This book serves undergraduates, postgraduates, and scientists in materials science who wish to acquire or extend their understanding of ternary phase diagrams. Emphasis is given to the use of phase ...diagrams as a means of understanding phase changes that occur as a function of temperature.
Stromal cells are a subject of rapidly growing immunological interest based on their ability to influence virtually all aspects of innate and adaptive immunity. Present in every bodily tissue, ...stromal cells complement the functions of classical immune cells by sensing pathogens and tissue damage, coordinating leukocyte recruitment and function, and promoting immune response resolution and tissue repair. These diverse roles come with a price: like classical immune cells, inappropriate stromal cell behavior can lead to various forms of pathology, including inflammatory disease, tissue fibrosis, and cancer. An important immunological function of stromal cells is to act as information relays, responding to leukocyte-derived signals and instructing leukocyte behavior in kind. In this regard, several members of the interleukin-6 (IL-6) cytokine family, including IL-6, IL-11, oncostatin M (OSM), and leukemia inhibitory factor (LIF), have gained recognition as factors that mediate crosstalk between stromal and immune cells, with diverse roles in numerous inflammatory and homeostatic processes. This review summarizes our current understanding of how IL-6 family cytokines control stromal-immune crosstalk in health and disease, and how these interactions can be leveraged for clinical benefit.
We present the discovery by the WASP-South survey of WASP-121 b, a new remarkable short-period transiting hot Jupiter. The planet has a mass of
$1.183_{-0.062}^{+0.064}$
M
Jup, a radius of 1.865 ± ...0.044 R
Jup, and transits every
$1.274\,9255_{-0.000\,0025}^{+0.000\,0020}$
days an active F6-type main-sequence star (V = 10.4,
$1.353_{-0.079}^{+0.080}$
M⊙, 1.458 ± 0.030 R⊙, T
eff = 6460 ± 140 K). A notable property of WASP-121 b is that its orbital semimajor axis is only ∼1.15 times larger than its Roche limit, which suggests that the planet is close to tidal disruption. Furthermore, its large size and extreme irradiation (∼7.1 109 erg s−1 cm−2) make it an excellent target for atmospheric studies via secondary eclipse observations. Using the TRAnsiting Planets and PlanetesImals Small Telescope, we indeed detect its emission in the z
′-band at better than ∼4σ, the measured occultation depth being 603 ± 130 ppm. Finally, from a measurement of the Rossiter–McLaughlin effect with the CORALIE spectrograph, we infer a sky-projected spin-orbit angle of
$257{^{\circ}_{.}} 8_{-5{^{\circ}_{.}} 5}^{+5{^{\circ}_{.}} 3}$
. This result may suggest a significant misalignment between the spin axis of the host star and the orbital plane of the planet. If confirmed, this high misalignment would favour a migration of the planet involving strong dynamical events with a third body.
Abstract Background Many different measures of motivation to stop smoking exist but it would be desirable to have a brief version that is standard for use in population surveys and for evaluations of ...interventions to promote cessation. The aim of this study was to assess the predictive validity and accuracy of the single-item Motivation To Stop Scale (MTSS). Methods This study is part of the “Smoking Toolkit Study;” a monthly survey of representative samples of the English population. We used data from 2483 respondents to the surveys from November 2008 to January 2011, who were smokers, used the MTSS, and were followed up 6 months later to provide information on quit attempts since baseline. The MTSS consists of one item with seven response categories ranging from 1 (lowest) to level 7 (highest level of motivation to stop smoking). Results A total of 692 smokers (27.9% (95% CI = 26.1–29.6)) made an attempt to quit smoking between baseline and 6-month follow-up. The odds of quit attempts increased linearly with increasing level of motivation at baseline ( p < 0.001) and were 6.8 (95% CI = 4.7–9.9) times higher for the highest level of motivation compared with the lowest. The accuracy of the MTSS for discriminating between smokers who did and did not attempt to quit was ROCAUC = 0.67 (95% CI = 0.65–0.70). Conclusions The MTSS provides strong and accurate prediction of quit attempts and is a candidate for a standard single-item measure of motivation to stop smoking. Further research should assess the external validity of this measure in different smoking populations.
The diagnosis of autism spectrum disorder (ASD) at the earliest age possible is important for initiating optimally effective intervention. In the United States the average age of diagnosis is 4 ...years. Identifying metabolic biomarker signatures of ASD from blood samples offers an opportunity for development of diagnostic tests for detection of ASD at an early age.
To discover metabolic features present in plasma samples that can discriminate children with ASD from typically developing (TD) children. The ultimate goal is to identify and develop blood-based ASD biomarkers that can be validated in larger clinical trials and deployed to guide individualized therapy and treatment.
Blood plasma was obtained from children aged 4 to 6, 52 with ASD and 30 age-matched TD children. Samples were analyzed using 5 mass spectrometry-based methods designed to orthogonally measure a broad range of metabolites. Univariate, multivariate and machine learning methods were used to develop models to rank the importance of features that could distinguish ASD from TD.
A set of 179 statistically significant features resulting from univariate analysis were used for multivariate modeling. Subsets of these features properly classified the ASD and TD samples in the 61-sample training set with average accuracies of 84% and 86%, and with a maximum accuracy of 81% in an independent 21-sample validation set.
This analysis of blood plasma metabolites resulted in the discovery of biomarkers that may be valuable in the diagnosis of young children with ASD. The results will form the basis for additional discovery and validation research for 1) determining biomarkers to develop diagnostic tests to detect ASD earlier and improve patient outcomes, 2) gaining new insight into the biochemical mechanisms of various subtypes of ASD 3) identifying biomolecular targets for new modes of therapy, and 4) providing the basis for individualized treatment recommendations.
Objective
To assess the long‐term safety and 16‐week efficacy of subcutaneous tanezumab in patients with hip or knee osteoarthritis (OA).
Methods
This was a phase III randomized, double‐blind, active ...treatment–controlled (using nonsteroidal antiinflammatory drugs NSAIDs as the active treatment control) safety trial of tanezumab (56‐week treatment/24‐week posttreatment follow‐up) in adults who were receiving stable‐dose NSAID therapy at the time of screening and who had Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function scores of ≥5; patient global assessment (PtGA) of OA of fair, poor, or very poor; history of inadequate pain relief with standard analgesics; and no history or radiographic evidence of prespecified bone/joint conditions beyond OA. Patients received oral naproxen, celecoxib, or diclofenac twice daily (NSAID group; n = 996) or tanezumab 2.5 mg (n = 1,002) or 5 mg (n = 998) subcutaneously every 8 weeks. Coprimary efficacy end points at week 16 were changes in WOMAC pain and physical function scores and changes in PtGA. The primary joint safety end point over 80 weeks comprised adjudicated rapidly progressive OA type 1 or 2, primary osteonecrosis, subchondral insufficiency fracture, or pathologic fracture. Mean values, least squares mean values, and least squares mean differences between groups (with 95% confidence intervals 95% CIs) were calculated.
Results
Of 3,021 randomized patients, 2,996 received ≥1 treatment dose. Adverse events (AEs) were similar between patients treated with tanezumab 2.5 mg and those treated with NSAIDs, and were more prevalent in those treated with tanezumab 5 mg. Composite joint safety events were significantly more prevalent with tanezumab 2.5 mg and tanezumab 5 mg than with NSAIDs (observation time–adjusted rate/1,000 patient‐years 38.3 95% CI 28.0, 52.5 and 71.5 95% CI 56.7, 90.2, respectively, versus 14.8 95% CI 8.9, 24.6; P = 0.001 for tanezumab 2.5 mg versus NSAIDs; P < 0.001 for tanezumab 5 mg versus NSAIDs). Tanezumab 5 mg significantly improved pain and physical function but did not improve PtGA at week 16 when compared to NSAIDs; corresponding differences between the tanezumab 2.5 mg and NSAID groups were not statistically significant.
Conclusion
In patients previously receiving a stable dose of NSAIDs, tanezumab administered subcutaneously resulted in more joint safety events than continued NSAIDs, with differences being dose dependent. Pain and physical function improved with both doses of tanezumab compared to NSAIDs, reaching statistical significance with tanezumab 5 mg at 16 weeks.
Although there is evidence that liquids have flowed on the surface at Titan's equator in the past, to date, liquids have only been confirmed on the surface at polar latitudes, and the vast expanses ...of dunes that dominate Titan's equatorial regions require a predominantly arid climate. We report the detection by Cassini's Imaging Science Subsystem of a large low-latitude cloud system early in Titan's northern spring and extensive surface changes (spanning more than 500,000 square kilometers) in the wake of this storm. The changes are most consistent with widespread methane rainfall reaching the surface, which suggests that the dry channels observed at Titan's low latitudes are carved by seasonal precipitation.
Fluorescence in situ hybridization (FISH) reveals the abundance and positioning of nucleic acid sequences in fixed samples. Despite recent advances in multiplexed amplification of FISH signals, it ...remains challenging to achieve high levels of simultaneous amplification and sequential detection with high sampling efficiency and simple workflows. Here we introduce signal amplification by exchange reaction (SABER), which endows oligonucleotide-based FISH probes with long, single-stranded DNA concatemers that aggregate a multitude of short complementary fluorescent imager strands. We show that SABER amplified RNA and DNA FISH signals (5- to 450-fold) in fixed cells and tissues. We also applied 17 orthogonal amplifiers against chromosomal targets simultaneously and detected mRNAs with high efficiency. We then used 10-plex SABER-FISH to identify in vivo introduced enhancers with cell-type-specific activity in the mouse retina. SABER represents a simple and versatile molecular toolkit for rapid and cost-effective multiplexed imaging of nucleic acid targets.
Objective: Smokers from more deprived socioeconomic groups are less likely to become ex-smokers. This study examined how far this is attributable in England to a social gradient in quit attempts, use ...of aids to cessation and/or the success of quit attempts. Design: Cross-sectional household survey. Setting: England. Participants: 6950 respondents aged 16+ who had smoked in the past year, of whom 2983 had tried to stop in the past year and 469 reported having stopped at the time of the survey. Main outcome measures: Reported attempts to stop smoking in the past year; the use of stop-smoking medications (nicotine replacement therapy, bupropion or varenicline); use of behavioural support offered by the National Health Service Stop Smoking Services; current smoking status. Results: There was a large difference in success rates of quit attempts: 20.4% in social grade AB versus 11.4% in social grade E of those who made attempts were still not smoking by the time of the survey (p<0.001). However, there was no difference across social grades in the rate of attempts to stop (42.7% in social grade AB to 41.3% in E), use of medications to aid cessation (46.7% of those making quit attempts in AB to 50.9% in E) or use of NHS Stop Smoking Services (7.0% of those making quit attempts in AB to 4.8% in E). Conclusions: Smokers in more deprived socioeconomic groups are just as likely as those in higher groups to try to stop and use aids to cessation but there is a strong gradient across socioeconomic groups in success, with those in the lowest group being half as likely to succeed compared with the highest. Determining the cause of, and counteracting, this gradient is paramount in reducing health inequalities.
We report on the discovery of WASP-12b, a new transiting extrasolar planet with R pl = 1.79+0.09 -0.09 RJ and M pl = 1.41+0.10 -0.10 M J. The planet and host star properties were derived from a Monte ...Carlo Markov Chain analysis of the transit photometry and radial velocity data. Furthermore, by comparing the stellar spectrum with theoretical spectra and stellar evolution models, we determined that the host star is a supersolar metallicity (M/H = 0.3+0.05 -0.15), late-F (T eff = 6300+200 -100 K) star which is evolving off the zero-age main sequence. The planet has an equilibrium temperature of T eq = 2516 K caused by its very short period orbit (P = 1.09 days) around the hot, twelfth magnitude host star. WASP-12b has the largest radius of any transiting planet yet detected. It is also the most heavily irradiated and the shortest period planet in the literature.
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