotation was significant at 6 months (P<0.01). Conclusion The good realibility and the easy reproducibility make the ISRT an excellent test to assess patients with infraspinatus weakness due to scapular dyskinesis and address them toward an appropriate program of rehabilitation aimed to restore scapular musculature balance and control. \ua9 The Author(s) 2010
Effects of tendon transfer to restore index finger abduction for severe cubital tunnel syndrome
A genome scan for milk production traits in dairy goats reveals two new mutations in <i>Dgat1</i> reducing milk fat content
The quantity of milk and milk fat and proteins are particularly important traits in dairy livestock.
However, little is known about the regions of the genome that influence these traits in goats. We
conducted a genome wide association study in French goats and identified 109 regions associated
with dairy traits. For a major region on chromosome 14 closely associated with fat content, the
Diacylglycerol O-Acyltransferase 1 (DGAT1) gene turned out to be a functional and positional candidate
gene. The caprine reference sequence of this gene was completed and 29 polymorphisms were found in
the gene sequence, including two novel exonic mutations: R251L and R396W, leading to substitutions
in the protein sequence. The R251L mutation was found in the Saanen breed at a frequency of 3.5% and
the R396W mutation both in the Saanen and Alpine breeds at a frequencies of 13% and 7% respectively.
The R396W mutation explained 46% of the genetic variance of the trait, and the R251L mutation 6%.
Both mutations were associated with a notable decrease in milk fat content. Their causality was then
demonstrated by a functional test. These results provide new knowledge on the genetic basis of milk
synthesis and will help improve the management of the French dairy goat breeding program
Pressure-temperature evolution of primordial solar system solids during impact-induced compaction
Prior to becoming chondritic meteorites, primordial solids were a poorly consolidated mix of mm-scale igneous inclusions (chondrules) and high-porosity sub-ÎŒm dust (matrix). We used high-resolution numerical simulations to track the effect of impact-induced compaction on these materials. Here we show that impact velocities as low as 1.5âkmâsâ1 were capable of heating the matrix to >1,000âK, with pressureâtemperature varying by >10âGPa and >1,000âK over ~100âÎŒm. Chondrules were unaffected, acting as heat-sinks: matrix temperature excursions were brief. As impact-induced compaction was a primary and ubiquitous process, our new understanding of its effects requires that key aspects of the chondrite record be re-evaluated: palaeomagnetism, petrography and variability in shock level across meteorite groups. Our data suggest a lithification mechanism for meteorites, and provide a âspeed limitâ constraint on major compressive impacts that is inconsistent with recent models of solar system orbital architecture that require an early, rapid phase of main-belt collisional evolution
Radiation therapy for epithelial ovarian cancer brain metastases: clinical outcomes and predictors of survival
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