A quantitative framework for characterizing the evolutionary history of mammalian gene expression

The evolutionary history of a gene helps predict its function and relationship to phenotypic traits. Although sequence conservation is commonly used to decipher gene function and assess medical relevance, methods for functional inference from comparative expression data are lacking. Here, we use RNA-seq across seven tissues from 17 mammalian species to show that expression evolution across mammals is accurately modeled by the Ornstein–Uhlenbeck process, a commonly proposed model of continuous trait evolution. We apply this model to identify expression pathways under neutral, stabilizing, and directional selection. We further demonstrate novel applications of this model to quantify the extent of stabilizing selection on a gene’s expression, parameterize the distribution of each gene’s optimal expression level, and detect deleterious expression levels in expression data from individual patients. Our work provides a statistical framework for interpreting expression data across species and in disease

The Case for a Muon Collider Higgs Factory

We propose the construction of a compact Muon Collider Higgs Factory. Such a machine can produce up to \sim 14,000 at 8\times 10^{31} cm^-2 sec^-1 clean Higgs events per year, enabling the most precise possible measurement of the mass, width and Higgs-Yukawa coupling constants.Comment: Supporting letter for the document: "Muon Collider Higgs Factory for Smowmass 2013", A White Paper submitted to the 2013 U.S. Community Summer Study of the Division of Particles and Fields of the American Physical Society, Y. Alexahin, et. al, FERMILAB-CONF-13-245-T (July, 2013

Computed Tomographic Measurements of Thigh Muscle Cross-Sectional Area and Attenuation Coefficient Predict Hip Fracture: The Health, Aging, and Body Composition Study

Fatty infiltration of muscle, myosteatosis, increases with age and results in reduced muscle strength and function and increased fall risk. However, it is unknown if increased fatty infiltration of muscle predisposes to hip fracture. We measured the mean Hounsfield unit (HU) of the lean tissue within the midthigh muscle bundle (thigh muscle HU, an indicator of intramuscular fat), its cross-sectional area (CSA, a measure of muscle mass) by computed tomography (CT), bone mineral density (BMD) of the hip and total-body percent fat by dual X-ray absorptiometry (DXA), isokinetic leg extensor strength, and the Short Physical Performance Battery (SPPB) in 2941 white and black women and men aged 70 to 79 years. Sixty-three hip fractures were validated during 6.6 years of follow-up. Proportional hazards regression analysis was used to assess the relative risk (RR) of hip fracture across variations in thigh muscle attenuation, CSA, muscle strength, and physical function for hip fracture. In models adjusted by age, race, gender, body mass index, and percentage fat, decreased thigh muscle HU resulted in increased risk of hip fracture [RR/SD = 1.58; 95% confidence interval (CI) 1.10–1.99], an association that continued to be significant after further adjustment for BMD. In models additionally adjusted by CSA, muscle strength, and SPPB score, decreased thigh muscle HU but none of the other muscle parameters continued to be associated with an increased risk of hip fracture (RR/SD = 1.42; 95% CI 1.03–1.97). Decreased thigh muscle HU, a measure of fatty infiltration of muscle, is associated with increased risk of hip fracture and appears to account for the association between reduced muscle strength, physical performance, and muscle mass and risk of hip fracture. This characteristic captures a physical characteristic of muscle tissue that may have importance in hip fracture etiology. © 2010 American Society for Bone and Mineral Researc

Spectroscopic characterization of CaNb2O6 single crystal doped with samarium ions

Spectroscopic measurements of the calcium niobate CaNb2O6 single crystal doped with samarium ions were performed. Polarized absorption and emission spectra as well as luminescence decay curves of this material were recorded as a function of temperature in the 5–300 K temperature region. Analysis of low temperature spectra made it possible to determine energies of crystal field components of Sm3+ multiplets involved in the excitation and luminescence phenomena. Number of crystal field levels derived implies that Sm3+ ions in the CaNb2O6 host are accommodated in several different sites. Radiative lifetime of the 4G5/2 metastable level determined based on the Judd–Ofelt analysis of room temperature absorption spectra amounts to 777 μs, a value close to that of luminescence lifetime determined from luminescence decay curve. Energy transfer between the NbO6 group and samarium ions was observed in wide temperature range. Intense luminescence related to the 4G5/2→6H7/2 and 4G5/2→6H9/2 transitions centered at 610 nm and 660 nm, respectively, combined with strong absorption band near 404 nm that matches perfectly the pump light provided by commercial InGaN/GaN diode lasers points at a potential of CaNb2O6:Sm3+ for the design of all-solid-state visible lasers

Effectiveness of dry needling on reducing pain intensity in patients with myofascial pain syndrome: a Meta-analysis

AbstractObjectiveTo summarize the literature about the effectiveness of dry needling (DN) on relieving pain and increasing range of motion (ROM) in individuals with myofascial pain syndrome (MPS).MethodsPapers published from January 2000 to January 2013 were identified through an electronic search in the databases MEDLINE, Dialnet, Cochrane Library Plus, Physiotherapy Evidence Database (PEDro) and Spanish Superior Council of Scientific Research (CSIC). The studies included were randomized controlled trials written in English and/or Spanish about the effectiveness of DN on pain and ROM in individuals with MPS.ResultsOut of 19 clinical trials that were potentially relevant, a total of 10 were included in the Meta-analysis. Regarding pain intensity reduction when measured before and immediately after the intervention, DN achieved improvement compared with the placebo treatment [d = − 0.49; 95% CI (− 3.21, 0.42)] and with the control group [d = − 9.13; 95% CI (− 14.70, − 3.56)]. However, other treatments achieved better results on the same variable compared with DN, considering the measurements for pre-treatment and immediately after [d = 2.54; 95% CI (− 0.40, 5.48)], as well as the pre-treatment and after 3-4 weeks [d = 4.23; 95% CI (0.78, 7.68)]. DN showed a significantly increased ROM when measured before the intervention and immediately after, in comparison with the placebo [d = 2.00; 95% CI (1.60, 2.41)]. However, other treatments achieved a significant better result regarding ROM when it was measured before the intervention and immediately after, as compared with DN [d = −1.42; 95% CI (− 1.84, − 0.99)].ConclusionDN was less effective on decreasing pain comparing to the placebo group. Other treatments were more effective than DN on reducing pain after 3-4 weeks. However, on increasing ROM, DN was more effective comparing to that of placebo group, but less than other treatments

Knowledge, attitude and practices of pediatricians regarding the prevention of oral diseases in Italy

BACKGROUND: Pediatricians are in an ideal position to advise families about the prevention and management of oral diseases in children. The objective of the study was to determine knowledge, attitude, and practices regarding the prevention of oral diseases among pediatricians in Italy. METHODS: A systematic random sample of 1000 pediatricians received a questionnaire on socio-demographic and practice characteristics; knowledge on risk factors; attitude and practices towards the prevention of oral diseases. RESULTS: A total of 507 pediatricians participated. More than half knew the main risk factors for oral diseases and this knowledge was higher in primary care pediatricians (p = 0.007), in those with a higher number of hours worked per week (p = 0.012), and who believed that oral diseases may be prevented (p = 0.017). Pediatricians with higher knowledge about the main risk factors (p = 0.006) believe that they have an important role in preventing oral diseases and that they can perform an oral examination. Almost all (89%) prescribed fluoride supplements and those younger (p = 0.016), with a higher number of patients seen in workday (p = 0.001), with longer practice activity (p = 0.004), those who believe that fluoride is effective in preventing caries (p < 0.0001), and who learned about prevention from scientific sources (p = 0.002) were more likely to prescribe fluoride. One-fourth and 40.6% provides and recommends a dental visit once a year and primary care pediatricians (p = 0.014) and those who believed that routine visit is important in preventing oral diseases (p < 0.0001) were more likely to recommend a dental visit once a year. CONCLUSION: The results showed a lack of knowledge among pediatricians although almost all believed that they had an important responsibility in preventing oral diseases and provided an oral examination

Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group

Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P&lt;5 × 10−8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis

BMI and Fracture Risk in Older Men: The Osteoporotic Fractures in Men Study (MrOS)

Low body mass index (BMI) is a risk factor for fracture, but little is known about the association between high BMI and fracture risk. We evaluated the association between BMI and fracture in the Osteoporotic Fractures in Men Study (MrOS), a cohort of 5995 US men 65 years of age and older. Standardized measures included weight, height, and hip bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA); medical history; lifestyle; and physical performance. Only 6 men (0.1%) were underweight (<18.5 kg/m2); therefore, men in this category were excluded. Also, 27% of men had normal BMI (18.5 to 24.9 kg/m2), 52% were overweight (25 to 29.9 kg/m2), 18% were obese I (30 to 34.9 kg/m2), and 3% were obese II (35 to 39.9 kg/m2). Overall, nonspine fracture incidence was 16.1 per 1000 person-years, and hip fracture incidence was 3.1 per 1000 person-years. In age-, race-, and BMD-adjusted models, compared with normal weight, the hazard ratio (HR) for nonspine fracture was 1.04 [95% confidence interval (CI) 0.87–1.25] for overweight, 1.29 (95% CI 1.00–1.67) for obese I, and 1.94 (95% CI 1.25–3.02) for obese II. Associations were weaker and not statistically significant after adjustment for mobility limitations and walking pace (HR = 1.02, 95% CI 0.84–1.23, for overweight; HR = 1.12, 95% CI 0.86–1.46, for obese I, and HR = 1.44, 95% CI 0.90–2.28, for obese II). Obesity is common among older men, and when BMD is held constant, it is associated with an increased risk of fracture. This association is at least partially explained by worse physical function in obese men. © 2011 American Society for Bone and Mineral Research

The updated spectral catalogue of INTEGRAL Gamma-Ray Bursts

We present a catalogue with the properties of all the bursts detected and localized by the IBIS instrument onboard the INTEGRAL satellite from November 2002 to September 2008. The sample is composed of 56 bursts, corresponding to a rate of ~ 0.8 GRB per month. Thanks to the performances of the INTEGRAL Burst Alert System, 50% of the IBIS GRBs have detected afterglows, while 5% have redshift measurements. A spectral analysis of the 43 bursts in the INTEGRAL public archive has been carried out using the most recent software and calibration, deriving an updated, homogeneous and accurate catalogue with the spectral features of the sample. When possible also a time-resolved spectral analysis has been carried out. The GRBs in the sample have 20-200 keV fluences in the range 5 x 1E-8 --2.5 x 1E-4 erg cm-2, and peak fluxes in the range 0.11 - 56 ph cm-2 s-1. While most of the spectra are well fitted by a power law with photon index ~ 1.6, we found that 9 bursts are better described by a cut-off power law, resulting in Ep values in the range 35--190 keV. Altough these results are comparable with those obtained with BAT onboard Swift, there is a marginal evidence that ISGRI detects dimmer bursts than Swift/BAT. Using the revised spectral parameters and an updated sky exposure map that takes into account also the effects of the GRB trigger efficiency, we strengthen the evidence for a spatial correlation with the super galactic plane of the faint bursts with long spectral lag (Foley et al.,2008).Comment: Corrected some typos, added some references; Accepted by Astronomy & Astrophysics, in pres