ABSTRACT
We searched for an isotropic stochastic gravitational wave background in the second data release of the International Pulsar Timing Array, a global collaboration synthesizing decadal-length ...pulsar-timing campaigns in North America, Europe, and Australia. In our reference search for a power-law strain spectrum of the form $h_c = A(f/1\, \mathrm{yr}^{-1})^{\alpha }$, we found strong evidence for a spectrally similar low-frequency stochastic process of amplitude $A = 3.8^{+6.3}_{-2.5}\times 10^{-15}$ and spectral index α = −0.5 ± 0.5, where the uncertainties represent 95 per cent credible regions, using information from the auto- and cross-correlation terms between the pulsars in the array. For a spectral index of α = −2/3, as expected from a population of inspiralling supermassive black hole binaries, the recovered amplitude is $A = 2.8^{+1.2}_{-0.8}\times 10^{-15}$. None the less, no significant evidence of the Hellings–Downs correlations that would indicate a gravitational-wave origin was found. We also analysed the constituent data from the individual pulsar timing arrays in a consistent way, and clearly demonstrate that the combined international data set is more sensitive. Furthermore, we demonstrate that this combined data set produces comparable constraints to recent single-array data sets which have more data than the constituent parts of the combination. Future international data releases will deliver increased sensitivity to gravitational wave radiation, and significantly increase the detection probability.
In this study, three different carbon fillers (Thermocarb TC-300 synthetic graphite, Ketjenblack EC-600 JD carbon black, and Hyperion Catalysis International's FIBRILtrade mark sign carbon nanotubes) ...were added to a polypropylene matrix to produce single filler composites with filler concentrations of up to 80 wt % synthetic graphite (61.6 vol %), 15 wt % carbon black (8.1 vol %), and 15 wt % carbon nanotubes (7.4 vol %). The through-plane thermal conductivity for each formulation was measured. For the synthetic graphite, carbon black, and carbon nanotubes composites, the Nielsen model was applied to the experimental through-plane thermal conductivity data. The Nielsen Model presented in this work showed very good agreement with experimental data. The model parameters were similar to those used in the literature for these fillers in other polymers.
Describes the optimisation of an imidazole amide series, leading to the identification of (
S)-
15b (AZD5597) as a candidate for further development.
The development of a novel series of imidazole ...pyrimidine amides as cyclin-dependent kinase (CDK) inhibitors is described. Optimisation of inhibitory potency against multiple CDK’s (1, 2 and 9) resulted in imidazole pyrimidine amides with potent in vitro anti-proliferative effects against a range of cancer cell lines. Excellent physiochemical properties and large margins against inhibition of CYP isoforms and the hERG ion channel were achieved by modification of lipophilicity and amine basicity. A candidate with disease model activity in human cancer cell line xenografts and with suitable physiochemical and pharmacokinetic profiles for intravenous (iv) dosing was selected for further development as AZD5597.
The optimisation of a series of glucokinase activators is described, including attempts to uncouple the relationship between potency and plasma protein binding, and to better understand the key ...pharmacokinetic properties of the series. The use of unbound clearance as an optimisation parameter facilitated the identification of GKA50, a compound which combines excellent potency and pharmacokinetics with good free drug levels and solubility, and exhibits in vivo efficacy at 1mg/kg po in an acute rat OGTT model.
The continued discovery of a novel series of pyridine acid containing glucokinase activators is described. The composite parameter of unbound clearance was used to aid in the identification of
GKA60, ...a potent, soluble glucokinase activator with excellent bioavailability and increased half-life.
The continued optimization of a series of glucokinase activators is described, including attempts to understand the interplay between molecular structure and the composite parameter of unbound clearance. These studies resulted in the discovery of a new scaffold for glucokinase activators and further exploration of this scaffold led to the identification of
GKA60.
GKA60 maintains an excellent balance of potency and physical properties whilst possessing a significantly different, but complimentary, pre-clinical pharmacokinetic profile compared with the previously disclosed compound
GKA50.
Abstract
We present 294 pulsars found in GeV data from the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope. Another 33 millisecond pulsars (MSPs) discovered in deep radio searches ...of LAT sources will likely reveal pulsations once phase-connected rotation ephemerides are achieved. A further dozen optical and/or X-ray binary systems colocated with LAT sources also likely harbor gamma-ray MSPs. This catalog thus reports roughly 340 gamma-ray pulsars and candidates, 10% of all known pulsars, compared to ≤11 known before Fermi. Half of the gamma-ray pulsars are young. Of these, the half that are undetected in radio have a broader Galactic latitude distribution than the young radio-loud pulsars. The others are MSPs, with six undetected in radio. Overall, ≥236 are bright enough above 50 MeV to fit the pulse profile, the energy spectrum, or both. For the common two-peaked profiles, the gamma-ray peak closest to the magnetic pole crossing generally has a softer spectrum. The spectral energy distributions tend to narrow as the spindown power
E
̇
decreases to its observed minimum near 10
33
erg s
−1
, approaching the shape for synchrotron radiation from monoenergetic electrons. We calculate gamma-ray luminosities when distances are available. Our all-sky gamma-ray sensitivity map is useful for population syntheses. The electronic catalog version provides gamma-ray pulsar ephemerides, properties, and fit results to guide and be compared with modeling results.
Almost half of young children in the United States live in poverty or near poverty. The American Academy of Pediatrics is committed to reducing and ultimately eliminating child poverty in the United ...States. Poverty and related social determinants of health can lead to adverse health outcomes in childhood and across the life course, negatively affecting physical health, socioemotional development, and educational achievement. The American Academy of Pediatrics advocates for programs and policies that have been shown to improve the quality of life and health outcomes for children and families living in poverty. With an awareness and understanding of the effects of poverty on children, pediatricians and other pediatric health practitioners in a family-centered medical home can assess the financial stability of families, link families to resources, and coordinate care with community partners. Further research, advocacy, and continuing education will improve the ability of pediatricians to address the social determinants of health when caring for children who live in poverty. Accompanying this policy statement is a technical report that describes current knowledge on child poverty and the mechanisms by which poverty influences the health and well-being of children.
ABSTRACT
The International Pulsar Timing Array 2nd data release is the combination of data sets from worldwide collaborations. In this study, we search for continuous waves: gravitational wave ...signals produced by individual supermassive black hole binaries in the local universe. We consider binaries on circular orbits and neglect the evolution of orbital frequency over the observational span. We find no evidence for such signals and set sky averaged 95 per cent upper limits on their amplitude h95. The most sensitive frequency is 10 nHz with h95 = 9.1 × 10−15. We achieved the best upper limit to date at low and high frequencies of the PTA band thanks to improved effective cadence of observations. In our analysis, we have taken into account the recently discovered common red noise process, which has an impact at low frequencies. We also find that the peculiar noise features present in some pulsars data must be taken into account to reduce the false alarm. We show that using custom noise models is essential in searching for continuous gravitational wave signals and setting the upper limit.
The forest floor in many ecosystems consists of a partially decomposed organic layer (duff), which together with the litter layer comprises the boundary between the atmosphere and the mineral soil. ...Processes controlling the duff water budget during dry periods (which occur during most of the summer) were investigated using field monitoring, field flow exclusion manipulations, and coupled, multiphasic water and heat budget modeling. The objective of this paper is to model the significant processes that govern the dynamics of the duff water budget during drying. During dry periods the moisture content of the duff's F layer cycles diurnally with minimal moisture movement between the duff and mineral soil. Field exclusion of dew, lateral flow, and mineral soil flow suggests that diurnal drying cycles during the dry period are driven by diurnal atmospheric energy fluxes leading to coupled heat and mass fluxes within the duff. The fine root system and lateral flow do not typically influence drying. TOUGH2 was used to develop a one‐dimensional, multiphasic (both liquid and vapor) coupled water and heat budget model which confirmed that the vertical moisture fluxes lead to diurnal cycles. The model reproduced duff drying patterns with Nash‐Sutcliffe efficiencies and R2 values greater than 0.910 and 0.970, respectively. Wavelet analysis indicates that the model and observed diurnal cycles in the upper layer's moisture contents are correlated at the 24 h scale. A model flux analysis reveals that lateral fluxes smaller than approximately 360 mm3 h−1 would have little influence on the pattern of drying in the duff layer. Fluxes larger than approximately 5% of the total evaporative flux would slow duff drying and lead to behavior not observed in the field.
Background:
The glenohumeral joint combines large range of motion and insufficient bony stabilization, making it susceptible to instability and dislocations. Arthroscopic surgery is routinely used as ...a diagnostic tool and has been considered the gold standard for the diagnosis of shoulder lesions. However, several studies have demonstrated variability in intraobserver and interobserver agreement.
Purpose:
To evaluate interobserver and intraobserver agreement in the assessment of intra-articular lesions associated with shoulder instability among fellowship-trained shoulder surgeons.
Study Design:
Cohort study (diagnosis); Level of evidence, 3.
Methods:
A total of 24 arthroscopic videos from patients treated for recurrent shoulder instability were shown to a group of 10 fellowship-trained shoulder surgeons who are members of the Multicenter Orthopaedic Outcomes Network (MOON) Shoulder Group. They were presented to the surgeons on 2 different occasions at least 2 months apart. They were asked to classify labral tears by their position, type, extension, other intra-articular abnormality, and preferred treatment. No patient history or physical examination data were provided. The primary outcome was the median overall percentage of agreement for the surgeons performing a video review, measured for each variable evaluated. Intraclass correlation coefficients were used to evaluate continuous variables, and kappa values were used for categorical items.
Results:
Interobserver agreement was good for anterior labral lesions; good for Hill-Sachs lesions; and moderate for lesions of the superior labrum, posterior labrum, anterior sublabral foramen, and position and extension of the tear. Intraobserver agreement was either good or very good for all variables evaluated, except for being poor for inferior labral lesions and moderate for lesions of the meniscoid superior labrum.
Conclusion:
Interobserver and intraobserver reliability for the arthroscopic assessment of labral tears in patients with recurrent shoulder instability were good to moderate for the majority of anatomic structures assessed. There was relatively good agreement between shoulder instability surgeons on assessing and documenting shoulder instability–associated abnormalities. These findings are important when interpreting collaborative clinical cohort studies with numerous surgeons involved in the research.
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