337 research outputs found
Automated SNP detection from a large collection of white spruce expressed sequences: contributing factors and approaches for the categorization of SNPs
BACKGROUND: High-throughput genotyping technologies represent a highly efficient way to accelerate genetic mapping and enable association studies. As a first step toward this goal, we aimed to develop a resource of candidate Single Nucleotide Polymorphisms (SNP) in white spruce (Picea glauca [Moench] Voss), a softwood tree of major economic importance. RESULTS: A white spruce SNP resource encompassing 12,264 SNPs was constructed from a set of 6,459 contigs derived from Expressed Sequence Tags (EST) and by using the bayesian-based statistical software PolyBayes. Several parameters influencing the SNP prediction were analysed including the a priori expected polymorphism, the probability score (P(SNP)), and the contig depth and length. SNP detection in 3' and 5' reads from the same clones revealed a level of inconsistency between overlapping sequences as low as 1%. A subset of 245 predicted SNPs were verified through the independent resequencing of genomic DNA of a genotype also used to prepare cDNA libraries. The validation rate reached a maximum of 85% for SNPs predicted with either P(SNP )≥ 0.95 or ≥ 0.99. A total of 9,310 SNPs were detected by using P(SNP )≥ 0.95 as a criterion. The SNPs were distributed among 3,590 contigs encompassing an array of broad functional categories, with an overall frequency of 1 SNP per 700 nucleotide sites. Experimental and statistical approaches were used to evaluate the proportion of paralogous SNPs, with estimates in the range of 8 to 12%. The 3,789 coding SNPs identified through coding region annotation and ORF prediction, were distributed into 39% nonsynonymous and 61% synonymous substitutions. Overall, there were 0.9 SNP per 1,000 nonsynonymous sites and 5.2 SNPs per 1,000 synonymous sites, for a genome-wide nonsynonymous to synonymous substitution rate ratio (Ka/Ks) of 0.17. CONCLUSION: We integrated the SNP data in the ForestTreeDB database along with functional annotations to provide a tool facilitating the choice of candidate genes for mapping purposes or association studies
Frequency and characteristics of disease flares in ankylosing spondylitis
Objective. To examine the characteristics and frequency of disease flares in a cohort of people with AS
Broad white matter impairment in multiple system atrophy.
Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by the widespread aberrant accumulation of α-synuclein (α-syn). MSA differs from other synucleinopathies such as Parkinson's disease (PD) in that α-syn accumulates primarily in oligodendrocytes, the only source of white matter myelination in the brain. Previous MSA imaging studies have uncovered focal differences in white matter. Here, we sought to build on this work by taking a global perspective on whole brain white matter. In order to do this, in vivo structural imaging and diffusion magnetic resonance imaging were acquired on 26 MSA patients, 26 healthy controls, and 23 PD patients. A refined whole brain approach encompassing the major fiber tracts and the superficial white matter located at the boundary of the cortical mantle was applied. The primary observation was that MSA but not PD patients had whole brain deep and superficial white matter diffusivity abnormalities (p < .001). In addition, in MSA patients, these abnormalities were associated with motor (Unified MSA Rating Scale, Part II) and cognitive functions (Mini-Mental State Examination). The pervasive whole brain abnormalities we observe suggest that there is widespread white matter damage in MSA patients which mirrors the widespread aggregation of α-syn in oligodendrocytes. Importantly, whole brain white matter abnormalities were associated with clinical symptoms, suggesting that white matter impairment may be more central to MSA than previously thought
NectarCAM : a camera for the medium size telescopes of the Cherenkov Telescope Array
NectarCAM is a camera proposed for the medium-sized telescopes of the
Cherenkov Telescope Array (CTA) covering the central energy range of ~100 GeV
to ~30 TeV. It has a modular design and is based on the NECTAr chip, at the
heart of which is a GHz sampling Switched Capacitor Array and a 12-bit Analog
to Digital converter. The camera will be equipped with 265 7-photomultiplier
modules, covering a field of view of 8 degrees. Each module includes the
photomultiplier bases, high voltage supply, pre-amplifier, trigger, readout and
Ethernet transceiver. The recorded events last between a few nanoseconds and
tens of nanoseconds. The camera trigger will be flexible so as to minimize the
read-out dead-time of the NECTAr chips. NectarCAM is designed to sustain a data
rate of more than 4 kHz with less than 5\% dead time. The camera concept, the
design and tests of the various subcomponents and results of thermal and
electrical prototypes are presented. The design includes the mechanical
structure, cooling of the electronics, read-out, clock distribution, slow
control, data-acquisition, triggering, monitoring and services.Comment: In Proceedings of the 34th International Cosmic Ray Conference
(ICRC2015), The Hague, The Netherlands. All CTA contributions at
arXiv:1508.0589
Novel image–novel location object recognition task sensitive to age-related cognitive decline in nondemented elderly
Traditional tests used in the clinic to identify dementia, such as the mini-mental state examination (MMSE), are useful to identify severe cognitive impairments but might be less sensitive to detect more subtle age-related cognitive changes. Previously, the novel image–novel location (NINL) object recognition test was shown to be sensitive to detect effects of apolipoprotein E4, a risk factor for developing age-related cognitive decline and Alzheimer’s disease, in nondemented elderly. In the present longitudinal study, performance on the MMSE and the NINL tests were compared over a 4-year period. Individual NINL scores over this period were highly correlated. In addition, while MMSE scores did not change over the 4-year period, NINL scores did. In a final testing session of a subset of the participants, NINL scores correlated with logical memory and word recall lists, cognitive tasks used to detect dementia in the clinic, as well as clinical dementia rating scales. These results support that the NINL might be a valuable tool to assess age-related cognitive decline
Shower development of particles with momenta from 15 GeV to 150 GeV in the CALICE scintillator-tungsten hadronic calorimeter
We present a study of showers initiated by electrons, pions, kaons, and
protons with momenta from 15 GeV to 150 GeV in the highly granular CALICE
scintillator-tungsten analogue hadronic calorimeter. The data were recorded at
the CERN Super Proton Synchrotron in 2011. The analysis includes measurements
of the calorimeter response to each particle type as well as measurements of
the energy resolution and studies of the longitudinal and radial shower
development for selected particles. The results are compared to Geant4
simulations (version 9.6.p02). In the study of the energy resolution we include
previously published data with beam momenta from 1 GeV to 10 GeV recorded at
the CERN Proton Synchrotron in 2010.Comment: 35 pages, 21 figures, 8 table
Longitudinal Numbers-Needed-To-Treat (NNT) for Achieving Various Levels of Analgesic Response and Improvement with Etoricoxib, Naproxen, and Placebo in Ankylosing Spondylitis
<p>Abstract</p> <p>Background</p> <p>Clinical analgesic trials typically report response as group mean results. However, research has shown that few patients are average and most have responses at the extremes. Moreover, group mean results do not convey response levels and thus have limited value in representing the benefit-risk at an individual level. Responder analyses and numbers-needed-to-treat (NNT) are considered more relevant for evaluating treatment response. We evaluated levels of analgesic response and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score improvement and the associated NNTs.</p> <p>Methods</p> <p>This was a post-hoc analysis of a 6-week, randomized, double-blind study (N = 387) comparing etoricoxib 90 mg, etoricoxib 120 mg, naproxen 1000 mg, and placebo in AS. Spine pain and BASDAI were measured on a 100-mm visual analog scale. The number and percentage of patients achieving ≥30% and ≥50% improvement in both BASDAI and spine pain were calculated and used to determine the corresponding NNTs. Patients who discontinued from the study for any reason were assigned zero improvement beyond 7 days of the time of discontinuation.</p> <p>Results</p> <p>For etoricoxib 90 mg, etoricoxib 120 mg and naproxen 1000 mg, the NNTs at 6 weeks compared with placebo were 2.0, 2.0, and 2.7 respectively for BASDAI ≥30% improvement, and 3.2, 2.8, and 4.1 for ≥50% improvement. For spine pain, the NNTs were 1.9, 2.0, and 3.2, respectively, for ≥30% improvement, and 2.7, 2.5, and 3.7 for ≥50% improvement. The differences between etoricoxib and naproxen exceeded the limit of ±0.5 units described as a clinically meaningful difference for pain. Response rates and NNTs were generally similar and stable over 2, 4, and 6 weeks.</p> <p>Conclusions</p> <p>For every 2 patients treated with etoricoxib, 1 achieved a clinically meaningful (≥30%) improvement in spine pain and BASDAI beyond that expected from placebo, whereas the corresponding values were approximately 1 in every 3 patients treated with naproxen. Use of NNTs and responder analyses provide additional, complementary information beyond population mean responses when assessing efficacy compared to placebo and amongst active therapies.</p
Development and Feasibility of a Smartphone, ECG and GPS Based System for Remotely Monitoring Exercise in Cardiac Rehabilitation
Background Despite its efficacy and cost-effectiveness, exercise-based cardiac rehabilitation is undertaken by less than one-third of clinically eligible cardiac patients in every country for which data is available. Reasons for non-participation include the unavailability of hospital-based rehabilitation programs, or excessive travel time and distance. For this reason, there have been calls for the development of more flexible alternatives. Methodology and Principal Findings We developed a system to enable walking-based cardiac rehabilitation in which the patient's single-lead ECG, heart rate, GPS-based speed and location are transmitted by a programmed smartphone to a secure server for real-time monitoring by a qualified exercise scientist. The feasibility of this approach was evaluated in 134 remotely-monitored exercise assessment and exercise sessions in cardiac patients unable to undertake hospital-based rehabilitation. Completion rates, rates of technical problems, detection of ECG changes, pre- and post-intervention six minute walk test (6 MWT), cardiac depression and Quality of Life (QOL) were key measures. The system was rated as easy and quick to use. It allowed participants to complete six weeks of exercise-based rehabilitation near their homes, worksites, or when travelling. The majority of sessions were completed without any technical problems, although periodic signal loss in areas of poor coverage was an occasional limitation. Several exercise and post-exercise ECG changes were detected. Participants showed improvements comparable to those reported for hospital-based programs, walking significantly further on the post-intervention 6 MWT, 637 m (95% CI: 565–726), than on the pre-test, 524 m (95% CI: 420–655), and reporting significantly reduced levels of cardiac depression and significantly improved physical health-related QOL. Conclusions and Significance The system provided a feasible and very flexible alternative form of supervised cardiac rehabilitation for those unable to access hospital-based programs, with the potential to address a well-recognised deficiency in health care provision in many countries. Future research should assess its longer-term efficacy, cost-effectiveness and safety in larger samples representing the spectrum of cardiac morbidity and severity
Hadron shower decomposition in the highly granular CALICE analogue hadron calorimeter
The spatial development of hadronic showers in the CALICE scintillator-steel
analogue hadron calorimeter is studied using test beam data collected at CERN
and FNAL for single positive pions and protons with initial momenta in the
range from 10 to 80 GeV/c. Both longitudinal and radial development of hadron
showers are parametrised with two-component functions. The parametrisation is
fit to test beam data and simulations using the QGSP_BERT and FTFP_BERT physics
lists from Geant4 version 9.6. The parameters extracted from data and simulated
samples are compared for the two types of hadrons. The response to pions and
the ratio of the non-electromagnetic to the electromagnetic calorimeter
response, h/e, are estimated using the extrapolation and decomposition of the
longitudinal profiles.Comment: 38 pages, 19 figures, 5 tables; author list changed; submitted to
JINS
- …