OMCat: Catalogue of Serendipitous Sources Detected with the XMM-Newton Optical Monitor

The Optical Monitor Catalogue of serendipitous sources (OMCat) contains entries for every source detected in the publicly available XMM-Newton Optical Monitor (OM) images taken in either the imaging or ``fast'' modes. Since the OM is coaligned and records data simultaneously with the X-ray telescopes on XMM-Newton, it typically produces images in one or more near-UV/optical bands for every pointing of the observatory. As of the beginning of 2006, the public archive had covered roughly 0.5% of the sky in 2950 fields. The OMCat is not dominated by sources previously undetected at other wavelengths; the bulk of objects have optical counterparts. However, the OMCat can be used to extend optical or X-ray spectral energy distributions for known objects into the ultraviolet, to study at higher angular resolution objects detected with GALEX, or to find high-Galactic-latitude objects of interest for UV spectroscopy.Comment: 25 pages, 22 figures, submitted to PAS

Using the XMM Optical Monitor to Study Cluster Galaxy Evolution

We explore the application of XMM-Newton Optical Monitor (XMM-OM) ultraviolet (UV) data to study galaxy evolution. Our sample is constructed as the intersection of all Abell clusters with z < 0.05 and having archival XMM-OM data in either the UVM2 or UVW1 filters, plus optical and UV photometry from the Sloan Digital Sky Survey and GALEX, respectively. The eleven resulting clusters include 726 galaxies with measured redshifts, 520 of which have redshifts placing them within their parent Abell clusters. We develop procedures for manipulating the XMM-OM images and measuring galaxy photometry from them, and confirm our results via comparison with published catalogs. Color magnitude diagrams (CMDs) constructed using the XMM-OM data along with SDSS optical data show promise for evolutionary studies, with good separation between red and blue sequences and real variation in the width of the red sequence that is likely indicative of differences in star formation history. This is particularly true for UVW1 data, as the relative abundance of data collected using this filter and its depth make it an attractive choice. Available tools that use stellar synthesis libraries to fit the UV and optical photometric data may also be used, thereby better describing star formation history within the past Gyr and providing estimates of total stellar mass that include contributions from young stars. Finally, color-color diagrams that include XMM-OM UV data appear useful to the photometric identification of both extragalactic and stellar sources.Comment: 44 pages with 14 figures, to appear in PAS

Location of acute coronary artery thromboses in patients with and without chronic kidney disease

Patients with chronic kidney disease have high rates of myocardial infarction and death following an initial attack. Proximal location of coronary atherosclerotic lesions has been linked to the risk of acute myocardial infarction and to infarction-associated mortality. To examine if the spatial distribution of lesions differs in patients with and without chronic kidney disease, we used quantitative coronary angiography to measure this in patients with acute coronary thromboses who were having angiography following acute myocardial infarction. Multivariable linear regression was used to adjust for differences in baseline characteristics. Among 82 patients with stage 3 or higher chronic kidney disease, 55.6% of lesions were located within 30 mm and 87.7% were within 50 mm of the coronary ostia. This compared to 34.7 and 71.8%, respectively, among 299 patients without significant kidney disease. Chronic kidney disease was independently and significantly associated with a 7.0 mm decrease in the distance from the coronary ostia to the problem lesion. Our study suggests that a causal link between a more proximal culprit lesion location in patients with chronic kidney disease and their high mortality rates after myocardial infarct is possible and may have important implications for interventions to prevent infarction

Treatment algorithm for infants diagnosed with spinal muscular atrophy through newborn screening

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by the degeneration of alpha motor neurons in the spinal cord, leading to muscular atrophy. SMA is caused by deletions or mutations in the survival motor neuron 1 gene (SMN1). In humans, a nearly identical copy gene, SMN2, is present. Because SMN2 has been shown to decrease disease severity in a dose-dependent manner, SMN2 copy number is predictive of disease severity. To develop a treatment algorithm for SMA-positive infants identified through newborn screening based upon SMN2 copy number. A working group comprised of 15 SMA experts participated in a modified Delphi process, moderated by a neutral third-party expert, to develop treatment guidelines. The overarching recommendation is that all infants with two or three copies of SMN2 should receive immediate treatment (n = 13). For those infants in which immediate treatment is not recommended, guidelines were developed that outline the timing and appropriate screens and tests to be used to determine the timing of treatment initiation. The identification SMA affected infants via newborn screening presents an unprecedented opportunity for achievement of maximal therapeutic benefit through the administration of treatment pre-symptomatically. The recommendations provided here are intended to help formulate treatment guidelines for infants who test positive during the newborn screening process

XMM-Newton Observations of MBM 12: More Constraints on the Solar Wind Charge Exchange and Local Bubble Emissions

We present the first analysis of an XMM-Newton observation of the nearby molecular cloud MBM 12. We find that in the direction of MBM 12 the total O VII (0.57 keV) triplet emission is 1.8(+0.5/-0.6) photons/sq cm/s/sr (or Line Units - LU) while for the O VIII (0.65 keV) line emission we find a 3(sigma) upper limit of <1 LU. We also use a heliospheric model to calculate the O VII and O VIII emission generated by Solar Wind Charge-eXchange (SWCX) which we compare to the XMM-Newton observations. This comparison provides new constraints on the relative heliospheric and Local Bubble contributions to the local diffuse X-ray background. The heliospheric SWCX model predicts 0.82 LU for O VII, which accounts for approx. 46+/-15% of the observed value, and 0.33 LU for the O VIII line emission consistent with the XMM-Newton observed value. We discuss our results in combination with previous observations of the MBM 12 with CHANDRA and Suzaku

Restoration of Nusinersen Levels Following Treatment Interruption in People With Spinal Muscular Atrophy: Simulations Based on a Population Pharmacokinetic Model

Background: Nusinersen is approved for the treatment of spinal muscular atrophy. The most common approved dosing regimen is four intrathecal loading doses of nusinersen 12 mg; the first three are administered at 14-day intervals followed by a fourth dose 30 days later, and then 12-mg maintenance doses are administered every 4 months thereafter. Interruption of nusinersen treatment in the maintenance dosing phase might occur for a number of clinical reasons. / Objective: The objective of this report is to describe dosing regimens that allow for the most rapid restoration of steady-state concentrations of nusinersen in the cerebrospinal fluid (CSF) following a treatment interruption during maintenance dosing. / Methods: Population pharmacokinetic models using integrated pharmacokinetic data from ten nusinersen clinical trials that included a broad range of participants with spinal muscular atrophy treated with intrathecal nusinersen were used to investigate different durations of treatment interruptions during maintenance treatment. Potential dosing regimens for re-initiation of nusinersen were evaluated, with the goal of achieving the quickest restoration of steady-state nusinersen CSF concentrations without exceeding maximal CSF exposures observed during the initial loading period. / Results: Our pharmacokinetic modeling indicates the following regimen will lead to optimal restoration of nusinersen CSF levels after treatment interruption: two doses of nusinersen should be administered at 14-day intervals following treatment interruptions of ≥ 8 to < 16 months since the last dose, and three doses of nusinersen at 14-day intervals for treatment interruptions of ≥ 16 to < 40 months since the last maintenance dose, with subsequent maintenance dosing every 4 months in both instances. After treatment interruptions of ≥ 40 months, the full loading regimen will rapidly restore nusinersen CSF levels. / Conclusions: Prolonged treatment interruptions lead to suboptimal CSF levels of nusinersen. The optimal regimen to restore nusinersen CSF levels depends on the interval since the last maintenance dose was administered

Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis.

The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP) were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V) were identified in the analysis of 92 familial ALS patients (3.3%), while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis

Preintervention arterial remodeling affects clinical outcome following stenting: an intravascular ultrasound study

AbstractOBJECTIVESThe study was done to elucidate the relationship between baseline arterial remodeling and clinical outcome following stenting.BACKGROUNDThe impact of preintervention arterial remodeling on subsequent vessel response and clinical outcome has been reported following nonstent coronary interventions. However, in stented segments, the impact of preintervention remodeling on clinical outcome has not been clarified.METHODSPreintervention remodeling was assessed in 108 native coronary lesions by using intravascular ultrasound (IVUS). Positive remodeling (PR) was defined as vessel area (VA) at the target lesion greater than that of average reference segments. Intermediate or negative remodeling (IR/NR) was defined as VA at the target lesion less than or equal to that of average reference segment. Remodeling index expressed as a continuous variable was defined as VA at the target lesion site divided by that of average reference segments.RESULTSPositive remodeling was present in 59 (55%) and IR/NR in 49 (45%) lesions. Although final minimal stent areas were similar (7.76 ± 1.80 vs. 8.09 ± 1.90 mm2, p = 0.36), target vessel revascularization (TVR) rate at nine-month follow-up was significantly higher in the PR group (22.0% vs. 4.1%, p = 0.01). By multivariate logistic regression analysis, higher remodeling index was the only independent predictor of TVR (p = 0.02).CONCLUSIONSLesions with PR before intervention appear to have a worse clinical outcome following IVUS-guided stenting. Intravascular ultrasound imaging before stenting may be helpful to stratify lesions at high risk for accelerated intimal proliferation