14 research outputs found
Non-commutative desingularization of determinantal varieties, I
We show that determinantal varieties defined by maximal minors of a generic
matrix have a non-commutative desingularization, in that we construct a maximal
Cohen-Macaulay module over such a variety whose endomorphism ring is
Cohen-Macaulay and has finite global dimension. In the case of the determinant
of a square matrix, this gives a non-commutative crepant resolution.Comment: 52 pages, 3 figures, all comments welcom
Mutation in triangulated categories and rigid Cohen-Macaulay modules
We introduce the notion of mutation of -cluster tilting subcategories in a
triangulated category with Auslander-Reiten-Serre duality. Using this idea, we
are able to obtain the complete classifications of rigid Cohen-Macaulay modules
over certain Veronese subrings.Comment: 52 pages. To appear in Invent. Mat
Stellar population synthesis at the resolution of 2003
We present a new model for computing the spectral evolution of stellar
populations at ages between 100,000 yr and 20 Gyr at a resolution of 3 A across
the whole wavelength range from 3200 to 9500 A for a wide range of
metallicities. These predictions are based on a newly available library of
observed stellar spectra. We also compute the spectral evolution across a
larger wavelength range, from 91 A to 160 micron, at lower resolution. The
model incorporates recent progress in stellar evolution theory and an
observationally motivated prescription for thermally-pulsing stars on the
asymptotic giant branch. The latter is supported by observations of surface
brightness fluctuations in nearby stellar populations. We show that this model
reproduces well the observed optical and near-infrared colour-magnitude
diagrams of Galactic star clusters of various ages and metallicities.
Stochastic fluctuations in the numbers of stars in different evolutionary
phases can account for the full range of observed integrated colours of star
clusters in the Magellanic Clouds. The model reproduces in detail typical
galaxy spectra from the Early Data Release (EDR) of the Sloan Digital Sky
Survey (SDSS). We exemplify how this type of spectral fit can constrain
physical parameters such as the star formation history, metallicity and dust
content of galaxies. Our model is the first to enable accurate studies of
absorption-line strengths in galaxies containing stars over the full range of
ages. Using the highest-quality spectra of the SDSS EDR, we show that this
model can reproduce simultaneously the observed strengths of those Lick indices
that do not depend strongly on element abundance ratios [abridged].Comment: 35 pages, 22 figures, to appear in MNRAS; version with full
resolution figures available at http://www.iap.fr/~charlot/bc2003/pape
Allan Sandage and the Cosmic Expansion
This is an account of Allan Sandage's work on (1) The character of the
expansion field. For many years he has been the strongest defender of an
expanding Universe. He later explained the CMB dipole by a local velocity of
220 +/- 50 km/s toward the Virgo cluster and by a bulk motion of the Local
supercluster (extending out to ~3500 km/s) of 450-500 km/s toward an apex at
l=275, b=12. Allowing for these streaming velocities he found linear expansion
to hold down to local scales (~300 km/s). (2) The calibration of the Hubble
constant. Probing different methods he finally adopted - from
Cepheid-calibrated SNe Ia and from independent RR Lyr-calibrated TRGBs - H_0 =
62.3 +/- 1.3 +/- 5.0 km/s/Mpc.Comment: 12 pages, 11 figures, 1 table, Submitted to Astrophysics and Space
Science, Special Issue on the Fundamental Cosmic Distance Scale in the Gaia
Er
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele
Sedimentary deposits left by the 2004 Indian Ocean tsunami on the inner continental shelf offshore of Khao Lak, Andaman Sea (Thailand)
Safety and efficacy of intravenous bimagrumab in inclusion body myositis (RESILIENT): a randomised, double-blind, placebo-controlled phase 2b trial
Background Inclusion body myositis is an idiopathic inflammatory myopathy and the most common myopathy affecting people older than 50 years. To date, there are no effective drug treatments. We aimed to assess the safety, efficacy, and tolerability of bimagrumab-a fully human monoclonal antibody-in individuals with inclusion body myositis.
Methods We did a multicentre, double-blind, placebo-controlled study (RESILIENT) at 38 academic clinical sites in Australia, Europe, Japan, and the USA. Individuals (aged 3685 years) were eligible for the study if they met modified 2010 Medical Research Council criteria for inclusion body myositis. We randomly assigned participants (1:1:1:1) using a blocked randomisation schedule (block size of four) to either bimagrumab (10 mg/kg, 3 mg/kg, or 1 mg/kg) or placebo matched in appearance to bimagrumab, administered as intravenous infusions every 4 weeks for at least 48 weeks. All study participants, the funder, investigators, site personnel, and people doing assessments were masked to treatment assignment. The primary outcome measure was 6-min walking distance (6MWD), which was assessed at week 52 in the primary analysis population and analysed by intention-to-treat principles. We used a multivariate normal repeated measures model to analyse data for 6MWD. Safety was assessed by recording adverse events and by electrocardiography, echocardiography, haematological testing, urinalysis, and blood chemistry. This trial is registered with ClinicalTrials.gov, number NCT01925209; this report represents the final analysis.
Findings Between Sept 26, 2013, and Jan 6, 2016, 251 participants were enrolled to the study, of whom 63 were assigned to each bimagrumab group and 62 were allocated to the placebo group. At week 52, 6MWD change from baseline did not differ between any bimagrumab dose and placebo (least squares mean treatment difference for bimagrumab 10 mg/kg group, 17.6 m, SE 14.3, 99% CI -19.6 to 54.8; p=0.22; for 3 mg/kg group, 18.6 m, 14.2, -18.2 to 55.4; p=0.19; and for 1 mg/kg group, 1.3 m, 14.1, -38.0 to 35.4; p=0.93). 63 (100%) participants in each bimagrumab group and 61 (98%) of 62 in the placebo group had at least one adverse event. Falls were the most frequent adverse event (48 [76%] in the bimagrumab 10 mg/kg group, 55 [87%] in the 3 mg/kg group, 54 [86%] in the 1 mg/kg group, and 52 [84%] in the placebo group). The most frequently reported adverse events with bimagrumab were muscle spasms (32 [51%] in the bimagrumab 10 mg/kg group, 43 [68%] in the 3 mg/kg group, 25 [40%] in the 1 mg/kg group, and 13 [21%] in the placebo group) and diarrhoea (33 [52%], 28 [44%], 20 [32%], and 11 [18%], respectively). Adverse events leading to discontinuation were reported in four (6%) participants in each bimagrumab group compared with one (2%) participant in the placebo group. At least one serious adverse event was reported by 21 (33%) participants in the 10 mg/kg group, 11 (17%) in the 3 mg/kg group, 20 (32%) in the 1 mg/kg group, and 20 (32%) in the placebo group. No significant adverse cardiac effects were recorded on electrocardiography or echocardiography. Two deaths were reported during the study, one attributable to subendocardial myocardial infarction (secondary to gastrointestinal bleeding after an intentional overdose of concomitant sedatives and antidepressants) and one attributable to lung adenocarcinoma. Neither death was considered by the investigator to be related to bimagrumab.
Interpretation Bimagrumab showed a good safety profile, relative to placebo, in individuals with inclusion body myositis but did not improve 6MWD. The strengths of our study are that, to the best of our knowledge, it is the largest randomised controlled trial done in people with inclusion body myositis, and it provides important natural history data over 12 months
Efficacy and safety of Bimagrumab in sporadic inclusion body myositis
Objective To assess long-term (2 years) effects of bimagrumab in participants with sporadic inclusion body myositis (sIBM).
Methods Participants (aged 36–85 years) who completed the core study (RESILIENT [Efficacy and Safety of Bimagrumab/BYM338 at 52 Weeks on Physical Function, Muscle Strength, Mobility in sIBM Patients]) were invited to join an extension study. Individuals continued on the same treatment as in the core study (10 mg/kg, 3 mg/kg, 1 mg/kg bimagrumab or matching placebo administered as IV infusions every 4 weeks). The co–primary outcome measures were 6-minute walk distance (6MWD) and safety.
Results Between November 2015 and February 2017, 211 participants entered double-blind placebo-controlled period of the extension study. Mean change in 6MWD from baseline was highly variable across treatment groups, but indicated progressive deterioration from weeks 24–104 in all treatment groups. Overall, 91.0% (n = 142) of participants in the pooled bimagrumab group and 89.1% (n = 49) in the placebo group had ≥1 treatment-emergent adverse event (AE). Falls were slightly higher in the bimagrumab 3 mg/kg group vs 10 mg/kg, 1 mg/kg, and placebo groups (69.2% [n = 36 of 52] vs 56.6% [n = 30 of 53], 58.8% [n = 30 of 51], and 61.8% [n = 34 of 55], respectively). The most frequently reported AEs in the pooled bimagrumab group were diarrhea 14.7% (n = 23), involuntary muscle contractions 9.6% (n = 15), and rash 5.1% (n = 8). Incidence of serious AEs was comparable between the pooled bimagrumab and the placebo group (18.6% [n = 29] vs 14.5% [n = 8], respectively).
Conclusion Extended treatment with bimagrumab up to 2 years produced a good safety profile and was well-tolerated, but did not provide clinical benefits in terms of improvement in mobility. The extension study was terminated early due to core study not meeting its primary endpoint